António João Ferreira de Macedo e Santos é médico psiquiatra nos hospitais da universidade de coimbra e professor auxiliar agregado de psicologia médica na faculdade de medicina da universidade de coimbra . É ainda professor afiliado da faculdade de medicina do porto. É regente de diversas unidades curriculares relacionadas com a psicologia médica e comunicação médico-doente. Áreas de investigação principais: genética da esquizofrenia e doença bipolar; perturbações do espectro obsessivo; doença afectiva; personalidade e sua relação com a psicopatologia. Tem 2 livros publicados, 5 capítulos de livros, cerca de 60 artigos em revistas internacionais , 62 artigos em actas de congressos internacionais e 50 artigos em revistas nacionais. António João Ferreira de Macedo Santos is a psychiatrist at the University Hospitall of Coimbra and assistant professor of medical psychology in the medical school of the University of Coimbra. he is also a affiliated professor at the medical school of the Oporto University. He is head of the department of medical psychology and teaches several courses related to medical psychology and doctor-patient communication. Main research areas: genetics of schizophrenia and bipolar disorder, obsessive spectrum disorders, affective illness, personality and its relationship to psychopathology. It has two published books, five book chapters, about 60 papers in international journals, 62 articles in proceedings of international conferences and 50 papers in national journals
Endereço de acesso a este CV: http://www.degois.pt/visualizador/curriculum.jsp?key=8099091358609199

Nome completo Full name	António João Ferreira de Macedo e Santos
Nome em citações bibliográficas Quoting name	Macedo, A.

Endereço profissional Professional address

Universidade de Coimbra Faculdade de Medicina Instituto de Psicologia Médica Rua Larga Coimbra 3004 Coimbra Portugal Telefone: (+351)239857759 Correio electrónico: amacedo@ci.uc.pt

Sexo Gender

Masculino»Male

2006	Agregação Aggregation
Universidade de Coimbra, Portugal.

1994-1998	Doutoramento Phd
neuropsiquiatria. Universidade de Coimbra, Portugal.

1979-1985	Licenciatura Licentiate degree
medicina (6 anos » years) . Universidade de Coimbra, Portugal.

Compreende Understandig	Inglês (Bem), Francês (Bem).
Fala Speaking	Inglês (Bem), Francês (Bem).
Lê Reading	Inglês (Bem), Francês (Bem).
Escreve Writing	Inglês (Bem), Francês (Bem).

2006	PRÉMIO MELHOR COMUNICAÇÃO ORAL Annual Meeting of the Associação de Psiquiatria Biológica Attention-Deficit Hyperactivity Disorder Across The Life Span, Associação de Psiquiatria Biológica.
2007	MELHOR POSTER III Congresso Nacional de Psiquiatria, Sociedade Portuguesa de Psiquiatria e Saúde Mental.
2009	MELHOR POSTER VII Simposium de Perturbações Afectivas, Universidade do Minho, Universidade do Minho.
2009	2º MELHOR POSTER V Congresso da Sociedade Portuguesa de Psiquiatria e Saúde Mental, Porto, Sociedade Portuguesa de Psiquiatria e Saúde Mental.
2010	MENÇÃO HONROSA (2) 8as Jornadas sobre Comportamentos Suicidários, Sociedade Portuguesa de Suicidologia.

Livros publicados/organizados ou edições Published/organized books or Editions

1.	Macedo, A.; Pocinho, F.. 2007. Obsessões e Compulsões: As multiplas faces de uma doença (2ª. Edição). ed. 2, 1 vol., ISBN: 978-989-558-088-0. Coimbra: Quarteto. OBSESSÕES E COMPULSÕES (2ª. Edição): O Distúrbio Obsessivo-Compulsivo é uma entidade nosológica que continua a suscitar grande curiosidade clínica, pela complexidade e polimorfismo das suas manifestações. Na vertente da investigação neurobiológica, é uma enfermidade que também tem evocado um interesse crescente. O conhecimento e compreensão dos mecanismos e processos que estão envolvidos na sua causalidade, quer de natureza biológica, quer de natureza psicológica revestem-se de particular importância na procura de melhores formas de tratamento. Esta é uma condição clínica cujo tratamento não é fácil, representando um desafio para terapeutas e doentes. Porventura, será uma das perturbações psiquiátricas em que a relação colaborativa entre o doente e o terapeuta é mais crucial, constituindo um factor decisivo no êxito terapêutico. Esta é uma das mensagens que também queremos transmitir aos doentes e famílias: é possível tratar com sucesso este tipo de problemas. A investigação que temos desenvolvido na área do perfeccionismo e da sua relação com os distúrbios do espectro obsessivo, leva-nos a incluir um novo capítulo sobre essa relevante e interessante temática. .

2.	Macedo, A.; Azevedo, M. H. P. 2001. Os Genes que pensam. ed. 1, ISBN: 9789728717056. Coimbra: Quarteto. OS GENES QUE PENSAM O psiquiatra do século XXI deverá continuar a ser o que sempre foi, um terapeuta que empaticamente toma a seu cargo o alívio do sofrimento psicológico dos seus doentes. A par dessa função, deverá simultaneamente ser um cientista que necessita dominar um conhecimento biológico interdisciplinar, proveniente de várias áreas das neurociências. Neste sentido, o desenvolvimento da genética, como um dos alicerces mais promissores da medicina em geral, terá também nas doenças mentais, profundas repercussões em múltiplas vertentes, desde o diagnóstico e terapêutica ao aconselhamento genético. Pensamos que este livro pode contribuir para a formação de várias classes de profissionais ligados à saúde, particularmente aqueles que lidam com os problemas da saúde mental, tais como médicos internos de psiquiatria e psiquiatras, enfermeiros e psicólogos. Tendo esta obra prioritariamente um fim didáctico, alguns capítulos são de carácter mais genérico. Neles se procura dar uma perspectiva mais alargada das metodologias e questões conceptuais envolvidas na investigação genética. Outros capítulos são mais específicos e versam temas que dizem respeito à esquizofrenia, distúrbio afectivo bipolar e outras doenças neuropsiquiátricas.

3.	Macedo, A.; Pocinho, F.. 2000. Obsessões e Compulsões: As múltiplas faces de uma doença (1ª. Edição). ed. 1, 1 vol., ISBN: 972-8535-30. Coimbra: Quarteto. OBSESSÕES E COMPULSÕES (1ª. Edição): Aspectos como a evolução histórica do conceito, a definição, a epidemiologia, as formas das manifestações clínicas, os factores causais, a genética, os factores de bom e de mau prognóstico, a relação com outros quadros clínicos que também pertencem ao espectro obsessivo, o tratamento combinado de certos psicofármacos com técnicas psicoterapêuticas de cariz cognitivo-comportamental, por exemplo, são alguns dos assuntos tratados. Se bem que neste livro se dê uma mensagem de esperança, dada a ocorrência de avanços recentes consideráveis na compreensão e nas formas de tratamento desta doença, reconhece-se que existe ainda um caminho aberto à investigação científica.

Capítulos de livros publicados Published book chapters

1.	Azevedo, M.H.; Valente, J.; Soares, M.J.; Pereira, A.T.; Macedo, A.. 2012. Aguarda Publicação - Esquizofrenia.  In Neurociências, ed. Catarina Isabel Neno Resende de Olivera (?), 10 - 10. ISBN: 0000. Coimbra, Portugal: Lidel.

2.	Soares, M.J.; Macedo, A.; Azevedo, M.H.. 2012. Aguarda Publicação - Sleep Disturbances and Eating Behaviour in Undergraduate Students..  In Handbook of Nutrition, Diet and Sleep, ed. Preedy, V.R.; Patel, V.B.; Leeds, L., 10 - 10. ISBN: 0000. Londres, Reino Unido: Wageningen Academic Publishers.

3.	Macedo, A.; Azevedo, M.H.. 2009. Relação Médico Doente.  In Manual de Ginecologia, ed. Macedo A. & Azevedo M.H, In Carlos Freire de Oliveira (Coord.), 59 - 79. ISBN: 978-972-733-254-0. Coimbra: Permanyer Portugal. Embora com algumas décadas, a citação introdutória continua com plena actualidade e grande relevância para dar o mote a um capítulo sobre a relação médico-doente (MD). A verdade é que enquanto existirem doentes e médicos e estes não forem substituídos por algum equivalente robótico, a relação MD constitui-se como a matriz e o sustentáculo de toda a prática médica. Apesar de constituir uma evidência, não é demais salientar que o médico não consubstancia um simples “fazedor” de diagnósticos ou dispensador de prescrições. Se assim fosse, poderia até, porventura, ser substituído (se calhar com mais vantagens de economia e fiabilidade) pelo tal robot. É muito mais do que isso, o que fica mais claro quando se evidenciam algumas causas de mal-estar na relação MD, sendo uma das principais a dissonância entre as expectativas do doente e do médico, bem ilustrada pelas palavras de Glick2: There is a major dissonance between the patient’s and the physician’s perception. Patients need caring as much as curing. They insist in both. But modern physicians, enthralled with their newly discovered ability to cure, have learned to seek their gratification in this capacity, often forgetting the caring mode and sometimes leaving patients frustrated and angry even when cured. Como é que um doente curado pode ficar “frustrado” ou mesmo “zangado”? Como iremos mostrar, a compreensão deste aparente paradoxo passa, primeiro, por entendermos a evolução conceptual dos modelos médicos e sua contextualização sociológica, com especial ênfase nos modelos biomédico e biopsicossocial. Após este intróito, focamos a atenção no âmbito da relação MD propriamente dita, onde salientamos a importância central das competências de comunicação requeridas para a satisfação das múltiplas necessidades dos doentes, tal como sintetizadas por Ong et al.3: the need to know and understand (cure) and the need to feel known and understood (care). Depois, e tendo em conta o contexto em que este capítulo se insere (...).

4.	Macedo, A.. 2008. Genética da Doença Bipolar.  In Doença Bipolar: Da Etiologia e Clínica ás Questões Sociais, ed. Adriano Vaz Serra e Maria Luisa Figueira, 19 - 66. ISBN: 978-972-99642-2-0. Lisboa: Laboratórios Pfizer.

5.	Macedo, A.. 2003. Genética das Doenças Afectivas.  In Medicina, Temas Actuais: Depressão, ed. Prof. Doutor Adriano Vaz Serra, 49 - 70. . Castanheira do Ribatejo: Laboratórios Atral, Lda..

Artigos em revistas com arbitragem científica Papers in periodics with scientific refereeing

1.	Bento, C.; Pereira, A.T.; Saraiva, J.M.; Marques, M.; Soares, M.J.; Bos, S.C.; Valente, J.; Azevedo, M.H.; Macedo, A.. 2012. "Confirmar Paginação - Children’s Eating Attitudes Test: Psychometric Characteristics in a Portuguese Adolescent Sample", Eating Behaviours, 0: 0 - 0. Introduction: The Children Eating Attitudes Test (ChEAT; Maloney et al. 1988) is a well-established 26-item scale designed to measure a wide range of problematic eating attitudes and behaviours among children and adolescents. Objective: To analyse ChEAT reliability and validity in a Portuguese adolescent girls sample. Method: 565 high-school girls (mean age 15.76±1.571; mean BMI 20.42 ±2.745) answered the Portuguese versions of ChEAT and of the Contour Drawing Figure Rating Scale (CDFRS; Thompson & Gray, 1995). To study the temporal stability 124 girls answered the ChEAT again after approximately six weeks. Results: Cronbach\'s alpha was of .76. The test-retest Pearson correlation was of 0.61. A four factors structure (explained variance=44.06%) was selected: Factor (F) 1 Fear of Getting Fat, F2 Restrictive and Purging Behaviours, F3 Food Preoccupation, F4 Social Pressure to Eat. The body satisfaction as assessed through CDFRS was negatively correlated with the total ChEAT (-.35), F1 (-.47) and F2 (-.23) (all p>.001); and positively correlated with F4 (.26, p< .001). Significant mean differences (all p< .01) were found between the three CDFRS groups (Group -1 Want to be thinner; Group 0 Satisfied; Group 1 Want to be fatter) in all eating behaviour dimension scores, except for F3; total ChEAT, F1 and F2 mean scores between groups significantly decreased through the body satisfaction groups -1, 0 and 1 and significantly increased for F4. Conclusions The Portuguese ChEAT psychometric characteristics are good. Factorial structure is in accordance with the original. It could be very useful to clinical and epidemiological purposes.

2.	Santos, N.C.; Costa, P.; Ruano, D.; Macedo, A.; Soares, M.J.; Valente, J.; Pereira, A.T.; Azevedo, M.H.; Palha, J.A.. 2012. "Revisiting Thyroid Hormones in Schizophrenia", Journal of Thyroid Research 2012, 1: 1 - 15. Thyroid hormones are crucial during development and in the adult brain. Of interest, fluctuations in the levels of thyroid hormones at various times during development and throughout life can impact on psychiatric disease manifestation and response to treatment. Here we review research on thyroid function assessment in schizophrenia, relating interrelations between the pituitary-thyroid axis and major neurosignaling systems involved in schizophrenia’s pathophysiology. These include the serotonergic, dopaminergic, glutamatergic, and GABAergic networks, as well as myelination and inflammatory processes. The available evidence supports that thyroid hormones deregulation is a common feature in schizophrenia and that the implications of thyroid hormones homeostasis in the fine-tuning of crucial brain networks warrants further research.

3.	Macedo, A.; Pereira, A.T.; Marques, M.; Azevedo, M.H.. 2012. "Confirmar Paginação - To be or not to be perfect? Perfectionism, cognition and psychological distress", Clinical Psychology Review 0, 0: 0 - 0.

4.	Fanous, A.H.; Middleton, F.A.; Gentile, K.L.; Amdur, R.L.; Maher, B.S.; Zhao, Z.; Sun, J.; Medeiros, H.M.; Carvalho, C.; Ferreira, S.R.; Macedo, A.; Knowles, J.A.; Azevedo, M.H.; Pato, M.T.; Pato, C.N.. 2012. "Confirmar Paginação - Genetic overlap of schizophrenia and bipolar disorder in a high-density linkage survey in the Portuguese Island population", American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 159, 1: 1 - 9. Recent family and genome-wide association studies strongly suggest shared genetic risk factors for schizophrenia (SZ) and bipolar disorder (BP). However, linkage studies have not been used to test for statistically significant genome-wide overlap between them. Forty-seven Portuguese families with sibpairs concordant for SZ, BP, or psychosis (PSY, which includes either SZ or psychotic BP) were genotyped for over 57,000 markers using the Affymetrix 50K Xba SNP array. NPL and Kong and Cox LOD scores were calculated in Merlin for all three phenotypes. Empirical significance was determined using 1,000 gene-dropping simulations. Significance of genome-wide genetic overlap between SZ and BP was determined by the number of simulated BP scans having the same number of loci jointly linked with the real SZ scan, and vice versa. For all three phenotypes, a number of regions previously linked in this sample remained so. For BP, chromosome 1p36 achieved significance (11.54-15.71¿MB, LOD¿=¿3.51), whereas it was not even suggestively linked at lower marker densities, as did chromosome 11q14.1 (89.32-90.15¿MB, NPL¿=¿4.15). Four chromosomes had loci at which both SZ and BP had NPL¿=¿1.98, which was more than would be expected by chance (empirical P¿=¿0.01 using simulated SZ scans; 0.07 using simulated BP scans), although they did not necessarily meet criteria for suggestive linkage individually. These results suggest that high-density marker maps may provide greater power and precision in linkage studies than lower density maps. They also further support the hypothesis that SZ and BP share at least some risk alleles.

5.	Soares, M.J.; Macedo, A.; Bos, S.C.; Maia, B.; Marques, M.; Pereira, A.T.; Gomes, A.A.; Valente, J.; Nogueira, V.; Azevedo, M.H.. 2011. "Sleep Disturbances, Body Mass Index and Eating Behaviour in Undergraduate Students", Journal of Sleep Research 20, 3: 479 - 486. Summary This study investigates the association between sleep disturbances, body mass index (BMI) and eating behaviour in a sample of undergraduate students. The sample comprises 870 medicine and dentistry students from Coimbra University (62.5% females), aged between 17 and 25 years. The Eating Attitudes Test-40 was used to measure eating behaviour, and two questions were applied addressing difficulties of initiating sleep (DIS) and difficulties of maintaining sleep (DMS). A sleep disturbance index (SDI) was calculated from the sum of DIS and DMS scores. Body mass index (BMI) was determined from self-reported weight and height. The correlation analyses generally indicated that global eating disturbance, bulimic behaviour dimension and social pressure to eat were associated particularly with sleep difficulties. An association between diet concerns and sleep difficulties was less consistent. Regression analyses showed that bulimic behaviour (BB) and social pressure to eat (SPE) dimensions were associated significantly with sleep difficulties (DIS, DMS, SDI) in the total sample (BB: from P < 0.01 to P < 0.001; SPE: P < 0.05) and in males (BB: from P < 0.05 to P < 0.001; SPE: P < 0.05) and with insomnia symptoms (P < 0.01). In females, bulimic behaviour was the only factor associated significantly with sleep difficulties (SDI, DIS; P < 0.01) and with insomnia symptoms (P < 0.05). Although BMI was correlated negatively with sleep difficulties (P < 0.05), regression analyses indicated that it was not associated significantly with them. Our findings support an association between eating behaviour and sleep disturbances in both genders, which may have treatment implications.

6.	Marques, M.; Bos, S.C.; Soares, M.J.; Maia, B.; Pereira, A.T.; Valente, J.; Gomes, A.A.; Macedo, A.; Azevedo, M.H.. 2011. "Is Insomnia in Late Pregnancy a RiskFactor for Postpartum Depression/Depressive Symptomatology?", Psychiatry Research 186, 2-3: 272 - 280. Abstract The aim of the present work was to investigate if insomnia in late pregnancy is a risk factor for postpartum depressive symptomatology/postpartum depression (PPD). 581 women in their last trimester of pregnancy answered questions/questionnaires about lifetime history of insomnia, current sleep perception, current mood and depressive symptomatology. They were interviewed with the Portuguese version of the Diagnostic Interview for Genetic Studies. After delivery 382 (65.7%) mothers participated again in the study. Insomnia in pregnancy was not a risk factor for PPD (DSM-IV or ICD-10) but was a significant predictor of postpartum depressive symptomatology. Negative Affect (NA) was a significant predictor of postpartum depressive symptomatology. Women with higher NA were 4.6 (CI95% = 1.69–12.74) and 5.3 times (CI95% = 2.26–12.58) more likely of experiencing PPD (DSM-IV/ICD-10, respectively) than women with lower NA. Lifetime Depression was a significant predictor of postpartum depressive symptomatology and ICD-10/PPD (OR = 2.6; CI95% = 1.16–4.38). Positive Affect (PA) showed to be a protective factor for postpartum depressive symptomatology and DSM-IV/PPD (OR = 1.5; CI95% = 1.20–2.33). Controlling NA, PA and Lifetime Depression, insomnia lost its predictive role, suggesting these variables might work as mediators. Associations between insomnia, NA, PA and Lifetime Depression should be assessed in pregnancy. This might help to preventively target NA, enhance PA and reduce the likelihood of experiencing postpartum depressive symptomatology.

7.	Macedo, A.; Marques, M.; Bos, S.; Maia, B.R.; Pereira, T.; Soares, M.J.; Valente, J.; Gomes, A.A.; Nogueira, V.; Azevedo, M.H.. 2011. "Mother's Personality and Infant Temperament", Infant Behavior and Development 34, 4: 552 - 568. We examined if perfectionism and the perception of being an anxious person were associated with more negative infant temperament ratings by the mothers. 386 women (mean age = 30.08; standard deviation = 4.21) in their last trimester of pregnancy completed the Multidimensional Perfectionism Scale (MPS), the Beck Depression Inventory-II (BDI-II) and an item about their perception of being or not an anxious person. The Portuguese version of the Diagnostic Interview for Genetic Studies and the Operational Criteria Checklist for Psychotic Illness were used to generate diagnoses according to DSM-IV and ICD-10 criteria. After delivery, women completed eight items of the Dif¿cult Infant Temperament Questionnaire (developed by our team) and ¿lled in, again, the BDI-II and were interviewed with the DIGS. Women with depression (DSM-IV/ICD-10) and probable cases of depression using different cut-offs adjusted to Portuguese prevalence (BDI-II), in pregnancy and postpartum, were excluded. The Dif¿cult Infant Temperament Questionnaire showed to have factorial validity and internal consistency. There was a statistically signi¿cant negative correlation between perfectionism total scale score and item 6 from the temperament scale (“is your baby irritable or fussy?”). Considering MPS 3-factor solution found for pregnancy there was also a statistically signi¿cant negative correlation between SOP and the same item. Women with low SOP differed from those with medium and high SOP in the total temperament score. Moreover, the low SOP group differed from the medium group on items three and four scores. There were no signi¿cant associations with SPP, which is the dimension more closely associated with negative outcomes. There was an association between anxiety trait status (having it or not) and scoring low, medium or high in the infant temperament scale. The proportion of anxious vs. non-anxious women presenting a high score on the infant temperament scale was higher (24.2% vs. 12.9%)...

8.	Maia, B.; Pereira, A.T.; Marques, M.; Soares, M.J.; Bos, S.C.; Valente, J.; Gomes, A.A.; Nogueira, V.; Azevedo, M.H.; Macedo, A.. 2011. "The Role of Perfectionism in Perinatal Depression (ICD-10, DSM-IV and BDI-II, PDSS)", European Psychiatry 26, 1: 1679 - 1679. Aims The role of perfectionism as a correlate of perinatal depressive symptomatology, and as a predictor of postpartum depressive disorder was examined. Methods 386 women in their third trimester of pregnancy (mean age = 30.08 years; SD = 4.205; range = 19–44) completed the Portuguese versions of Multidimensional Perfectionism Scale, Beck Depression Inventory-II/BDI-II, Postpartum Depression Screening Scale/PDSS and three additional questions evaluating anxiety trait, life stress perception and social support. Diagnoses of depression (ICD-10/DSM-IV) were obtained using the Portuguese version of the Diagnostic Interview for Genetic Studies/OPCRIT system. Women who were clinically depressed in pregnancy (ICD-10/DSM-IV) were excluded from the analysis. Results Self-Oriented Perfectionism/SOP and Socially Prescribed Perfectionism/SPP subcomponents were significant correlates of depressive symptomatology (BDI-II/PDSS) in pregnancy. SPP-Others High Standards/OHS was a significant predictor of postpartum depressive symptomatology (BDI-II/PDSS), and SPP-Conditional Acceptance/CA was a predictor of postpartum depressive symptomatology (PDSS). None of the perfectionism subscales predicted postpartum depressive disorder (ICD-10/DSM-IV). Conclusions SOP and SPP have shown to be relevant correlates of depressive symptomatology in pregnancy. In the present study, SPP-OHS and SPP-CA were also significant correlates of perinatal depressive symptomatology, as well as important risk factors for depressive symptomatology in postpartum. Perfectionism subscales were not significant predictors of postpartum depressive disorder (ICD-10/DSM-IV). While SPP maladaptive influence was supported, SOP was shown to be more heterogeneous in its consequences. These findings may have important implications both for clinical practice and for research.

9.	Bento, C.; Saraiva, J.M.; Pereira, A.T.; Azevedo, M.H.; Macedo, A.. 2011. "Atitudes e Comportamentos Alimentares em uma População Adolescente Portuguesa", Pediatria 33, 1: 21 - 28. Introdução: Os transtornos do comportamento alimentar (TCA) têm aumentado nas últimas décadas. Um dos principais motivos para esse aumento é a pressão sociocultural exercida sobre os adolescentes, que consideram a magreza como um sinal de perfeição e beleza. Devido a essa pressão, muitos jovens adquirem comportamentos alimentares inadequados, e um pequeno número de indivíduos desenvolve TCA. Objetivos: Identificar as atitudes e comportamentos alimentares em uma população de adolescentes, de duas localidades portuguesas (Coimbra - meio urbano e Cantanhede - meio rural), e verificar se existiam diferenças quanto à localização geográfica de residência dos jovens, ao sexo, à idade e ao índice de massa corporal (IMC). Métodos: Estudo epidemiológico, transversal, descritivo e de correlação. O instrumento utilizado foi a versão Portuguesa do Teste de Atitudes Alimentares-25 (TAA-25). Resultados: Obtivemos 997 inquéritos válidos. As idades situaram-se entre os 14 e os 20 anos (média = 16,38; desvio padrão (DP) = 1,19). Um total de 86,6% tinham IMC dentro dos valores normais para a idade. Encontramos atitudes e comportamentos alimentares mais inadequados no sexo feminino, na cidade maior, mas não no grupo de jovens com o IMC mais elevado. Conclusões: A prevalência de atitudes e comportamentos alimentares disfuncionais foi baixa (4%). Foram mais frequentes no sexo feminino e nos que vivem em ambiente urbano, mas não nos adolescentes com IMC mais elevado. Consideramos interessante este último resultado, que contrasta com a restante literatura quanto ao fato de que os comportamentos alimentares disfuncionais são mais frequentes nos adolescentes com IMC mais elevado.(AU).

10.	Bridges, M.; Heron, E.A.; O’Dushlaine, C.T.; Segurado, R.; Morris, D.W.; Corvin, A.; Gill, M.; Pinto, C.; Kliebenstein, D.J.; Kenny, E.; Quinn, E.M.; O’Donovan, M.C.; Kirov, G.K.; Craddock, N.J.; Holmans, P.A.; Williams, N.M.; Georgieva, L.; Nikolov, I.; Norton, N.; Williams, H.; Toncheva, D.; Milanova, V.; Owen, M.J.; Hultman, C.M.; Thelander, E.F.; Sullivan, P.F.; McQuillin, A.; Choudhury, K.; Datta, S.; Pimm, J.; Thirumalai, S.; Puri, V.; Krasucki, R.; Lawrence, J.; Quested, D.; Bass, N.; Gurling, H.M.; Crombie, C.; Fraser, G.; Leh Kwan, S; Walker, N.; St Clair, D; Blackwood, D.H.; Muir, W.J.; McGhee, K.A.; Pickard, B.; Malloy, P.; Maclean, A.W.; Van Beck, M; Wray, N.R.; Visscher, P.M.; Macgregor, S.; Pato, M.T.; Medeiros, H.M.; Middleton, F.A.; Carvalho, C.; Morley, C.P.; Fanous, A.H.; Conti, D.; Knowles, J.A.; Ferreira, C.P.; Macedo, A.; Azevedo, M.H.; Pato, C.N.; Stone, J.L.; Ruderfer, D.M.; Ferreira, M.A.; Purcell, S.M.; Chambert, K.; Kuruvilla, F.; Gabriel, S.B.; Ardlie, K.; Daly, M.J.; Scolnick, E.M.; Sklar, P.. 2011. "Genetic Classification of Populations Using Supervised Learning", PLoS ONE 6, 5: 14802 - 14802. Abstract: There are many instances in genetics in which we wish to determine whether two candidate populations are distinguishable on the basis of their genetic structure. Examples include populations which are geographically separated, case–control studies and quality control (when participants in a study have been genotyped at different laboratories). This latter application is of particular importance in the era of large scale genome wide association studies, when collections of individuals genotyped at different locations are being merged to provide increased power. The traditional method for detecting structure within a population is some form of exploratory technique such as principal components analysis. Such methods, which do not utilise our prior knowledge of the membership of the candidate populations. are termed unsupervised. Supervised methods, on the other hand are able to utilise this prior knowledge when it is available. In this paper we demonstrate that in such cases modern supervised approaches are a more appropriate tool for detecting genetic differences between populations. We apply two such methods, (neural networks and support vector machines) to the classification of three populations (two from Scotland and one from Bulgaria). The sensitivity exhibited by both these methods is considerably higher than that attained by principal components analysis and in fact comfortably exceeds a recently conjectured theoretical limit on the sensitivity of unsupervised methods. In particular, our methods can distinguish between the two Scottish populations, where principal components analysis cannot. We suggest, on the basis of our results that a supervised learning approach should be the method of choice when classifying individuals into pre-defined populations, particularly in quality control for large scale genome wide association studies.

11.	O’Dushlaine, C.T.; Kenny, E.; Heron, E.A.; Donohoe, G.; Gill, M.; Morris, D.W.; Corvin, A.; O’Donovan, M.C.; Kirov, G.K.; Craddock, N.J.; Holmans, P.A.; Williams, N.M.; Georgieva, L.; Nikolov, I.; Norton, N.; Williams, H.; Toncheva, D.; Milanova, V.; Owen, M.J.; Hultman, C.M.; Lichtenstein, P.; Thelander, E.F.; Sullivan, P.F.; McQuillin, A.; Choudhury, K.; Datta, S.; Pimm, J.; Thirumalai, S.; Puri, V.; Krasucki, R.; Lawrence, J.; Quested, D.; Bass, N.; Gurling, H.M.; Crombie, C.; Fraser, G.; Kwan, S.L.; Walker, N.; St Clair, D; Blackwood, D.H.; Muir, W.J.; McGhee, K.A.; Pickard, B.; Malloy, P.; Maclean, A.W.; Van Beck, M; Wray, N.R.; Visscher, P.M.; Macgregor, S.; Pato, M.T.; Medeiros, H.M.; Middleton, F.A.; Carvalho, C.; Morley, C.P.; Fanous, A.H.; Conti, D.; Knowles, J.A.; Ferreira, C.P.; Macedo, A.; Azevedo, M.H.; Pato, C.N.; Stone, J.L.; Ruderfer, D.M.; Ferreira, M.A.; Purcell, S.M.; Chambert, K.; Kuruvilla, F.; Gabriel, S.B.; Ardlie, K.; Daly, M.J.; Scolnick, E.M.; Sklar, P.. 2011. "Molecular pathways involved in neuronal cell adhesion and membrane scaffolding contribute to schizophrenia and bipolar disorder susceptibility", Molecular Psychiatry 16, 3: 286 - 292. Susceptibility to schizophrenia and bipolar disorder may involve a substantial, shared contribution from thousands of common genetic variants, each of small effect. Identifying whether risk variants map to specific molecular pathways is potentially biologically informative. We report a molecular pathway analysis using the single-nucleotide polymorphism (SNP) ratio test, which compares the ratio of nominally significant (P<0.05) to nonsignificant SNPs in a given pathway to identify the ‘enrichment’ for association signals. We applied this approach to the discovery (the International Schizophrenia Consortium (n=6909)) and validation (Genetic Association Information Network (n=2729)) of schizophrenia genome-wide association study (GWAS) data sets. We investigated each of the 212 experimentally validated pathways described in the Kyoto Encyclopaedia of Genes and Genomes in the discovery sample. Nominally significant pathways were tested in the validation sample, and five pathways were found to be significant (P=0.03–0.001); only the cell adhesion molecule (CAM) pathway withstood conservative correction for multiple testing. Interestingly, this pathway was also significantly associated with bipolar disorder (Wellcome Trust Case Control Consortium (n=4847)) (P=0.01). At a gene level, CAM genes associated in all three samples (NRXN1 and CNTNAP2), which were previously implicated in specific language disorder, autism and schizophrenia. The CAM pathway functions in neuronal cell adhesion, which is critical for synaptic formation and normal cell signaling. Similar pathways have also emerged from a pathway analysis of autism, suggesting that mechanisms involved in neuronal cell adhesion may contribute broadly to neurodevelopmental psychiatric phenotypes.

12.	Jia, P.; Wang, L.; Fanous, A.H.; Chen, X.; Kendler, K.S.; Zhao, Z.; O’Dushlaine, C.T.; Kenny, E.; Quinn, E.M.; Gill, M.; Corvin, A.; O’Donovan, M.C.; Kirov, G.K.; Craddock, N.J.; Holmans, P.A.; Williams, N.M.; Georgieva, L.; Nikolov, I.; Norton, N.; Williams, H.; Toncheva, D.; Milanova, V.; Owen, M.J.; Hultman, C.; Lichtenstein, P.; Thelander, E.F.; Sullivan, P.F.; McQuillin, A.; Choudhury, K.; Datta, S.; Pimm, J.; Thirumalai, S.; Puri, V.; Krasucki, R.; Lawrence, J.; Quested, D.; Bass, N.; Gurling, H.M.; Crombie, C.; Fraser, G.; Kwan, S.L.; Walker, N.; St Clair, D; Blackwood, D.H.; Muir, W.J.; McGhee, K.A.; Pickard, B.; Malloy, P.; Maclean, A.W.; Van Beck, M; Wray, N.R.; Visscher, P.M.; Macgregor, S.; Pato, M.T.; Medeiros, H.M.; Middleton, F.A.; Carvalho, C.; Morley, C.P.; Conti, D.; Knowles, J.A.; Ferreira, C.P.; Macedo, A.; Azevedo, M.H.; Pato, C.N.; Stone, J.L.; Ruderfer, D.M.; Ferreira, M.A.; Purcell, S.M.; Chambert, K.; Kuruvilla, F.; Gabriel, S.B.; Ardlie, K.; Daly, M.J.; Scolnick, E.; Sklar, P.; Morris, D.W.. 2011. "A bias-reducing pathway enrichment analysis of genome-wide association data confirmed association of the MHC region with schizophrenia", Journal of Medical Genetics 49, 2: 96 - 103. Background: After the recent successes of genome-wide association studies (GWAS), one key challenge is to identify genetic variants that might have a significant joint effect on complex diseases but have failed to be identified individually due to weak to moderate marginal effect. One popular and effective approach is gene set based analysis, which investigates the joint effect of multiple functionally related genes (eg, pathways). However, a typical gene set analysis method is biased towards long genes, a problem that is especially severe in psychiatric diseases. Methods: A novel approach was proposed, namely generalised additive model (GAM) for GWAS (gamGWAS), for gene set enrichment analysis of GWAS data, specifically adjusting the gene length bias or the number of single-nucleotide polymorphisms per gene. GAM is applied to estimate the probability of a gene to be selected as significant given its gene length, followed by weighted resampling and computation of empirical p values for the rank of pathways. We demonstrated gamGWAS in two schizophrenia GWAS datasets from the International Schizophrenia Consortium and the Genetic Association Information Network. Results: The gamGWAS results not only confirmed previous findings, but also highlighted several immune related pathways. Comparison with other methods indicated that gamGWAS could effectively reduce the correlation between pathway p values and its median gene length. Conclusion: gamGWAS can effectively relieve the long gene bias and generate reliable results for GWAS data analysis. It does not require genotype data or permutation of sample labels in the original GWAS data; thus, it is computationally efficient. .

13.	Maia, B.R.; Marques, M.; Bos, S.C.; Pereira, A.T.; Soares, M.J.; Valente, J.; Macedo, A.; Azevedo, M.H.. 2011. "Confirmar Paginação - Epidemiology of Perinatal Depression in Portugal: Categorical and Dimensional Approach", Acta Médica Portuguesa 0, 0: 0 - 0.

14.	Bos, S.C.; Macedo, A.; Marques, M.; Pereira, A.T.; Maia, B.R.; Soares, M.J.; Valente, J.; Gomes, A.A.; Azevedo, M.H.. 2011. "Confirmar Paginação - Can Positive affect be protective of postpartum depression?", Revista Brasileira de Psiquiatria 95, 1: 0 - 0.

15.	Chen, J.; Lee, G.; Fanous, A.H.; Zhao, Z.; Jia, P.; O'Neill, F.A.; Walsh, D.; Kendler, K.S.; Chen, X.; O’Donovan, M.C.; Kirov, G.K.; Craddock, N.J.; Holmans, P.A.; Williams, N.M.; Georgieva, L.; Nikolov, I.; Norton, N.; Williams, H.; Toncheva, D.; Milanova, V.; Owen, M.J.; Hultman, C.M.; Lichtenstein, P.; Thelander, E.F.; Sullivan, P.F.; Morris, D.W.; O’Dushlaine, C.T.; Kenny, E.; Quinn, E.M.; Gill, M.; Corvin, A.; McQuillin, A.; Choudhury, K.; Datta, S.; Pimm, J.; Thirumalai, S.; Puri, V.; Krasucki, R.; Lawrence, J.; Quested, D.; Bass, N.; Gurling, H.M.; Crombie, C.; Fraser, G.; Kwan, S.L.; Walker, N.; St Clair, D; Blackwood, D.H.; Muir, W.J.; McGhee, K.A.; Pickard, B.; Malloy, P.; Maclean, A.W.; Van Beck, M; Wray, N.R.; Macgregor, S.; Visscher, P.M.; Pato, M.T.; Medeiros, H.; Middleton, F.A.; Carvalho, C.; Morley, C.P.; Conti, D.; Knowles, J.A.; Ferreira, C.P.; Macedo, A.; Azevedo, M.H.; Pato, C.N.; Stone, J.L.; Ruderfer, D.M.; Kirby, A.N.; Ferreira, M.A.; Daly, M.J.; Purcell, S.M.; Sklar, P.; Chambert, K.; Kuruvilla, F.; Gabriel, S.B.; Ardlie, K.; Moran, J.L.; Scolnick, E.M.. 2011. "Two non-synonymous markers in PTPN21, identified by genome-wide association study data-mining and replication, are associated with schizophrenia", Schizophrenia Research 131, 1: 43 - 51. We conducted data-mining analyses of genome wide association (GWA) studies of the CATIE and MGS-GAIN datasets, and found 13 markers in the two physically linked genes, PTPN21 and EML5, showing nominally significant association with schizophrenia. Linkage disequilibrium (LD) analysis indicated that all 7 markers from PTPN21 shared high LD (r(2)>0.8), including rs2274736 and rs2401751, the two non-synonymous markers with the most significant association signals (rs2401751, P=1.10 × 10(-3) and rs2274736, P=1.21 × 10(-3)). In a meta-analysis of all 13 replication datasets with a total of 13,940 subjects, we found that the two non-synonymous markers are significantly associated with schizophrenia (rs2274736, OR=0.92, 95% CI: 0.86-0.97, P=5.45 × 10(-3) and rs2401751, OR=0.92, 95% CI: 0.86-0.97, P=5.29 × 10(-3)). One SNP (rs7147796) in EML5 is also significantly associated with the disease (OR=1.08, 95% CI: 1.02-1.14, P=6.43 × 10(-3)). These 3 markers remain significant after Bonferroni correction. Furthermore, haplotype conditioned analyses indicated that the association signals observed between rs2274736/rs2401751 and rs7147796 are statistically independent. Given the results that 2 non-synonymous markers in PTPN21 are associated with schizophrenia, further investigation of this locus is warranted.

16.	Pereira, A.T.; Bos, S.C.; Marques, M.; Maia, B.; Soares, M.J.; Valente, J.; Gomes, A.A.; Macedo, A.; Azevedo, M.H.. 2010. "The Portuguese Version of the Postpartum Depression Screening Scale", Journal of Psychosomatic Obstetrics & Gynecology 31, 2: 90 - 100. The aim of the present study was to analyse whether the Portuguese version of the Postpartum Depression Screening Scale (PDSS) was a valid instrument for screening postpartum depression. For this purpose the following objectives were delineated: (1) to analyse PDSS psychometric properties; (2) to determine PDSS cut-off points and associated conditional probabilities for screening depression according to DSM-IV and ICD-10 criteria; and (3) to compare the performance of PDSS with the Beck Depression Inventory-II (BDI-II) in screening for postpartum depression. Four hundred eighty-six 3-months-postpartum women completed both questionnaires and were interviewed with the Portuguese version of Diagnostic Interview for Genetic Studies (DIGS). The Portuguese version of the operational criteria checklist for psychotic illness (OPCRIT) was used to obtain DSM-IV and ICD-10 diagnoses of depression, our gold standards for caseness. PDSS reliability and validity were very good and equivalent to those reported in other versions, including the original. PDSS was an accurate screening instrument for postpartum depression, showing satisfactory combination of sensitivity and specificity (>80%). Compared to BDI-II it has the advantage of being more specific for the motherhood context. PDSS could be very useful for clinical and epidemiological purposes. .

17.	Azevedo, M.H.; Bos, S.C.; Soares, M.J.; Marques, M.; Pereira, A.T.; Maia, B.; Gomes, A.A.; Macedo, A.. 2010. "Longitudinal Study on Perfectionism and Sleep Disturbance", World Journal of Biological Psychiatry 11, 2_2: 476 - 485. Abstract AIM: To examine if perfectionism predicts self-reported sleep disturbances over time. METHODS: The Hewitt-Flett Perfectionism Scale was used to assess self-oriented, socially-prescribed (SPP) and other-oriented perfectionism. Sleep disturbance was evaluated with two items: difficulty in falling asleep and waking up many times during the night. Out of 870 students who participated at baseline, 592 and 305 completed the same measures 1 year (T1) and 2 years later (T2), respectively. RESULTS: Subjects who reported insomnia at baseline, T1 and T2 (persistent insomnia) had significantly higher scores of baseline SPP (T1 M = 51.5, SD = 15.8; T2 M = 55.0, SD = 19.0) than subjects reporting, in all stages of the study, never/rarely having had sleep problems (T1 M = 41.9, SD = 11.4; T2 M = 42.2, SD = 12.3, P<0.001 in both cases). Regression analyses showed that baseline SPP was the only significant positive predictor of difficulties in falling asleep at T1 and T2 (T1 partial R=0.187; T2 partial R=0.196, P<0.001) and of difficulties maintaining sleep (T1 partial R=0.116; T2 partial R=0.244, P<0.001).

18.	Bento, C.; Pereira, A.T.; Maia, B.; Marques, M.; Soares, M.J.; Bos, S.; Valente, J.; Gomes, A.; Azevedo, M.H.; Macedo, A.. 2010. "Perfectionism and Eating Behaviour in Portuguese Adolescents", European Eating Disorders Review 18, 4: 328 - 337. Objectives The main objective was to investigate the association between perfectionism and eating behaviour in a non-clinical sample of adolescents of both genders. Method 997 middle and high school students completed the Portuguese versions of the child-adolescent perfectionism scale (CAPS) and of the eating attitudes test -25 (EAT- 25). Results In both genders, the perfectionism total score and the sociallyprescribed perfectionism (SPP) score were positive and significantly correlated with the EAT total score and with all EAT dimensions: Drive for Thinness (DT), Bulimic Related Behaviour (BRB), Social Pressure to Eat (SPE). In girls, self-oriented perfectionism (SOP) was also associated with the EAT total score and its dimensions, whereas in boys it was only associated with EAT total score and DT. In both genders SPP was a useful predictor of the EAT-25 total score and of all its dimensions. In which respects SOP, there were some gender differences showing that in boys this dimension should not be considered a predictor of eating behaviours. Conclusion These results confirm that high levels of perfectionism (SOP and SPP) are associated with abnormal eating behaviour in both genders.

19.	Chen, X.; Lee, G.; Maher, B.S.; Fanous, A.H.; Chen, J.; Zhao, Z.; Guo, A.; van den O. E; Sullivan, P.F.; Shi, J.; Levinson, D.F.; Gejman, P.V.; Sanders, A.; Duan, J.; Owen, M.J.; Craddock, N.J.; O’Donovan, M.C.; Blackman, J.; Lewis, D.; Kirov, G.K.; Qin, W.; Schwab, S.; Wildenauer, D.B.; Chowdari, K.; Nimgaonkar, V.; Straub, R.E.; Weinberger, D.R.; O'Neill, F.A.; Walsh, D.; Bronstein, M.; Darvasi, A.; Lencz, T.; Malhotra, A.K.; Rujescu, D.; Giegling, I.; Werge, T.; Hansen, T.; Ingason, A.; Nöethen, M.M.; Rietschel, M.; Cichon, S.; Djurovic, S.; Andreassen, O.A.; Cantor, R.M.; Ophoff, R.; Corvin, A.; Morris, D.W.; Gill, M.; Pato, C.N.; Pato, M.T.; Macedo, A.; Gurling, H.M.; McQuillin, A.; Pimm, J.; Hultman, C.; Lichtenstein, P.; Sklar, P.; Purcell, S.M.; Scolnick, E.; St Clair, D; Blackwood, D.H.; Kendler, K.S.. 2010. "GWA Study Data Mining and Independent Replication Identify Cardiomyopathy-Associated 5 (CMYA5) as a Risk Gene for Schizophrenia", Molecular Psychiatry 16, 11: 1117 - 1129. Abstract We conducted data-mining analyses using the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and molecular genetics of schizophrenia genome-wide association study supported by the genetic association information network (MGS-GAIN) schizophrenia data sets and performed bioinformatic prioritization for all the markers with P-values =0.05 in both data sets. In this process, we found that in the CMYA5 gene, there were two non-synonymous markers, rs3828611 and rs10043986, showing nominal significance in both the CATIE and MGS-GAIN samples. In a combined analysis of both the CATIE and MGS-GAIN samples, rs4704591 was identified as the most significant marker in the gene. Linkage disequilibrium analyses indicated that these markers were in low LD (3¿828¿611-rs10043986, r(2)=0.008; rs10043986-rs4704591, r(2)=0.204). In addition, CMYA5 was reported to be physically interacting with the DTNBP1 gene, a promising candidate for schizophrenia, suggesting that CMYA5 may be involved in the same biological pathway and process. On the basis of this information, we performed replication studies for these three single-nucleotide polymorphisms. The rs3828611 was found to have conflicting results in our Irish samples and was dropped out without further investigation. The other two markers were verified in 23 other independent data sets. In a meta-analysis of all 23 replication samples (family samples, 912 families with 4160 subjects; case-control samples, 11¿380 cases and 15¿021 controls), we found that both markers are significantly associated with schizophrenia (rs10043986, odds ratio (OR)=1.11, 95% confidence interval (CI)=1.04-1.18, P=8.2 × 10(-4) and rs4704591, OR=1.07, 95% CI=1.03-1.11, P=3.0 × 10(-4)). The results were also significant for the 22 Caucasian replication samples (rs10043986, OR=1.11, 95% CI=1.03-1.17, P=0.0026 and rs4704591, OR=1.07, 95% CI=1.02-1.11, P=0.0015). Furthermore, haplotype conditioned analyses indicated that (...).

20.	Raychaudhuri, S.; Korn, J.M.; McCarroll, S.A.; Altshuler, D.; Sklar, P.; Purcell, S.M.; Daly, M.J.; Allison, D.B.; Azevedo, M.H.; Macedo, A.; Stone, J.L.; Bergen, S.; O’Dushlaine, C.T.; Ruderfer, D.M.; Scolnick, E.M.; Chambert, K.; O’Donovan, M.C.; Kirov, G.K.; Craddock, N.J.; Holmans, P.A.; Williams, N.M.; Georgieva, L.; Nikolov, I.; Norton, N.; Williams, H.; Toncheva, D.; Milanova, V.; Owen, M.J.; Hultman, C.; Lichtenstein, P.; Thelander, E.F.; Sullivan, P.F.; Morris, D.W.; Kenny, E.; Waddington, J.L.; Gill, M.; Corvin, A.; McQuillin, A.; Choudhury, K.; Datta, S.; Pimm, J.; Thirumalai, S.; Puri, V.; Krasucki, R.; Lawrence, J.; Quested, D.; Bass, N.; Curtis, D.; Gurling, H.M.; Crombie, C.; Fraser, G.; Kwan, N.; Walker, N.; St Clair, D; Blackwood, D.H.; Muir, W.J.; McGhee, K.A.; Maclean, A.W.; Van Beck, M; Visscher, P.M.; Macgregor, S.; Wray, N.R.; Pato, M.T.; Medeiros, H.M.; Middleton, F.A.; Carvalho, C.; Morley, C.P.; Fanous, A.H.; Conti, D.; Knowles, J.A.; Ferreira, C.P.; Pato, C.N.. 2010. "Accurately Assessing the Risk of Schizophrenia Conferred by Rare Copy-Number Variation Affecting Genes with Brain Function", PLoS Genetics 6, 9: 1001097 - 1001097. Abstract: Investigators have linked rare copy number variation (CNVs) to neuropsychiatric diseases, such as schizophrenia. One hypothesis is that CNV events cause disease by affecting genes with specific brain functions. Under these circumstances, we expect that CNV events in cases should impact brain-function genes more frequently than those events in controls. Previous publications have applied "pathway" analyses to genes within neuropsychiatric case CNVs to show enrichment for brain-functions. While such analyses have been suggestive, they often have not rigorously compared the rates of CNVs impacting genes with brain function in cases to controls, and therefore do not address important confounders such as the large size of brain genes and overall differences in rates and sizes of CNVs. To demonstrate the potential impact of confounders, we genotyped rare CNV events in 2,415 unaffected controls with Affymetrix 6.0; we then applied standard pathway analyses using four sets of brain-function genes and observed an apparently highly significant enrichment for each set. The enrichment is simply driven by the large size of brain-function genes. Instead, we propose a case-control statistical test, cnv-enrichment-test, to compare the rate of CNVs impacting specific gene sets in cases versus controls. With simulations, we demonstrate that cnv-enrichment-test is robust to case-control differences in CNV size, CNV rate, and systematic differences in gene size. Finally, we apply cnv-enrichment-test to rare CNV events published by the International Schizophrenia Consortium (ISC). This approach reveals nominal evidence of case-association in neuronal-activity and the learning gene sets, but not the other two examined gene sets. The neuronal-activity genes have been associated in a separate set of schizophrenia cases and controls; however, testing in independent samples is necessary to definitively confirm this association. Our method is implemented in the PLINK software (...).

21.	Pereira, A.T.; Bos, S.C.; Marques, M.; Maia, Berta R; Soares, M.J.; Valente, J.; Gomes, A.A.; Macedo, António; Azevedo, M.H.. 2010. "The Postpartum Depression Screening Scale: Is it Valid to Screen for Antenatal Depression?", Archives of Women's Mental Health 14, 3: 227 - 238. Abstract The purpose of the study was to analyse for the first time the validity of a slightly modified version of the Portuguese Postpartum Depression Screening Scale (PDSS), to be used as a screening instrument for antenatal depression. Specifically, the aims were to analyse its psychometric properties, to determine PDSS cutoff points and associated conditional probabilities to screen for depression according to DSM-IV and ICD-10 criteria and to compare its screening performance with that of the Beck Depression Inventory-II (BDI-II). Five hundred and three pregnant women in the third trimester of pregnancy completed both questionnaires and were interviewed face-to-face with the Portuguese version of the Diagnostic Interview for Genetic Studies. The Portuguese version of the Operational Criteria Checklist for Psychotic Illness was used to obtain DSM-IV and ICD-10 diagnoses of depression, our gold standards for caseness. PDSS reliability and validity were very good and comparable to those obtained in the postpartum validation studies developed in Portugal and in other countries, showing satisfactory sensitivity and specificity combinations (¿80%). Compared with BDI-II, it has the advantage of being more specific for the motherhood context. Although developed for postpartum depression, PDSS is accurate to screen for antenatal depression, and it could be very useful for clinical and epidemiologic purposes.

22.	Maia, B.R.; Soares, M.J.; Gomes, A.A.; Marques, M.; Pereira, A.T.; Cabral, A.S.; Valente, J.; Bos, S.C.; Pato, M.T.; Pocinho, F.; Azevedo, M.H.; Macedo, A.. 2009. "Perfectionism in Obsessive-Compulsive and Eating Disorders", Revista Brasileira de Psiquiatria 31, 4: 322 - 327. ABSTRACT OBJECTIVE: The main aims of this article are twofold. First, to assess perfectionism dimensions in obsessive-compulsive disorder and eating disorders in comparison with psychiatric control (depression/anxiety) and non-clinical control groups. Second, to examine if perfectionism is specifically related to these different clinical conditions. METHOD: Thirty-nine outpatients with obsessive-compulsive disorder, 24 outpatients with eating disorders, 65 outpatients with a diagnosis of depression and/or anxiety, and 70 non-clinical participants completed the Portuguese version of the Multidimensional Perfectionism Scale. RESULTS: Compared to non-clinical subjects, individuals of all clinical samples had significantly higher scores on Multidimensional Perfectionism Scale total score, Self-Oriented and Socially-Prescribed Perfectionism. There were no significantly differences in Self-Oriented Perfectionism and Multidimensional Perfectionism Scale total score in all the three clinical samples. Subjects from the eating disorders sample had significantly higher scores of Socially-Prescribed Perfectionism in comparison to obsessive-compulsive disorder and psychiatric control samples. CONCLUSION: Perfectionism showed to be related with this broad range of psychopathologies. However, the differences between eating disorders versus obsessive-compulsive disorder and psychiatric control on Socially-Prescribed Perfectionism warrant further investigation in order to clarify the specificity of this perfectionism dimension in eating disorders.

23.	Pereira, A.T.; Maia, B.R.; Marques, M.; Bos, S.C.; Soares, M.J.; Macedo, A.; Azevedo, M.H.. 2009. "Reply to the Comment on "Factor Structure of the Rutter Teacher Questionnaire in Portuguese children"", Revista Brasileira de Psiquiatria 31, 3: 284 - 285. Dear Editor, We greatly appreciate the interest expressed by Érico Moura and Simone Hauck in our paper, which is entitled “Factor structure of the Rutter Teacher Questionnaire in Portuguese children”. The aim of this study was to explore the Rutter Scale B2 factorial structure in a large sample of Portuguese children. As previously acknowledged by commentators, it is crucial that upon its adaptation to another culture, the factorial structure be reviewed. Indeed, this is one of the recommended methods to investigate its construct validity.1 This being the case, it is not entirely surprising that, when comparing the Portuguese RB2 factor structure against both the original Rutter subscales2 and other factor structures, (e.g.3,4), some differences can be observed. Although the total percentage of variance seen (38.8%) was not high, the fact that the first factor (hyperactivity/conduct) explained approximately half of the total percentage, and that the double of that explained by the second factor (anxious/depressive, 9.48%) is common and expected.1 Moreover, if it can be argued that the use of a screen test based on the Cattell criteria to extract the number of factors results in a certain level of subjectivity, then the decision made was to first submit it to an inter-rater reliability test. All researchers i.e., 5 psychologists and 4 psychiatrists with clinical experience in child psychiatry among other specialties agreed on a three-factor structure. After analysing the items’ content, all five considered this to be a clinically significant solution. We believe that the comprehensibility of factors is an important aspect in their selection. As pointed out in the discussion, please note that the factorial structure obtained does reflect the hyperkinetic conduct disorder as described in ICD-10,5 which empirically validates both the classification and the factorial structure. (...).

24.	Bos, S.C.; Gomes, A.A.; Clemente, V.; Marques, M.; Pereira, A.T.; Maia, B.; Soares, M.J.; Cabral, A.S.; Macedo, A.; Gozal, D.; Azevedo, M.H.. 2009. "Sleep and Behavioral/Emotional Problems in Children: A Population-Based Study", Sleep Medicine 10, 1: 66 - 74. Abstract BACKGROUND: The potential relationships between sleep-wake behaviors and emotional/disruptive problems in otherwise healthy school-aged children are unclear. METHODS: A parental questionnaire was developed for the epidemiologic survey of children's sleep and wake behavioral patterns. The questions covered a wide range of features including sleep length (school days, weekends), time to fall asleep, night awakenings, bedtime and nighttime sleep-related behaviors, daytime sleepiness, irritability, and tiredness. To assess psychiatric symptomatology, the Rutter Scale B2 was completed by teachers. In addition to the total score, sub-scores of emotional, hyperactivity, and conduct problems were obtained. The representative population sample comprised 779 children (403 girls), with an age range of 6-11 years. RESULTS: Hyperactivity and conduct problems at school in boys were both associated with parental reports of bedtime resistance. Hyperactivity was also associated with longer sleep duration during weekends. Conduct and emotional problems in girls were associated with earlier bedtime during school days. Emotional problems in girls were also associated with longer sleep durations in school days and weekends. CONCLUSION: Bedtime resistance was the only sleep behavior associated with either hyperactivity or conduct problems in children, and longer sleep durations appear to occur more frequently in children with both hyperactive or emotional problems. Information about good sleep hygiene at bedtime may help parents setting sleep limits.

25.	Soares, M.J.; Macedo, A.; Bos, S.C.; Marques, M.; Maia, B.; Pereira, A.T.; Gomes, A.A.; Valente, J.; Pato, M.T.; Azevedo, M.H.. 2009. "Perfectionism and Eating Attitudes in Portuguese Students: A Longitudinal Study", European Eating Disorders Review 17, 5: 390 - 398. Abstract Aim: To investigate the role of perfectionism in the development of disordered eating behaviours. Method: 382 female university students completed the Hewitt & Flett MPS and the EAT-40 at baseline, and 1 year after (T1) and 206 2 years later (T2). Results: Perfectionism at baseline was signi¿cantly associated with long-term abnormal eating attitudes/behaviours. Self-Oriented Perfectionism (SOP) and Socially Prescribed Perfectionism (SPP) were signi¿cant predictors of disordered eating behaviours. Regression analysis revealed that SOP at baseline was predictive of Diet Concerns and overall eating disturbance (EAT total score), at T1 and T2. SPP was a signi¿cant predictor of Social Pressure to Eat at T1 and T2 and of Bulimic Behaviours only at T1. Conclusion: Our ¿ndings contribute to a more clear understanding of the association between perfectionism and eating disorders. SOP and SPP were prospectively associated with abnormal eating attitudes/behaviours and SOP was found to be predictive of diet concerns and overall eating disturbance. Copyright#2009 John Wiley & Sons, Ltd and Eating Disorders Association.

26.	Bos, S.; Pereira, A. T; Marques, M.; Maia, B.R.; Soares, M. J; Valente, J.; Gomes, A.A.; Macedo, A.; Azevedo, M. H. P. 2009. "The BDI-II Factor Structure in Pregnancy and Postpartum: Two or Three Factors?", European Psychiatry 24, 5: 334 - 340. Abstract The purpose of the present study was to investigate the factor structure of the Beck Depression Inventory-II (BDI-II) in pregnancy and postpartum. Women were asked to fill in the BDI-II in their last trimester of pregnancy and at 3 months after delivery. A total of 331 pregnant women, with a mean age of 29.7 years (SD=4.6), and 354 mothers, aged 30.6 years (SD=4.6 years), answered the BDI-II. The first group was mainly nulliparas (65.6%) and the second group was mostly primiparas (57.4%). Factor analyses with principal components solution and varimax rotation were performed. Based on the scree test of Cattell a 2-factor solution and a 3-factor solution were explored. The 2-factor solution was identical in pregnancy and postpartum. Items loading in the Cognitive-Affective factor and in the Somatic-Anxiety factor were almost the same, though the Cognitive-Affective factor explained more of the BDI-II total variance in pregnancy, whereas in postpartum both factors explained similar total variances. The 3-factor solution of the BDI-II in pregnancy and postpartum slightly diverged. Besides the Cognitive-Affective and the Somatic-Anxiety factors, a third factor, Fatigue, was obtained in pregnancy while Guilt was the third factor identified in postpartum. This study reveals that the BDI-II 3-factor solution might be more appropriate to assess depressive symptoms in pregnancy and postpartum.

27.	de Azevedo, M. H. P; Soares, Maria J; Carvalho Bos, S; Allen Gomes, A; Maia, Berta; Marques, Mariana; Pereira, Ana T; Macedo, António. 2009. "Perfectionism and Sleep Disturbance", World Journal of Biological Psychiatry 10, 3: 225 - 233. The main purpose of the present research was to explore gender-related associations between sleep disturbance and perfectionism dimensions in a large sample of undergraduate students. Perfectionism dimensions have been assessed using the Portuguese version of the Multidimensional Perfectionism Scale (Hewitt and Flett, 1991, J Pers Soc Psychol 60:456; Soares et al., 2003, Rev Port Psicossom 5:46) and sleep disturbance with two items concerning difficulties initiating sleep and difficulties maintaining sleep. A total of 1163 undergraduate students of both genders between 17 and 25 years of age completed the scale. Results from correlational and categorial analyses indicated that socially prescribed perfectionism was the only dimension associated with sleep disturbance in undergraduate students of both genders. Males with the highest levels of socially prescribed perfectionism were approximately twice more likely to report sleep disturbances than those with less socially prescribed perfectionism. Similar results were found within the female sample. Implications for future research and clinical practice are discussed.

28.	Macedo, António; Bos, Sandra C; Marques, Mariana; Maia, Berta; Soares, Maria J; Pereira, Telma; Gomes, Ana A; Valente, José; Azevedo, Maria H. 2009. "Perfectionism Dimensions in Pregnancy—A Study in Portuguese Women", Archives of Women's Mental Health 12, 1: 43 - 52. Abstract Pregnancy is essentially a physiological event, but neuroendocrinal and psychosocial changes are also important components of this experience. In this context, perceived stress may be enhanced by the activation of certain personality traits, like perfectionism, which in turn may be associated with more psychological distress (PD). The aim of this study was to investigate if perfectionism could be associated with more negative emotional outcomes (PD) in the transition to motherhood and to look at which of the perfectionism dimensions these consequences are specifically linked. The sample comprises 421 pregnant women (mean¿=¿29.8, SD¿=¿4.48 years) who completed measures of perfectionism and mood symptoms. A two-factor model with self-oriented perfectionism (SOP) and socially prescribed perfectionism (SPP) dimensions and a three-factor model with SOP, SPP-others’ high standards and SPP-conditional acceptance (CA) factors were explored. Correlations and linear regressions were calculated between perfectionism factors and mood variables. Results showed that higher levels of SPP factors were associated with increased anxiety, depression, anger, fatigue and confusion, with decreased vigour and with more severe depressive symptoms. Our results, in contrast with those from the study of Campbell and DiPaula (2002, In: Flett G, Hewitt P (eds) Perfectionism. Theory, research, and practice. American Psychological Association, Washington, pp 181–198), did not confirm a preferential association between SPP-CA and PD, revealing that both components of SPP were associated with PD.

29.	Marques, M.; Macedo, A.; Soares, M.J.; Maia, B.; Pereira, A.T.; Bos, S.C.; Gomes, A.A.; Valente, J.; Azevedo, M.H.. 2009. "Can We Tallk About “Premedical Syndrome” Among Portuguese Medical Students", Acta Médica Portuguesa 22, 6: 789 - 796. Introdução: Em Portugal, o processo de selecção das Faculdades de Medicina baseia-se exclusivamente nos resultados académicos prévios, exigindo os resultados mais elevados de todos os cursos, não se atribuindo atenção aos traços de personalidade dos alunos. Num contexto altamente competitivo revela-se importante considerar as dimensões do perfeccionismo. O Perfeccionismo Socialmente Prescrito (PSP) tem-se mostrado correlacionado com o Neuroticismo e o Perfeccionismo Auto-Orientado (PAO) revela-se fortemente associado com a Conscienciosidade. Estes domínios de Personalidade têm sido associados (níveis baixos de Neuroticismo e níveis altos de Conscienciosidade) ao sucesso académico e profissional em Medicina. O premedical syndrome descreve os alunos que pretendem entrar nas Faculdades de Medicina como overachieving, excessively competitive, cynical, dehumanized, overspecialized and narrow. O nosso objectivo foi comparar os níveis de PSP e PAO entre alunos dos cursos de Medicina e de Letras, uma vez que podem ser indicadores da presença do premedical syndrome entre os alunos que, em Portugal, ingressam na Faculdade de Medicina. Material e Métodos: A versão portuguesa da Multidimensional Perfectionism Scale foi administrada a 908 alunos dos cursos de Medicina e de Letras da Universidade de Coimbra. A amostra envolveu alunos do primeiro até ao quinto ano dos cursos, mas a maioria dos alunos frequentava o primeiro ano do curso (n = 436). Resultados: Encontraram-se diferenças estatisticamente significativas quanto ao PSP, com os alunos de Medicina a revelarem valores mais baixos (média 48.60±11.02; p = .023) do que os alunos de Letras (média 50.00±9.56). Relativamente ao PAO, não foram encontradas diferenças estatisticamente significativas. Discussão e Conclusão: Os resultados são tranquilizadores, sugerindo não se verificar um impacto negativo do processo de selecção para as Faculdades de Medicina, nos traços de personalidade dos alunos e a provável inexistência do pre.

30.	Purcell, S.M.; O’Dushlaine, C.T.; O’Donovan, M.C.; Sullivan, P.F.; Sklar, P.; O'Donovan, Michael C; Kirov, G.K.; Craddock, N.J.; Holmans, P.A.; Williams, N.M.; Georgieva, L.; Nikolov, I.; Norton, N.; Williams, H.; Toncheva, D.; Milanova, V.; Owen, Michael J; Hultman, C.M.; Lichtenstein, P.; Thelander, E.F.; Morris, D.W.; Kenny, E.; Quinn, E.M.; Gill, M.; Corvin, A.; McQuillin, A.; Choudhury, K.; Datta, S.; Pimm, J.; Thirumalai, S.; Puri, V.; Krasucki, R.; Lawrence, J.; Quested, D.; Bass, N.; Gurling, H.M.; Crombie, C.; Fraser, G.; Leh Kwan, S; Walker, N.; St Clair, D; Blackwood, D.H.; Muir, W.J.; McGhee, K.A.; Pickard, B.; Malloy, P.; Maclean, A.W.; Van Beck, M; Wray, N.R.; Macgregor, S.; Visscher, P.M.; Pato, M.T.; Medeiros, H.; Middleton, F.A.; Carvalho, C.; Morley, C.P.; Fanous, A.H.; Conti, D.; Knowles, J.A.; Ferreira, C.P.; Macedo, A.; Azevedo, M.H.; Pato, C.N.; Kirby, A.N.; Ferreira, M.A.; Stone, J.L.; Chambert, K.; Ruderfer, D.M.; Kuruvilla, F.; Gabriel, S.B.; Ardlie, K.; Moran, J.L.; Daly, M.J.; Scolnick, E.M.. 2009. "Common Polygenic Variation Contributes to Risk of Schizophrenia and Bipolar Disorder", Nature 6, 460: 748 - 752. Abstract Schizophrenia is a severe mental disorder with a lifetime risk of about 1%, characterized by hallucinations, delusions and cognitive deficits, with heritability estimated at up to 80%. We performed a genome-wide association study of 3,322 European individuals with schizophrenia and 3,587 controls. Here we show, using two analytic approaches, the extent to which common genetic variation underlies the risk of schizophrenia. First, we implicate the major histocompatibility complex. Second, we provide molecular genetic evidence for a substantial polygenic component to the risk of schizophrenia involving thousands of common alleles of very small effect. We show that this component also contributes to the risk of bipolar disorder, but not to several non-psychiatric diseases.

31.	Gomes, A.A.; Cabral, A.S.; Marques, M.; Pereira, A.T.; Maia, B.; Soares, M.J.; Valente, J.; Macedo, A.; Clemente, V.; Azevedo, M.H.. 2009. "Teacher Reports of Emotional and Disruptive Behaviours in Portuguese Children", European Psychiatry 24, S1: 791 - 791. The aim of the present study was to determine the frequency of emotional and disruptive behaviours and the rates of hyperactivity, conduct and emotional problems in school-aged children. The Rutter Children’s Behaviour Questionnaire for completion by teachers was used to assess psychiatric symptoms. A total deviance score is derived from the sum of scores for the individual items (n= 26). An emotional sub-score can be obtained from the sum of scores of four items (worried, miserable, fearful, tears on arrival at school), a conduct sub-score obtained from the sum of scores of six items (destructive, fights, disobedient, lies, steals, bullies) and a hyperactivity sub-score obtained from the sum of scores of three items (restless/overactive, poor concentration, fidgety/squirmy). The sample comprised 877 children (446 girls) with an age range between 6 and 11 years. Compared to girls, boys showed a significantly higher frequency of restless/overactive (15.8% vs. 5.8%), fidgety/squirmy (9.3% vs. 3.6%), fights (6.3% vs. 2.2%), disobedient (6.0% vs. 2.7%), bullies (5.3% vs. 2.0%) and irritable (5.1% vs. 1.8%) behaviours. Rates of conduct and hyperactivity behavioural problems were also significantly more frequent in boys than in girls (conduct problems: 17.9% vs. 8.1%; hyperactivity problems: 20.4% vs. 9.6%). The high rates of disruptive behaviours and problems in boys are in accordance with the literature.

32.	Pereira, A.T.; Maia, B.; Bos, S.C.; Soares, M.J.; Marques, M.; Macedo, A.; Azevedo, M.H.. 2008. "The Portuguese Short Form of the Eating Attitudes Test¿?40", European Eating Disorders Review 16, 4: 319 - 325. Abstract: To develop a Portuguese short form, the Eating Attitudes Test-40 (EAT-40) was administered to a community sample of 922 female students and to a clinical sample of 63 females suffering from an eating disorder. With the EAT responses of the community sample a factor analysis was performed and items with factor loadings¿=¿0.30 were selected. Internal consistency was computed for both the instrument and the factors. To study the discriminant capacity the proportion of symptomatic answers and the mean scores were compared between the clinical (N¿=¿63) and control (N¿=¿63) samples. Three factors were extracted: Drive for Thinness (14 items, a¿=¿.839), Bulimic Behaviours (8 items, a¿=¿.670), Social Pressure to Eat (3 items, a¿=¿.758). The short form is composed of 25 items and shows good internal consistency¿=¿0.839. Symptomatic answers for all items (except one) and total mean scores were significantly higher (p¿<¿.001) in the clinical sample than in community sample. Copyright © 2007 John Wiley & Sons, Ltd and Eating Disorders Association.

33.	Pereira, A.T.; Maia, B.; Marques, M.; Bos, S.C.; Soares, M.J.; Gomes, A.A.; Macedo, A.; Azevedo, M.H.. 2008. "Factor Structure of the Rutter Teacher Questionnaire in Portuguese Children", Revista Brasileira de Psiquiatria 30, 4: 322 - 327. ABSTRACT OBJECTIVE: To examine the factor structure of the Rutter Teacher Questionnaire in Portuguese primary school children. METHOD: The Rutter Teacher Questionnaire, a 26-item scale covering a variety of behavioral problems, was completed by teachers of 877 children, aged 6 to 11 years. Data were subjected to factor analysis using the principal components solution with varimax rotation. RESULTS: The factorial analysis in total sample revealed three factors explaining 38.88% of the total variance. The factors contained items representing hyperactivity/conduct (Factor 1), anxious/depressive (Factor 2) and truancy/stealing (Factor 3). The highest correlations between factors scores were for Factor 1 and Factor 3. These Factors scores were higher in boys than girls and correlated with lower social class. All three Factors scores correlated with school performance. The comparison between separate factorial structures for the samples of boys and girls revealed a considerable overlap. CONCLUSIONS: The pattern of the items contained on Factor 1 appears to be related with the category of hyperkinetic conduct disorder used by the International Classification of Diseases-10. Results suggest that the Portuguese language version of the Rutter Teacher Questionnaire possesses good psychometric properties and may be considered a useful instrument for measuring children's behavior problems. Descriptors: Portugal; Questionnaires; Factor analysis, statistical; Child behavior; Evaluation studies.

34.	Ruano, D.; Aulchenko, Y.S.; Macedo, A.; Soares, M.J.; Valente, José; Azevedo, M.H.; Hutz, M.H.; Gama, C.G.; Lobato, M.I.; Belmonte-de-Abreu, P.; Goodman, A.B.; Pato, C.N.; Heutink, P.; Palha, J.A.. 2008. "Association of the Gene Encoding Neurogranin with Schizophrenia in Males", Journal of Psychiatric Research 42, 2: 125 - 133. Abstract The neurogranin (NRGN) gene produces a postsynaptic brain-specific protein that regulates calmodulin-Ca2+ availability in neurons. Acting downstream of the NMDA receptor and upstream of calcineurin and other proteins implicated in schizophrenia, NRGN is a good candidate for association studies in schizophrenia. NRGN expression is regulated during development and is modulated by thyroid hormones and retinoids, molecules essential for the proper development of the central nervous system. Given the genetic complexity of schizophrenia and the potential genetic heterogeneity in different populations, we studied a possible association of NRGN with schizophrenia in 73 Azorean proband-parent triads and in two independent case-control samples from the Portuguese-mainland (244 schizophrenic and 210 controls) and Brazil (69 schizophrenic and 85 mentally healthy individuals). Genotype distribution showed association of the rs7113041 SNP with schizophrenia in males of Portuguese origin, which was confirmed by the analysis of the proband-parent triads. This evidence, implicating NRGN in schizophrenia, introduces another player into the glutamatergic hypothesis of schizophrenia.

35.	Purcell, S.M.; Sullivan, P.F.; Sklar, P.; O’Donovan, M.C.; Kirov, G.K.; Craddock, N.J.; Holmans, P.A.; Williams, N.M.; Georgieva, L.; Nikolov, I.; Norton, N.; Williams, H.; Toncheva, D.; Milanova, V.; Owen, Michael J; Hultman, C.M.; Lichtenstein, P.; Thelander, E.F.; Morris, D.W.; O’Dushlaine, C.T.; Kenny, E.; Waddington, J.L.; Gill, M.; Corvin, A.; McQuillin, A.; Choudhury, K.; Datta, S.; Pimm, J.; Thirumalai, S.; Puri, V.; Krasucki, R.; Lawrence, J.; Quested, D.; Bass, N.; Curtis, D.; Gurling, H.M.; Crombie, C.; Fraser, G.; Leh Kwan, S; Walker, N.; St Clair, D; Blackwood, D.H.; Muir, W.J.; McGhee, K.A.; Pickard, B.; Malloy, P.; Maclean, A.W.; Van Beck, M; Visscher, P.M.; Macgregor, S.; Pato, M.T.; Medeiros, H.; Middleton, F.A.; Carvalho, C.; Morley, C.P.; Fanous, A.; Conti, D.; Knowles, J.A.; Ferreira, C.P.; Macedo, A.; Azevedo, M.H.; Pato, C.N.; Stone, Jennifer L; Chambert, K.; Ruderfer, D.M.; Korn, J.; McCarroll, S.A.; Gates, C.; Gabriel, S.B.; Mahon, S.; Ardlie, K.; Daly, M.J.; Scolnick, E.M.. 2008. "Rare Chromosomal Deletions and Duplications Increase Risk of Schizophrenia", Nature 455, 7210: 237 - 241. Abstract Schizophrenia is a severe mental disorder marked by hallucinations, delusions, cognitive deficits and apathy, with a heritability estimated at 73-90% (ref. 1). Inheritance patterns are complex, and the number and type of genetic variants involved are not understood. Copy number variants (CNVs) have been identified in individual patients with schizophrenia and also in neurodevelopmental disorders, but large-scale genome-wide surveys have not been performed. Here we report a genome-wide survey of rare CNVs in 3,391 patients with schizophrenia and 3,181 ancestrally matched controls, using high-density microarrays. For CNVs that were observed in less than 1% of the sample and were more than 100 kilobases in length, the total burden is increased 1.15-fold in patients with schizophrenia in comparison with controls. This effect was more pronounced for rarer, single-occurrence CNVs and for those that involved genes as opposed to those that did not. As expected, deletions were found within the region critical for velo-cardio-facial syndrome, which includes psychotic symptoms in 30% of patients. Associations with schizophrenia were also found for large deletions on chromosome 15q13.3 and 1q21.1. These associations have not previously been reported, and they remained significant after genome-wide correction. Our results provide strong support for a model of schizophrenia pathogenesis that includes the effects of multiple rare structural variants, both genome-wide and at specific loci.

36.	Macedo, A.; Soares, M.J.; Azevedo, M.H.; Gomes, A.A.; Pereira, A.T.; Maia, B.R.; Pato, M.T.. 2007. "Perfectionism and Eating Attitudes in Portuguese University Students", European Eating Disorders Review 15, 4: 296 - 304. Objectives: The main objective was to explore which are the dimensions of perfectionism that are linked to disordered eating behaviour (EB) in a large non-clinical sample of both genders. Method: One thousand one hundred and sixty-three undergraduate students of the University of Coimbra completed the Portuguese versions of the multidimensional perfectionism scale (MPS) and the eating attitudes test (EAT-40). Results: In both genders, the MPS total score was associated with the EAT total score and all EAT dimensions (except for socially prescribed perfectionism in females). Self-oriented perfectionism (SOP) and socially prescribed perfectionism (SPP) were associated with EAT total score, diet concerns (DC) and bulimic behaviour (BB) in females while in males the social prescribed perfectionism (SPP) was the useful predictor of EAT total score, BB and social pressure to eat (SPE). Conclusion: These results confirm that in general high levels of perfectionism are associated with abnormal EB. This was the case for both genders for SPP but for SOP for females only. The association for other oriented perfectionism (OOP) was greater for males than for females.

37.	Ruano, D.; Macedo, A.; Soares, M. J; Valente, J.; Azevedo, M.H.; Hutz, M.H.; Gama, C.G.; Lobato, M.I.; Belmonte-de-Abreu, P.; Goodman, A.B.; Pato, C.N.; Saraiva, M.J.; Heutink, P.; Palha, J.A.. 2007. "Transthyretin: No Association Between Serum Levels or Gene Variants and Schizophrenia", Journal of Psychiatric Research 41, 8: 667 - 672. Abstract It has been proposed that schizophrenia results from an environmental insult in genetically predisposed individuals. Environmental factors capable of modulating transcriptional activity and their carriers could link the genetic and environmental components of schizophrenia. Among these is transthyretin (TTR), a major carrier of thyroid hormones and retinol-binding protein (RBP). Retinoids and thyroid hormones regulate the expression of several genes, both during development and in the adult brain. Decreased TTR levels have been reported in the cerebrospinal fluid of patients with depression and Alzheimer’s disease, and the absence of TTR influences behavior in mice. DNA variants capable of altering TTR ability to carry its ligands, either due to reduced transcription of the gene or to structural modifications of the protein, may influence development of the central nervous system and behavior. In the present study we searched for variants in the regulatory and coding regions of the TTR gene, and measured circulating levels of TTR and RBP. We found a novel single nucleotide polymorphism (SNP), ss46566417, 18 bp upstream of exon 4. Neither this SNP nor the previously described rs1800458 were found associated with schizophrenia. In addition, serum TTR and RBP levels did not differ between mentally healthy and schizophrenic individuals. In conclusion, our data does not support an involvement of the TTR gene in the pathophysiology of schizophrenia.

38.	Ruano, D.; Macedo, A.; Soares, M.J.; Valente, J.; Azevedo, M.H.; Pato, C.N.; Hutz, M.H.; Gama, C.G.; Lobato, M.I.; Belmonte-de-Abreu, P.; Heutink, P.; Palha, J.A.. 2007. "Family-Based and Case-control Studies Reveal no Association Oflipocalin-type Prostaglandin D2 Synthase with Schizophrenia", American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 144, 5: 642 - 646. Abstract Several observations point to the involvement of disturbed lipid biology in schizophrenia. Reduced response to niacin flushing test, which involves vasodilatation induced by prostaglandin D2 (PGD2), is among the evidences, together with decreased CSF levels of lipocalin-type prostaglandin D2 synthase (PTGDS), the enzyme responsible for the synthesis of PGD2 in the brain. Since PTGDS is also a carrier for lipophilic molecules such as retinoids and thyroid hormones, altered PTGDS levels might influence both PGD2-mediated signaling, and vitamin A and thyroid hormone availability. To test whether genetic variants of PTGDS are involved in the etiology of schizophrenia, we searched for variants in the coding and regulatory regions of the gene. We identified four previously described polymorphisms. Using two case-control samples from Portugal and Brazil, none of the polymorphisms tested was associated with the disease. In addition, no transmission distortion was observed in an independent parents-offspring sample from the Azorean Islands. Our data do not support the involvement of the PTGDS gene in the etiology of schizophrenia.

39.	Service, S.; DeYoung, J.; Karayiorgou, M.; Roos, J.L.; Pretorious, H.; Bedoya, G.; Ospina, J.; Ruiz-Linares, A.; Macedo, A.; Palha, J.A.; Heutink, P.; Aulchenko, Y.; Oostra, B.; Van Duijn, C; Jarvelin, M.-R.; Varilo, T.; Peddle, L.; Rahman, P.; Piras, G.; Monne, M.; Murray, S.; Galver, L.; Peltonen, L.; Sabatti, C.; Collins, A.; Freimer, N.. 2006. "Magnitude and distribution of linkage disequilibrium in population isolates and implications for genome-wide association studies", Nature Genetics 38, 5: 556 - 560. The genome-wide distribution of linkage disequilibrium (LD) determines the strategy for selecting markers for association studies, but it varies between populations. We assayed LD in large samples (200 individuals) from each of 11 well-described population isolates and an outbred European-derived sample, using SNP markers spaced across chromosome 22. Most isolates show substantially higher levels of LD than the outbred sample and many fewer regions of very low LD (termed 'holes'). Young isolates known to have had relatively few founders show particularly extensive LD with very few holes; these populations offer substantial advantages for genome-wide association mapping.

40.	Pato, C.N.; Middleton, F.A.; Gentile, K.L.; Morley, C.P.; Medeiros, H.; Macedo, A.; Azevedo, M.H.; Pato, M.T.. 2005. "Genetic linkage of bipolar disorder to chromosome 6q22 is a consistent finding in Portuguese subpopulations and may generalize to broader populations", American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 134, 1: 119 - 121. Abstract We recently reported genome-wide significant linkage to chromosome 6q for bipolar disorder, in a study of 25 Portuguese families, using the Human Mapping Assay Xba 131 (HMA10K). To explore the generalizability of this finding, we reanalyzed our SNP linkage data according to the families' geographic origin. Specifically, the 25 families included 20 families from the Portuguese island collection (PIC; 15 families from the Azores Islands and 5 from the Madeira Islands) and 5 families from continental Portugal. Non-parametric linkage analysis (NPL) was performed as previously described and indicated that each of these subpopulations showed evidence of linkage for the same region. To further address the potential generalizability of these findings to other populations, we have also examined allelic heterozygosity in our subpopulations and in three reference populations (Caucasian, East Asian, and African-American). This analysis indicated that the PIC population is highly correlated to the Caucasian reference population (R = 0.86) for all of chromosome 6. In contrast allelic heterozygosity was more weakly correlated between PIC and both East Asian (R = 0.37) and African-American (R = 0.32) reference populations. Taken together these observations suggest a shared genetic liability among Portuguese populations for bipolar disorder on chromosome 6q, and that the PIC population is likely representative of Caucasians in general.

41.	Middleton, F.A.; Pato, C.N.; Gentile, K.L.; McGann, L.; Brown, A.M.; Trauzzi, M.; Diab, H.; Morley, C.P.; Medeiros, H.M.; Macedo, A.; Azevedo, M.H.; Pato, M.T.. 2005. "Gene Expression Analysis of Peripheral Blood Leukocytes from Discordant Sib-pairs with Schizophrenia and Bipolar Disorder Reveals Points of Convergence between Genetic and Functional Genomic Approaches", American Journal of Medical Genetics Part B: Neuropsychiatric Genetics 136, 1: 12 - 25. Abstract We performed global RNA transcript analysis and comprehensive gene group analysis of peripheral blood leukocyte (PBL) RNA from two groups of matched sib-pairs that were discordant for either schizophrenia (n = 33 sib-pairs) or bipolar disorder (n = 5 sib-pairs). The pairs chosen for these analyses were selected from families with known patterns of genetic linkage (5q for schizophrenia and 6q for bipolar disorder). At the single gene level, we obtained lists of the transcripts with the most significant changes in expression and from these lists determined those with the highest degree of predictive power for classifying subjects according to diagnosis in these samples. At the gene group level, we comprehensively analyzed pairwise expression changes of more than 4,000 functional groups and cytogenetic locations, and present a novel method of displaying these data that we term "cytogenomic" mapping. Verification of selected changes in expression was performed using quantitative real-time RT-PCR. Our results provide compelling evidence for the utility of analyzing PBL RNA for changes in expression in neuropsychiatric disorders.

42.	Petryshen, T.L.; Middleton, F.A.; Tahl, A.R.; Rockwell, G.N.; Purcell, S.; Aldinger, K.A.; Kirby, A.N.; Morley, C.P.; McGann, L.; Gentile, K.L.; Waggoner, S.G.; Medeiros, H.M.; Carvalho, C.; Macedo, A.; Albus, M.; Maier, W.; Trixler, M.; Eichhammer, P.; Schwab, S.G.; Wildenauer, D.B.; Azevedo, M.H.; Pato, M.T.; Pato, C.N.; Daly, M.J.; Sklar, P.. 2005. "Genetic Investigation of Chromosome 5q GABAA Receptor Subunit Genes in Schizophrenia", Molecular Psychiatry 10, 12: 1074 - 1088. Abstract We previously performed a genome-wide linkage scan in Portuguese schizophrenia families that identified a risk locus on chromosome 5q31-q35. This finding was supported by meta-analysis of 20 other schizophrenia genome-wide scans that identified 5q23.2-q34 as the second most compelling susceptibility locus in the genome. In the present report, we took a two-stage candidate gene association approach to investigate a group of gamma-aminobutyric acid (GABA) A receptor subunit genes (GABRA1, GABRA6, GABRB2, GABRG2, and GABRP) within our linkage peak. These genes are plausible candidates based on prior evidence for GABA system involvement in schizophrenia. In the first stage, associations were detected in a Portuguese patient sample with single nucleotide polymorphisms (SNPs) and haplotypes in GABRA1 (P=0.00062-0.048), GABRP (P=0.0024-0.042), and GABRA6 (P=0.0065-0.0088). The GABRA1 and GABRP findings were replicated in the second stage in an independent German family-based sample (P=0.0015-0.043). Supportive evidence for association was also obtained for a previously reported GABRB2 risk haplotype. Exploratory analyses of the effects of associated GABRA1 haplotypes on transcript levels found altered expression of GABRA6 and coexpressed genes of GABRA1 and GABRB2. Comparison of transcript levels in schizophrenia patients and unaffected siblings found lower patient expression of GABRA6 and coexpressed genes of GABRA1. Interestingly, the GABRA1 coexpressed genes include synaptic and vesicle-associated genes previously found altered in schizophrenia prefrontal cortex. Taken together, these results support the involvement of the chromosome 5q GABAA receptor gene cluster in schizophrenia, and suggest that schizophrenia-associated haplotypes may alter expression of GABA-related genes.

43.	Pato, Carlos N; Pato, M.T.; Kirby, A.; Petryshen, T.L.; Medeiros, H.; Carvalho, C.; Macedo, A.; Dourado, A.; Coelho, I.M.; Valente, J.; Soares, M.J.; Ferreira, C.P.; Lei, M.; Verner, A.; Hudson, T.J.; Morley, C.P.; Kennedy, J.L.; Azevedo, M.H.; Daly, M.J.; Sklar, P.. 2004. "Genome-wide scan in Portuguese Island families implicates multiple loci in bipolar disorder: Fine mapping adds support on chromosomes 6 and 11", American Journal of Medical Genetics 127, 1: 30 - 34. Abstract As part of an extensive study in the Portuguese Island population of families with multiple patients suffering from bipolar disorder and schizophrenia, we performed an initial genome-wide scan of 16 extended families with bipolar disorder that identified three regions on chromosomes 2, 11, and 19 with genome-wide suggestive linkage and several other regions, including chromosome 6q, also approached suggestive levels of significance. Dick et al. [2003: Am J Hum Genet 73:107-114] recently reported in a study of 250 families with bipolar disorder a maxLOD score of 3.61 near marker D6S1021 on chromosome 6q. This study replicates this finding having detected a peak NPL = 2.02 (P = 0.025) with the same marker D6S1021(104.7 Mb). Higher-density mapping provided additional support for loci on chromosome 6 including marker D6S1021 with an NPL = 2.59 (P = 0.0068) and peaking at marker D6S1639 (125 Mb) with an NPL = 3.06 (P = 0.0019). A similar pattern was detected with higher-density mapping of chromosome 11 with an NPL = 3.15 (P = 0.0014) at marker D11S1883 (63.1 Mb). Simulations at the density of our fine mapping data indicate that less than 1 scan out of 10 would find two such scores genome-wide in the same scan by chance. Our findings provide additional support for a susceptibility locus for bipolar disorder on 6q, as well as, suggesting the importance of denser scans. Published 2004 Wiley-Liss, Inc.

44.	Middleton, F.A.; Pato, M.T.; Gentile, K.L.; Morley, C.P.; Zhao, X.; Eisener, A.F.; Brown, A.; Petryshen, T.L.; Kirby, A.N.; Medeiros, H.; Carvalho, C.; Macedo, A.; Dourado, A.; Coelho, I.M.; Valente, J.; Soares, M.J.; Ferreira, C.P.; Lei, M.; Azevedo, M.H.; Kennedy, J.L.; Daly, M.J.; Sklar, P.; Pato, C.N.. 2004. "Genomewide Linkage Analysis of Bipolar Disorder by Use of a High-Density Single-Nucleotide–Polymorphism (SNP) Genotyping Assay: A Comparison with Microsatellite Marker Assays and Finding of Significant Linkage to Chromosome 6q22", The American Journal of Human Genetics 74, 5: 886 - 897. Abstract We performed a linkage analysis on 25 extended multiplex Portuguese families segregating for bipolar disorder, by use of a high-density single-nucleotide–polymorphism (SNP) genotyping assay, the GeneChip Human Mapping 10K Array (HMA10K). Of these families, 12 were used for a direct comparison of the HMA10K with the traditional 10-cM microsatellite marker set and the more dense 4-cM marker set. This comparative analysis indicated the presence of significant linkage peaks in the SNP assay in chromosomal regions characterized by poor coverage and low information content on the microsatellite assays. The HMA10K provided consistently high information and enhanced coverage throughout these regions. Across the entire genome, the HMA10K had an average information content of 0.842 with 0.21-Mb intermarker spacing. In the 12-family set, the HMA10K-based analysis detected two chromosomal regions with genomewide significant linkage on chromosomes 6q22 and 11p11; both regions had failed to meet this strict threshold with the microsatellite assays. The full 25-family collection further strengthened the findings on chromosome 6q22, achieving genomewide significance with a maximum nonparametric linkage (NPL) score of 4.20 and a maximum LOD score of 3.56 at position 125.8 Mb. In addition to this highly significant finding, several other regions of suggestive linkage have also been identified in the 25-family data set, including two regions on chromosome 2 (57 Mb, NPL = 2.98; 145 Mb, NPL = 3.09), as well as regions on chromosomes 4 (91 Mb, NPL = 2.97), 16 (20 Mb, NPL = 2.89), and 20 (60 Mb, NPL = 2.99). We conclude that at least some of the linkage peaks we have identified may have been largely undetected in previous whole-genome scans for bipolar disorder because of insufficient coverage or information content, particularly on chromosomes 6q22 and 11p11.

45.	Wong, A.H.C.; Trakalo, J.; Likhodi, O.; Yusuf, M.; Macedo, A.; Azevedo, M.H.; Klempan, T.; Pato, M.T.; Honer, W.G.; Pato, C.N.; Van Tol, H; Kennedy, J.L.. 2004. "Association Between Schizophrenia and the Syntaxin 1A Gene", Biological Psychiatry 56, 1: 24 - 29. Abstract BACKGROUND: Both microarray and candidate molecule studies have demonstrated that protein and mRNA expression of syntaxin and other genes involved in synaptic function are altered in the cerebral cortex of patients with schizophrenia. METHODS: Genetic association between polymorphic markers in the syntaxin 1A gene and schizophrenia was assessed in a matched case-control sample of 192 pairs, and in an independent sample of 238 nuclear families. RESULTS: In the family-based sample, a significant genetic association was found between schizophrenia and one of the four single nucleotide polymorphisms (SNPs) tested: an intron 7 SNP (transmission disequilibrium test TDT chi(2) = 5.898; df = 1; p =.015, family-based association test FBAT z = 2.280, p =.023). When the results for the TDT and case-control analyses were combined, the association was stronger (n = 430; z(c) = 2.859; p =.004). Haplotype analysis supported the association with several significant values that appear to be driven by the intron 7 SNP. Conclusions: The results should be treated with caution until replicated, but this is the first report of a genetic association between syntaxin 1A and schizophrenia.

46.	Ambrósio, A.; Kennedy, J.L.; Macciardi, F.; Macedo, A.; Valente, J.; Dourado, A.; Oliveira, C.R.; Pato, C.N.. 2004. "Family Association Study Between DRD2 and DRD3 Gene Polymorphisms and Schizophrenia in a Portuguese Population", Psychiatry Research 125, 3: 185 - 191. Abstract Schizophrenia is a highly heritable condition, as demonstrated in family, twin and adoption studies. Candidate genes from the dopaminergic system have long been hypothesized to be involved in the etiology of this disorder. In the present study, we investigated the genetic association between polymorphisms in the D2 and D3 dopamine receptor (DRD2, DRD3) genes and schizophrenia. We examined 90 trios from Portugal, and negative results were obtained from association studies with both Haplotype Relative Risk (HRR) and Transmission Disequilibrium Test (TDT), as well as TRANSMIT. Therefore, we conclude that neither the DRD2 nor the DRD3 gene polymorphisms investigated are associated with schizophrenia in our sample.

47.	Petryshen, T.L.; Middleton, F.A.; Kirby, A.N.; Aldinger, K.A.; Purcell, S.; Tahl, A.R.; Morley, C.P.; McGann, L.; Gentile, K.L.; Rockwell, G.N.; Medeiros, H.; Carvalho, C.; Macedo, A.; Dourado, A.; Valente, J.; Ferreira, C.P.; Patterson, N.J.; Azevedo, M.H.; Daly, M.J.; Pato, C.N.; Pato, M.T.; Sklar, P.. 2004. "Support for involvement of neuregulin 1 in schizophrenia pathophysiology", Molecular Psychiatry 10, 4: 366 - 374. Abstract Schizophrenia is a common, multigenic psychiatric disorder. Linkage studies, including a recent meta-analysis of genome scans, have repeatedly implicated chromosome 8p12-p23.1 in schizophrenia susceptibility. More recently, significant association with a candidate gene on 8p12, neuregulin 1 (NRG1), has been reported in several European and Chinese samples. We investigated NRG1 for association in schizophrenia patients of Portuguese descent to determine whether this gene is a risk factor in this population. We tested NRG1 markers and haplotypes for association in 111 parent-proband trios, 321 unrelated cases, and 242 control individuals. Associations were found with a haplotype that overlaps the risk haplotype originally reported in the Icelandic population ('HapICE'), and two haplotypes located in the 3' end of NRG1 (all P<0.05). However, association was not detected with HapICE itself. Comparison of NRG1 transcript expression in peripheral leukocytes from schizophrenia patients and unaffected siblings identified 3.8-fold higher levels of the SMDF variant in patients (P=0.039). Significant positive correlations (P<0.001) were found between SMDF and HRG-beta 2 expression and between HRG-gamma and ndf43 expression, suggesting common transcriptional regulation of NRG1 variants. In summary, our results suggest that haplotypes across NRG1 and multiple NRG1 variants are involved in schizophrenia.

48.	Ruano, D.; Macedo, A.; Dourado, A.; Soares, M.J.; Valente, J.; Coelho, I.M.; Santos, V.; Azevedo, M. H. P; Goodman, A.B.; Hutz, M.H.; Gama, C.G.; Lobato, M.I.; Belmonte-de-Abreu, P.; Palha, J.A.. 2004. "NR4A2 and schizophrenia: Lack of association in a Portuguese/Brazilian study", American Journal of Medical Genetics 128, 1: 41 - 45. The present study investigates the association of mutations in the nuclear receptor NR4A2 in schizophrenic patients. The human Nur-related receptor 1, NR4A2, is an orphan nuclear receptor that can be constitutively active as a transcription factor and for which no natural ligand has yet been identified. Alone or with retinoid X receptor, RXR, NR4A2 influences the expression of several genes important for human brain development and regulation. In the absence of Nurr1 (the mouse homologue to human NR4A2), ventral mesencephalic dopaminergic mouse neurons evidence severe developmental failure, a condition that is lethal soon after birth. Nurr1 involvement in the dopaminergic system makes it a good candidate for study in neuropsychiatric disorders such as schizophrenia and Parkinson disease. Evidence by others support this hypothesis (1) mapping of the NR4A2 gene to chromosome 2q22-23, a region with suggestive linkage to schizophrenia and (2) identification of mutations in patients with schizophrenia (c.366-369delTAC, c.308A>G, c.-469delG),manic depression (c.289A> G),andfamilial Parkinson’s disease (c.-291delT, c.- 245T>G). To further extend these observations, we searched for all these mutations in 176 Caucasian Portuguese and 82 Caucasian Brazilian subjects with lifetime diagnosis of schizophrenia. The study failed to identify any of the described mutations in patients or controls. Nevertheless, these negative results do not exclude altered expression of nuclear receptors in schizophrenia or the presence of other mutations. .

49.	Wong, A.H.C.; Macciardi, F.; Klempan, T.; Kawczynski, W.; Barr, C.L.; Lakatoo, S.; Wong, M.; Buckle, C.; Trakalo, J.; Boffa, E.; Oak, J.; Azevedo, M.H.; Dourado, A.; Coelho, I.M.; Macedo, A.; Vicente, A.; Valente, J.; Ferreira, C.P.; Pato, M.T.; Pato, C.N.; Kennedy, J.L.; Van Tol, H. 2003. "Identification of candidate genes for psychosis in rat models, and possible association between schizophrenia and the 14-3-3¿ gene", Molecular Psychiatry 8, 2: 156 - 166. Abstract Although the genetic contribution to schizophrenia is substantial, positive findings in whole-genome linkage scans have not been consistently replicated. We analyzed gene expression in various rat conditions to identify novel candidate genes for schizophrenia. Suppression subtraction hybridization (SSH), with polyA mRNA from temporal and frontal cortex of rats, was used to identify differentially expressed genes. Expression of mRNA was compared between adult Lewis and Fischer 344 (F344) rats, adult and postnatal day 6 (d6) F344, and adult F344 treated with haloperidol or control vehicle. These groups were chosen because each highlights a particular aspect of schizophrenia: differences in strain vulnerability to behavioral analogs of psychosis; factors that may relate to disease onset in relation to CNS development; and improvement of symptoms by haloperidol. The 14-3-3 gene family, as represented by 14-3-3 and 14-3-3 isoforms in the SSH study, and SNAP-25 were among the candidate genes. Genetic association between schizophrenia and the 14-3-3 gene, positioned close to a genomic locus implicated in schizophrenia, and SNAP-25 genes was analyzed in 168 schizophrenia probands and their families. These findings address three different genes in the 14-3-3 family. We find a significant association with schizophrenia for two polymorphisms in the 14-3-3 gene: a 7 bp variable number of tandem repeats in the 5' noncoding region (P=0.036, 1 df), and a 3' untranslated region SNP (753G/A) that is an RFLP visualized with Ava II (P=0.028). There was no significant genetic association with SNAP-25. The candidate genes identified may be of functional importance in the etiology, pathophysiology or treatment response of schizophrenia or psychotic symptoms. This is to our knowledge the first report of a significant association between the 14-3-3-chain gene and schizophrenia in a family-based sample, strengthening prior association reports in case–control studies and microarray .

50.	Sklar, P.; Pato, M.T.; Kirby, A.N.; Petryshen, T.L.; Medeiros, H.M.; Carvalho, C.; Macedo, A.; Dourado, A.; Coelho, I.M.; Valente, J.; Soares, M.J.; Ferreira, C.P.; Lei, M.; Verner, A.; Hudson, T.J.; Morley, C.P.; Kennedy, J.L.; Azevedo, M.H.; Lander, E.; Daly, M.J.; Pato, C.N.. 2003. "Genome-Wide Scan in Portuguese Island Families Identifies 5q31–5q35 as a Susceptibility Locus for Schizophrenia and Psychosis", Molecular Psychiatry 9, 2: 213 - 218. Abstract: Schizophrenia is a common psychiatric disorder with a complex genetic etiology. To understand the genetic basis of this syndrome in Portuguese Island populations, we performed a genome-wide scan of 29 families with schizophrenia, which identified a single region on 5q31–5q35 with strong linkage (NPL=3.09, P=0.0012 at D5S820). Empirical simulations set a genome-wide threshold of NPL=3.10 for significant linkage. Additional support for this locus in schizophrenia comes from higher-density mapping and mapping of 11 additional families. The combined set of 40 families had a peak NPL=3.28 (P=0.00066) at markers D5S2112–D5S820. These data and previous linkage findings from other investigators provide strong and consistent evidence for this genomic region as a susceptibility locus for schizophrenia. Exploratory analyses of a novel phenotype, psychosis, in families with schizophrenia and bipolar disorder detected evidence for linkage to the same markers as found in schizophrenia (peak NPL=3.03, P=0.0012 at D5S820), suggesting that this locus may be responsible for the psychotic symptoms observed in both diseases.

51.	Schindler, K.M.; Pato, M.T.; Dourado, A.; Macedo, A.; Azevedo, M.H.; Kennedy, J.L.; Pato, C.N.. 2002. "Association and linkage disequilibrium between a functional polymorphism of the dopamine-2 receptor gene and schizophrenia in a genetically homogeneous Portuguese population", Molecular Psychiatry 7, 9: 1002 - 1005. Abstract A functional polymorphism in the promoter region of the DRD2 gene has been found to be associated with schizophrenia in Japanese1,2 and Swedish populations.3 We attempted to replicate these findings in a genetically homogenous Portuguese population using a family-based study design. Analysis of 78 trios revealed evidence for association between the -141 C Ins allele and schizophrenia using the haplotype relative risk (HRR) method (2 = 9.30, P = 0.0023). Further examination of this sample using an alternative family-based association analysis method, the transmission disequilibrium test (TDT), of 33 informative matings from the Portuguese trios provided evidence for an allelic association and linkage disequilibrium between the insertion allele and schizophrenia (2 = 8.76, P = 0.0031). These consistent results using two alternative family-based association analysis methods replicate the findings of previous reports, and thus further implicate a potential role for the dopamine-2 receptor in the genetic etiology of schizophrenia.

52.	Xu, J.; Pato, M.T.; Torre, C.D.; Medeiros, H.; Carvalho, C.; Basile, V.S.; Bauer, Amy; Dourado, A.; Valente, J.; Soares, M.J.; Macedo, A.; Coelho, I.M.; Ferreira, C.P.; Azevedo, M.H.; Macciardi, F.; Kennedy, J.L.; Pato, C.N.. 2001. "Evidence for linkage disequilibrium between the alpha 7-nicotinic receptor gene (CHRNA7) locus and schizophrenia in Azorean families", American Journal of Medical Genetics 105, 8: 669 - 674. Abstract Recent studies have suggested that the alpha 7-nicotinic receptor gene (CHRNA7) may play a role in the pathogenesis of schizophrenia. The alpha 7-nicotinic receptor gene (CHRNA7) is involved in P50 auditory sensory gating deficits, and the genomic locus for this gene lies in the chromosome 15q13-14 regions. The human gene is partially duplicated (exons 5-10) with four novel upstream exons. The marker D15S1360 has been shown to be significantly linked with the phenotype of abnormal P50 suppression in schizophrenia families. The marker L76630 is 3 kb in the 3' direction from the last exon of the CHRNA7 gene and is located in the duplicated region. The function of the two L76630 copies is unknown. We genotyped three polymorphic markers D15S1360, D15S165, and L76630 that are localized in a genomic fragment containing the CHRNA7 in 31 Azorean schizophrenia families/trios (including 41 schizophrenia individuals and 97 unaffected families members). An overall analysis utilizing the family-based association test revealed significant linkage disequilibrium between L76630 and schizophrenia (P = 0.0004). Using the extended transmission disequilibrium test and limiting the analysis to one triad per family, transmission disequilibrium of D15S1360 was near significance (P = 0.078). The 15q13 region overlaps with the location of two well-known genomically imprinted disorders: Angelman syndrome and Prader-Willi syndrome. Therefore, we investigated maternal and paternal meioses. We found significant transmission disequilibrium for D15S1360 through paternal transmission (P = 0.0006) in our schizophrenia families. The L76630 marker showed a significant disequilibrium in maternal transmissions (P = 0.028). No parent-of-origin effect was found in D15S165. Overall, our results suggest that the CHRNA7 may play a role in schizophrenia in these families. A parent of origin effect may be present and requires further study.

53.	Xu, J.; Pato, M.T.; DallaTorre, C.; Bauer, A.; Li, D.; Basile, V.S.; Macedo, A.; Dourado, A.; Valente, J.; Kennedy, J.L.; Pato, C.N.. 2001. "Investigation of Repeat Sizes at CAG/CTG Loci SCA2, SCA8, ERDA1 and SEF2-1B associated with schizophrenia and bipolar affective disorder in the Portuguese Population", Primary Psychiatry, 8, 9: 54 - 59.

54.	Ambrósio, A.; Kennedy, J.L.; Macciardi, F.; Macedo, A.; Azevedo, M.H.; Oliveira, C.R.; Pato, M.T.; Schindler, K.M.; Pato, C.N.. 2001. "Candidate Gene Studies of Bipolar Disorder with further Linkage Analysis of Serotonergic System Genes in a Portuguese Population", Primary Pychiatry 8, 9: 61 - 64.

55.	Dourado, A.; Azevedo, M.H.; Macedo, A.; Coelho, I.M.; Valente, J.; Soares, M.J.; Pires, A.L.; Pato, M.T.; Pato, C.N.. 2001. "A Look at the Influence of Genetics in Psychiatry: Reduced Prevalence of Psychoses in Santa Maria Island, Azores, Portugal", Primary Pychiatry 8, 9: 34 - 37.

56.	Vincent, John B; Neves-Pereira, Maria L; Paterson, Andrew D; Yamamoto, Etsuko; Parikh, Sagar V; Macciardi, Fabio; Gurling, Hugh M; Potkin, Steve G; Pato, C.N.; Macedo, A.; Kovacs, Maria; Davies, Marilyn; Lieberman, Jeffrey A; Meltzer, Herbert Y; Petronis, Arturas; Kennedy, James L. 2000. "An Unstable Trinucleotide-Repeat Region on Chromosome 13 Implicated in Spinocerebellar Ataxia: A Common Expansion Locus", The American Journal of Human Genetics 66, 3: 819 - 829. Larger CAG/CTG trinucleotide-repeat tracts in individuals affected with schizophrenia (SCZ) and bipolar affective disorder (BPAD) in comparison with control individuals have previously been reported, implying a possible etiological role for trinucleotide repeats in these diseases. Two unstable CAG/CTG repeats, SEF2-1B and ERDA1, have recently been cloned, and studies indicate that the majority of individuals with large repeats as detected by repeat-expansion detection (RED) have large repeat alleles at these loci. These repeats do not show association of large alleles with either BPAD or SCZ. Using RED, we have identified a BPAD individual with a very large CAG/CTG repeat that is not due to expansion at SEF2-1B or ERDA1. From this individual’s DNA, we have cloned a highly polymorphic trinucleotide repeat consisting of (CTA)n (CTG)n, which is very long (~1,800 bp) in this patient. The repeat region localizes to chromosome 13q21, within 1.2 cM of fragile site FRA13C. Repeat alleles in our sample were unstable in 13 (5.6%) of 231 meioses. Large alleles (>100 repeats) were observed in 14 (1.25%) of 1,120 patients with psychosis, borderline personality disorder, or juvenile-onset depression and in 5 (.7%) of 710 healthy controls. Very large alleles were also detected for Centre d’Etude Polymorphisme Humaine (CEPH) reference family 1334. This triplet expansion has recently been reported to be the cause of spinocerebellar ataxia type 8 (SCA8); however, none of our large alleles above the disease threshold occurred in individuals either affected by SCA or with known family history of SCA. The high frequency of large alleles at this locus is inconsistent with the much rarer occurrence of SCA8. Thus, it seems unlikely that expansion alone causes SCA8; other genetic mechanisms may be necessary to explain SCA8 etiology.

57.	Vincent, John B; Yuan, Qiu-Ping; Schalling, Martin; Adolfsson, R; Azevedo, M.H.; Macedo, A.; Bauer, Amy; DallaTorre, Camille; Medeiros, Helena M; Pato, M.T.; Pato, C.N.; Bowen, Timothy; Guy, Carol A; Owen, Michael J; O'Donovan, Michael C; Paterson, Andrew D; Petronis, Arturas; Kennedy, James L. 2000. "Long Repeat Tracts at SCA8 in Major Psychosis", American Journal of Medical Genetics 96, 6: 873 - 876. Abstract Expansion at a recently identified unstable trinucleotide repeat on chromosome 13q21 has been reported as the molecular cause for spinocerebellar ataxia type 8 (SCA8). The trinucleotide repeat, which consists of a [CTA]n repeat and adjacent [CTG]n repeat, was reported to have a pathogenic range of 107–127 CTG repeats (or 110–130 combined CTA and CTG repeats) in a large ataxia kindred. This repeat region was also cloned by our group from a bipolar affective disorder (BPAD) patient, who has approximately 600 combined repeats, and large alleles (>100 repeats) were reported to be present in 0.7% of controls and 1.5% of major psychosis patients (n = 710 and n = 1,120, respectively). We have followed up these findings by screening three new samples of BPAD and schizophrenia (SCZ) patients and controls, including 272 individuals from 14 BPAD families from Sweden, 130 individuals from 32 SCZ and BPAD families/trios from the Azores Islands, and 206 SCZ individuals from the United Kingdom and Ireland, and 219 matched controls. We found large repeat alleles above the SCA8 pathogenic range in individuals from 3 of 32 Azorean pedigrees and in 1 of 206 SCZ individuals from the United Kingdom, and repeat alleles within the SCA8 pathogenic range in 1 of 14 Swedish families. Although the rarity of major psychosis patients carrying the SCA8 expansion mutation would require a much larger sample size to reach statistical significance, these results support the previously reported observation of increased occurrence of large repeats at SCA8 in major psychosis. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:873–876, 2000. © 2000 Wiley-Liss, Inc.

58.	Pato, C.N.; Macedo, A.; Ambrósio, A.; Vincent, J.B.; Bauer, A.; Schindler, K.M.; Xu, J.; Coelho, I.M.; Dourado, A.; Valente, J.; Azevedo, M.H.; Kennedy, J.L.; Pato, M.T.. 2000. "Detection of Expansion Regions in Portuguese Bipolar Families", American Journal of Medical Genetics 96, 6: 854 - 857. Abstract We have studied 24 families with multiple affected members with bipolar disorder to test the hypothesis that in those families clinically showing genetic anticipation [Macedo et al., 1999] we would find large repeat expansions. The families meeting inclusion criteria had a minimum of two affected members over two generations and showed marked anticipation both in terms of age of onset and disease severity. We used the repeat expansion detection (RED) method to test patients (n = 24) and controls from these families and unrelated controls (n = 53). We also genotyped patients and family members from two families with large expansions at the known expansion loci on chromosomes 13, 17, and 18. The RED method revealed a higher number of large expansions in patients compared with controls (t-test; P < 0.0055: Mann-Whitney U; P = 0.02). The patients with the largest expansions were typed at the specific loci on chromosomes 13, 17, and 18 and the chromosome 18 expansion locus segregated with disease in one family, and a second family showed segregation with the expansion located at the SCA8 locus on chromosome 13. Genetic anticipation had been analyzed in this cohort of families, with correction for potential ascertainment bias, possible proband effects, cohort effects, regression to the mean, gender effects, and maternal vs. paternal transmission. None of these potential confounds appeared to account for the observed anticipation. We also identified that the presence of large expansions in affected family members derives primarily from two families from the genetically isolated Azores population. One family shows segregation with the chromosome 18 locus, whereas the other family segregates with expansions at the SCA8 locus. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:854–857, 2000. © 2000 Wiley-Liss, Inc.

59.	Azevedo, M.H.; Soares, M.J.; Coelho, I.M.; Dourado, A.; Valente, J.; Macedo, A.; Pato, M.T.; Pato, C.N.. 1999. "Using Consensus OPCRIT Diagnoses. An Efficient Procedure for Best-Estimate Lifetime Diagnoses", The British Journal of Psychiatry 175, 2: 154 - 157. Abstract BACKGROUND: The Operational Criteria Checklist (OPCRIT) generates diagnoses according to 12 operational diagnostic systems (e.g. DSM-III, DSM-III-R, Research Diagnostic Criteria, ICD-10). AIMS: To examine the agreement between diagnoses generated by the OPCRIT, as completed by the interviewer, with a best-estimate lifetime procedure using the OPCRIT. METHOD: Subjects came from large multi-generational bipolar or schizophrenia pedigrees (n = 100), and from a sample of unrelated subjects with schizophrenia (n = 40). We analysed the diagnostic agreement between OPCRIT diagnoses generated by the interviewer and our best-estimate OPCRIT diagnoses, according to DSM-III-R and ICD-10, using Cohen kappa statistics. RESULTS: Excellent agreement was found between interviewer OPCRIT diagnoses and OPCRIT diagnoses made by the best-estimate lifetime consensus procedure for DSM-III-R (kappa = 0.83) and ICD-10 (kappa = 0.81). CONCLUSIONS: Results suggest that this procedure for diagnostic assessment is an efficient alternative to classic best-estimate diagnosis procedures.

60.	Macedo, A.; Azevedo, M.H.; Coelho, I.M.; Dourado, A.; Valente, J.; Pato, M.T.; Soares, M.J.; Kennedy, J.L.; Macciardi, F.; Pato, C.N.. 1999. "Genetic Anticipation in Portuguese Families with Bipolar Mood Disorder", CNS SPECTRUMS 4, 5: 25 - 31.

61.	Souery, D.; Lipp, O.; Mahieu, B.; Serretti, A.; Cavallini, C.; Ackenheil, M.; Adolfsson, R.; Aschauer, H.; Blackwood, D.; Dam, H.; Verheyen, G.; Delcoigne, B.; De Martelaer, V; Dikeos, D.; Fuchshuber, S.; Heiden, M.; Jablensky, A.; Jakovljevic, M.; Kessing, L.; Lerer, B.; Macedo, A.; Mellerup, T.; Milanova, V.; Muir, W.J.; Nylander, P.-O.; Oruc, L.; Papadimitriou, G.N.; Pekkarinen, P.; Peltonen, L.; Azevedo, M.H.; Pull, C.; Shapira, B.; Smeraldi, E.; Staner, L.; Stefanis, C.; Verga, M.; Raeymaekers, P.; Macciardi, F.; Van Broeckhoven, C; Mendlewicz, J.. 1998. "European Collaborative Project on Affective Disorders: Interactions Between Genetic and Psychosocial Vulnerability Factors", Psychiatric Genetics 8, 4: 197 - 205. Abstract: Despite strong evidence provided by genetic epidemiology of genetic involvement in the aetiology of bipolar and unipolar affective disorders, the exact nature of the predisposing gene(s) is still being investigated through linkage and association studies. The interaction of susceptibility genes and environmental factors in these diseases is also of fundamental importance and requires proper investigation. Interesting theories have recently been proposed examining the possible role of various chromosomal regions, candidate genes and mutations in affective disorders. Reliable multicentre-based methodology is currently being employed to examine these theories, with attention given to statistical analysis and the statistical power of the sample. The present article describes the European Collaborative Project on Affective Disorders (ECPAD) 'Interactions between genetic and psychosocial vulnerability factors', involving 15 European centres. A description is given of the association and family samples collected for the project and also the methodology used to analyse interactions in the gene-psychosocial environment. This material provides a powerful tool in the search for susceptibility genes in affective disorders and takes into account non-genetic aetiological factors.

62.	Pato, Carlos N; Azevedo, M.H.; Pato, M.T.; Kennedy, J.L.; Coelho, I.M.; Dourado, A.; Macedo, A.; Valente, J.; Ferreira, C.P.; Madeira, Jose; Camara, J.G.; Moniz, M.; Correia, C.. 1997. "Selection of Homogeneous Populations for Genetic Study: The Portugal Genetics of Psychosis Project", American Journal of Medical Genetics 74, 3: 286 - 288. Abstract Molecular genetic studies of psychiatric disorders must face the possibility that despite the significant contribution of genetic factors to the expression of syndromes like schizophrenia, these syndromes may be a heterogeneous collection of genetic and non-genetic illnesses. These illnesses may be etiologically distinct from each other and still share many clinical features in common. Linkage studies of families with multiple affected members tend to favor the selection of genetic forms of a syndrome but can still represent a heterogeneous set of different genetic illnesses. To limit the potential genetic heterogeneity of a study sample, we selected a population that was geographically isolated and was historically relatively genetically homogeneous. We then assessed the relative level of homogeneity utilizing a surname analysis of the population of the Azores, mainland Portugal, rural USA, and urban USA. The average number of families with the same last name corrected for population size in the Azores is 30.88, in Coimbra it is 21.42, compared to 1.13 in a rural American population and 0.38 in an urban American population. The results of this analysis indicate that the Azores have the highest degree of homogeneity, and mainland Portugal has a high degree of homogeneity. Am. J. Med. Genet. 74:286–288, 1997. © 1997 Wiley-Liss, Inc.

63.	Cardno, A. G; Murphy, K.C.; Jones, L.A.; Guy, C.A.; Asherson, P.; Azevedo, M.H.; Coelho, I.M.; Macedo, A.; Pato, C.N.; McGuffin, P.; Owen, M.J.; O’Donovan, M.C.. 1996. "Expanded CAG/CTG Repeats in Schizophrenia. A Study of Clinical Correlates", The British Journal of Psychiatry 169, 6: 766 - 771. Abstract BACKGROUND: Schizophrenia is associated with expanded CAG/CTG trinucleotide repeats. We wished to determine whether the presence of such expansions correlated with specific subsyndromes or other clinical features of schizophrenia. METHOD: Seventy patients from England and Wales and 44 patients from Portugal with a DSM-III-R diagnosis of schizophrenia were rated on the OPCRIT checklist. Patient's maximum CAG/CTG repeat length was measured using repeat expansion detection (RED). Significant differences were sought for repeat lengths in subjects categorised according to dimensional and categorical schizophrenia subsyndromes, affective episodes, individual symptoms, and a range of demographic variables. RESULTS: Maximum CAG/CTG repeat length did not differ significantly for any of the clinical or demographic variables studied. CONCLUSION: There are no subsyndromes or other clinical features of schizophrenia associated with CAG/CTG repeat expansion. Therefore, the identification of the gene(s) that contain expanded CAG/CTG repeats and which are associated with schizophrenia is unlikely to be facilitated at present by using any subsyndromes of schizophrenia as phenotypes.

64.	O’Donovan, M.C.; Guy, C.A.; Craddock, N.J.; Bowen, T.; McKeon, P.; Macedo, A.; Maier, W.; Wildenauer, D.B.; Aschauer, H.N.; Sorbi, S.; Feldman, E.; Mynett-Johnson, L.; Claffey, E.; Nacmias, B.; Valente, J.; Dourado, A.; Grassi, E.; Lenzinger, E.; Heiden, A.M.; Moorhead, S.; Harrison, D.; Williams, J.; McGuffin, P.; Owen, M. J. 1996. "Confirmation of Association Between Expanded CAG/CTG Repeats and Both Schizophrenia and Bipolar Disorder", Psychological Medicine 26, 06: 1145 - 1145. Synopsis Recent studies have suggested that expanded CAG/CTG repeats contribute to the genetic aetiology of schizophrenia and bipolar disorder. However, the nature of this contribution is uncertain and difficult to predict from other known trinucleotide repeat diseases that display much simpler patterns of inheritance. We have sought to replicate and extend earlier findings using Repeat Expansion Detection in an enlarged sample of 152 patients with schizophrenia, 143 patients with bipolar disorder, and 160 controls. We have also examined DNA from the parents of 62 probands with schizophrenia or bipolar disorder. Our results confirm our earlier, preliminary findings of an association between expanded trinucleotide repeats and both schizophrenia and bipolar disorder. However, our data do not support the hypothesis that trinucleotide repeat expansion can alone explain the complex patterns of inheritance of the functional psychoses neither can this mechanism fully explain apparent anticipation.

65.	Williams, J.; Farmer, A.E.; Ackenheil, M.; Kaufmann, C.A.; McGuffin, P.; Azevedo, M.H.; Macedo, A.; Dourado, A.; Valente, J.. 1996. "A Multicentre Inter-Rater Reliability Study Using the OPCRIT Computerized Diagnostic System", Psychological Medicine 26, 04: 775 - 775. Synopsis We examined the reliability of the OPCRIT system from ratings produced by 30 USA and European clinicians involved in molecular genetic research. The OPCRIT system facilitates a polydiagnostic approach to research on severe psychiatric disorders. OPCRIT comprises a 90-item checklist of signs and symptoms and a suite of computer programs, which together generate diagnoses according to the operational criteria of 12 major classificatory systems (e.g. DSM-III, DSM-III-R, RDC, ICD-10). Thirty summaries of actual cases ranging in signs and symptoms, taken from independent sources, were rated by participants from research centres across Europe and the USA using the OPCRIT system. Each rating was then compared to a standard rating using a kappa statistic. Good levels of reliability were observed within all classifications (e.g. DSM-III-R, kappa = 0·73, RDC, kappa = 0·71; ICD-10, kappa = 0·70) and a similar pattern of ratings was found in both the European and USA samples. We conclude that the OPCRIT system, is both flexible and practicable retaining the ‘top-down’ advantage of operational definitions as well as the ‘bottom-up’ potential offered by well defined signs, symptoms and other component items. Within the limitations of an international, multicentre design this study shows that the OPCRIT system affords good reliability with raters from a variety of geographical and theoretical backgrounds.

Trabalhos completos/resumidos em eventos com arbitragem científica Papers in conference proceedings with scientific refereeing

1.	Pereira, A.T.; Bos, S.C.; Marques, M.; Soares, M.J.; Maia, B.R.; Valente, J.; Nogueira, V.; Macedo, A.; Azevedo, M.H.. 2012. "Development and validation of the Portuguese short version of the Postpartum Depression Screening Scale to screen for antenatal depression", Trabalho apresentado em 20th European Congress of Psychiatry, In European Psychiatry, Praga, República Checa. Introduction: Although developed for postpartum depression, the Postpartum Depression Screening Scale (PDSS; Beck & Gable, 2002) is accurate to screen for antenatal depression (Pereira et al., 2011). Nonetheless, as any screening instrument should be valid, short and easy it is important to develop a PDSS short form to use in pregnancy. Objectives: To develop PDSS short version to use in pregnancy and to determine its cut-off points and associated conditional probabilities to screen for antenatal depression according to DSM-IV and ICD-10 criteria. Methods: 441 pregnant women in their last trimester of pregnancy (M=32.6±3.47 weeks of gestation) completed the Portuguese PDSS adapted to pregnancy and were interviewed using the Mood Disorders Section/Diagnostic Interview for Genetic Studies. A factor analysis was performed to select the items (factor loadings >.60). ROC analysis was applied and cut-off points adjusted to the prevalence were determined. Results: Four factors were extracted, making a total of 24 items selected to the short version (PDSS-24). For major depression/DSM-IV the cut-off point (CO) of 44, resulted in sensitivity 83.3%, specificity 78.9%, positive predictive value (PPV) 8.5% and negative predictive value (NPV) 99.7%; for depressive disorder/ICD-10 the CO of 42 determined sensitivity 85.7%, specificity 79.2%, PPV 11.9%, NPV 99.4%; for mild/moderate depression with somatic syndrome or severe depression without psychotic symptoms/ICD-10 the CO of 46 was associated to sensitivity 87.5%, specificity 82.2%, PPV 9.3% and NPV 99.7%. Conclusions: The PDSS-24 is a good alternative to the 35-items version, equally valid, but more economic, faster and easier.

2.	Pereira, A.T.; Marques, M.; Soares, M.J.; Valente, J.; Nogueira, V.; Bos, S.C.; Maia, B.R.; Macedo, A.; Azevedo, M.H.. 2012. "Worry and rumination: Exploring a brief measure of repetitive thought", Trabalho apresentado em 20th European Congress of Psychiatry, In European Psychiatry, Praga, República Checa. We wanted to explore the validity of measuring the tendency to worry and to overthink, in the Portuguese context. 714 medical students completed the following measures: Worry and Overthinking (two items each) “I worry a lot”, “The people around me consider that I worry a lot”, “I think a lot over things”, “The people around me consider that I think a lot over things”; Eysenck Personality Inventory (EPI) Neuroticism and Extroversion (NE-EPI/E-EPI); Arousal Predisposition Scale (Arousability); Revised NEO Personality Inventory (NEO-PI-R); Neuroticism facets Anxiety, Angry, Depression, Impulsiveness and Vulnerability; Profile of Mood States Positive and Negative Affect (POMS-PA/POMS-NA). Worry and Overthinking were correlated (p< .001). Temporal stability was high (Worry p< .01; Overthinking p< .01; Worry+Overthinking p< .01). The 4 items factor structure yielded a single factor (a=.836). A factor analysis of these items with EPI items showed that they loaded highly (>.50) on the NE-EPI. Worry and Overthinking were positively correlated with negative traits: NE-EPI, Arousability, POMS-NA, Neuroticism-NEO-PI-R (all p< .001) and with NEO-PI-R-N facets: all p values < .001, with the exception of Impulsiveness (p< .05). They were negatively correlated with positive traits: E-EPI and POMS-PA (all p< .001). Based on Worry and Overthinking means and SD and considering frequencies five groups were formed: High worry/overthinking; High worry/low-medium overthinking; Medium worry/overthinking; Low worry/medium-high overthinking; High worry/overthinking. Groups mean comparisons significantly differ in positive and negative traits (means increased/decreased, respectively, from group 1 to 5). We provide preliminary evidence for the usefulness of this measure in this population.

3.	Macedo, A.; Pereira, A.T.; Marques, M.; Soares, M.J.; Valente, J.; Nogueira, V.; Azevedo, M.H.. 2012. "The Portuguese version of the Domains of Perfectionism Scale", Trabalho apresentado em 20th European Congress of Psychiatry, In European Psychiatry, Praga, República Checa. Introduction: The Domains of Perfectionism Scale (DP; Rhéaume et al., 1995) assesses the extent in which the respondent is perfectionist across 22 life domains, using a five-point Likert scale. Objectives: 1. To analyze the psychometric properties and factorial structure of the Portuguese version of the DP scale; 2. To investigate which domains are more prevalent and whether the DP mean scores are affected by gender. Methods: The Portuguese version of DP scale was administered to a sample of 217 university students (Mean age=18.50±2.345). To study the temporal stability, 31 respondents answered the scale again after six weeks. Response options were collapsed into 0 and 1, in order to compute the variable “Number of domains” (NrD). Results: The DP Cronbach's alpha coefficient was .85. The test-retest correlation coefficient for the total score was .98 (p< .001). The factorial analysis resulted in a four factors structure explaining 50.14% of variance: F1 Relationships and Appearance, F2 Studies and Work, F3 Health and Leisure and F4 Order and Domestic Affairs. The most frequent individual domains were Bodily hygiene, Romantic relationships, Work, Social relationships and Studies (>80%). DP total mean score did not significantly differ between genders (Males 66.62 ±10.446 vs. Females 67.83 ± 7.734, p=.525), nor the NrD (15.76 ±2.220 vs. 15.52±4.236, p=.752). The individual domains Studies, Orthography, Presentation of documents and Domestic chores and F2 were significantly higher in females; Sports and F3 were significantly higher in males. Conclusions: The Portuguese version of the DP scale presented good reliability and construct validity.

4.	Macedo, A.; Pereira, A.T.; Amaral, A.P.; Marques, M.; Soares, M.J.; Valente, J.; Nogueira, V.; Azevedo, M.H.. 2012. "Domains of perfectionism", Trabalho apresentado em 20th European Congress of Psychiatry, In European Psychiatry, Praga, República Checa. Introduction: The knowledge about the specificity of perfectionism domains is scarce. Objectives: To explore the extent to which perfectionism is a general personality trait influencing multiple functioning areas rather than a context-specific trait and to investigate the relation between domains of perfectionism and perfectionism dimensions and affect. Methods: 217 University students answered to the Portuguese versions of the Domains of Perfectionism Scale (DP; Rhéaume et al., 1995), Multidimensional Perfectionism Scale (Hewitt and Flett, 1991; MPS-H&F), Multidimensional Perfectionism Scale (Frost et al., 1990; MPS-F) and Profile of Mood States (McNair et al., 1971). Results: On average participants were perfectionists in approximately 15 domains. All the 22 individual domains and the 4 DP factorial scores presented moderate (=.30) to high (=.50) coefficients with the Number of Domains (NrD). Self Oriented Perfectionism (SOP/MPS-H&F), was the perfectionism dimension correlating with most DP variables; Social Prescribed Perfectionism (MPS-H&F) did not significantly correlate with any DP variable. Organization and Personal High Standards (both MPS-F) significantly and positively correlated with several specific domains and with the NrD. Positive Affect (PA), but not Negative Affect, presented positive correlations with almost all DP variables, including NrD. The mean NrD, SOP and PA were significantly higher in subjects who considered themselves highly perfectionist in the most prevalent domains of perfectionism. PA, Organization and SOP were independent significant predictors of the NrD. Conclusions: Perfectionism influence multiple areas; perfectionism expressing in a greater number of life domains seems to be internally motivated and to be associated with positive psychological variables.

5.	Bento, C.; Pereira, A.T.; Saraiva, J.M.; Marques, M.; Soares, M.J.; Bos, S.C.; Valente, J.; Macedo, A.; Azevedo, M.H.. 2012. "Children's Eating Attitudes Test: Psychometric characteristics in a Portuguese adolescent girls Sample", Trabalho apresentado em 20th European Congress of Psychiatry, In European Psychiatry, Praga, República Checa. Introduction: The Children Eating Attitudes Test (ChEAT; Maloney et al. 1988) is a well-established 26-item scale designed to measure a wide range of problematic eating attitudes and behaviours among children and adolescents. Objective: To analyse ChEAT reliability and validity in a Portuguese adolescent girls sample. Method: 565 high-school girls (mean age 15.76±1.571; mean BMI 20.42 ±2.745) answered the Portuguese versions of ChEAT and of the Contour Drawing Figure Rating Scale (CDFRS; Thompson & Gray, 1995). To study the temporal stability 124 girls answered the ChEAT again after approximately six weeks. Results: Cronbach\'s alpha was of .76. The test-retest Pearson correlation was of 0.61. A four factors structure (explained variance=44.06%) was selected: Factor (F) 1 Fear of Getting Fat, F2 Restrictive and Purging Behaviours, F3 Food Preoccupation, F4 Social Pressure to Eat. The body satisfaction as assessed through CDFRS was negatively correlated with the total ChEAT (-.35), F1 (-.47) and F2 (-.23) (all p>.001); and positively correlated with F4 (.26, p< .001). Significant mean differences (all p< .01) were found between the three CDFRS groups (Group -1 Want to be thinner; Group 0 Satisfied; Group 1 Want to be fatter) in all eating behaviour dimension scores, except for F3; total ChEAT, F1 and F2 mean scores between groups significantly decreased through the body satisfaction groups -1, 0 and 1 and significantly increased for F4. Conclusions The Portuguese ChEAT psychometric characteristics are good. Factorial structure is in accordance with the original. It could be very useful to clinical and epidemiological purposes.

6.	Nogueira, V.; Macedo, A.; Pereira, A.T.; Marques, M.; Soares, M.J.; Valente, J.; Azevedo, M.H.. 2012. "Psychometric properties and factor structure of the Portuguese version of The Maudsley Obsessional-Compulsive Inventory. ", Trabalho apresentado em 20th European Congress of Psychiatry. Praga, República Checa, 3-7 Março 2012 , In European Psychiatry, Praga, República Checa. Introduction: The Maudsley Obsessional-Compulsive Inventory (MOCI; Hodgson & Rachman, 1977) continues to be a widely used self-report measure of obsessive-compulsive symptoms. It has been translated into at least seven languages and the respective validations have resulted in good psychometric characteristics. It has not been validated to the Portuguese population yet. Objectives: To investigate the psychometric properties and factorial structure of the MOCI Portuguese version. Methods: The process of translation/ re-translation followed the required steps. The MOCI was administered to a community sample of 217 first year university students (178 girls; 82.0%). The mean age was 18.50 (± 2.345: range: 17-35). To study the temporal stability 166 (135 girls; 81.3%) respondents answered the questionnaires again after approximately six weeks. Results: The MOCI Cronbach's a was good (.79). The test-retest coefficient for the total score was high (.79; p< .001). An inspection of the Cattel's Scree plot and also of the item's content led us to select a three factors structure, which explained variance was of 29.17%: Factor (F) 1 “Doubting and Rumination” (VE=15.43%; a=.72); F2 “Checking” (VE=7.65%; a=.66) and F3 “Cleaning” (VE=6.08%; a=.63). Temporal stability of F1, F2 and F3 were high: .67, .65 and .73 (all p< .001), respectively. Pearson correlations between factors were moderate and significant (=.30). Conclusions: The MOCI Portuguese version has good psychometric properties and its factorial structure is in accordance with those reported by other groups. It could be very useful to clinical and epidemiological purposes, as well as to transcultural studies. .

7.	Nogueira, V.; Valente, J.; Soares, M.J.; Pereira, A.T.; Marques, M.; Azevedo, M.H.; Macedo, A.. 2012. "Suicidal behaviour in schizophrenia - The effect of emotional reactivity and negative symptons", Trabalho apresentado em 20th European Congress of Psychiatry, In European Psychiatry, Praga, República Checa. Introduction: Schizophrenia is a serious and common disease, one of the most disabling mental disorders in developed countries (Azevedo et al., 2010) and it is associated with high suicide attempt rates. A significant percentage of premature deaths is due to suicide and up to 50% of the patients attempt suicide during their lifetime, specially during the earlier course of the disease (Meltzer, 2003). Objectives: In this study, the authors aimed to identify clinical factors (focusing on emotional reactivity and negative symptoms) and social-demographic variables associated to suicidal behaviour in Schizophrenia, in a large sample of Portuguese patients. Methods: 508 patients with a diagnosis of Schizophrenia were selected according ICD-10 diagnostic criteria definitions, using the OPCRIT polydiagnostic system (McGuffin et al., 1991). Clinical and social-demographic variables were extracted from DIGS (Azevedo et al., 1993; Nurnberger et al., 1994). Suicidal Behaviour was assessed with the "Suicidal Behaviour Section" from DIGS. Results: Suicidal behaviour occurred in 21.8% of the patients, with voluntary drug overdosing being the most used method. Although men showed to use more violent methods, the behaviour was more frequent in female patients. There was no association with the severity of delusions or hallucinations. The absence of formal thought changes, emotional withdrawal and affective blunting (meaning greater emotional reactivity) showed to be risk factors for the occurrence of suicidal behaviour. Conclusion: This work may have relevant clinical implications due to its potential to guide the clinician in identifying a suicidal profile among his/her patients with Schizophrenia and delineating early intervention strategies.

8.	Pereira, A.T.; Bos, S.C.; Maia, B.R.; Marques, M.; Soares, M.J.; Gomes, A.A.; Valente, J.; Nogueira, V.; Macedo, A.; Azevedo, M.H.. 2011. "The Portuguese short version of the Postpartum Depression Screening Scale", Trabalho apresentado em 19th European Congress of Psychiatry, In P03-507 The Portuguese short version of the postpartum depression screening scale, Vienna. Introduction: Screening for perinatal depression is essential. The Postpartum Depression Screening Scale (PDSS; Beck & Gable, 2002) is a self-report instrument, composed of 35 items. The Portuguese version of the PDSS revealed to be a valid instrument to screen for perinatal depression (Pereira et al., 2010a,b). Objectives: To develop PDSS short version and to determine its cut-off points and associated conditional probabilities to screen for depression according to DSM-IV and ICD-10 criteria. Methods: Participants were 452 women in their third month post-partum (M = 13.07 weeks post-partum; SD = 1.808). All women completed the Portuguese PDSS and were interviewed using the Mood Disorders Section/Diagnostic Interview for Genetic Studies. To select items for the short version the items that showed the highest correlations with their respective seven dimension scores were retained. ROC analysis was applied and both cut-off points and associated conditional probabilities adjusted to the real prevalence were determined. Results: For major depression/DSM-IV the cut-off point of 15, resulted in sensitivity of 77.8%, specificity of 88.9%, positive predictive value (PPV) of 21.7% and negative predictive value (NPV) of 98.9%; for depressive disorder/ICD-10 the cut-off point of 14 determined sensitivity 77.3%, specificity 84.0%, PPV 19.7%, NPV 98.6%; for mild/moderate depression with somatic syndrome or severe depression without psychotic symptoms/ICD-10 the cut-off point of 18 was associated to sensitivity 91.7%, specificity 94.5%, PPV 31.4% and NPV 99.8%. Conclusions: The Portuguese short version of PDSS is a good alternative to the 35-items version, equally valid and precise, but more economic, faster and easier.

9.	Maia, B.R.; Pereira, A.T.; Marques, M.; Soares, M.J.; Bos, S.C.; Valente, J.; Gomes, A.A.; Nogueira, V.; Azevedo, M.H.; Macedo, A.. 2011. "Perfeccionism role in perinatal depression (ICD-10, DSM-IV and BDI-II, PDSS) ", Trabalho apresentado em 19th European Congress of Psychiatry, In P03-509 - The role of perfectionism in perinatal depression (ICD-10, DSM-IV and BDI-II, PDSS), Vienna. Aims: The role of perfectionism as a correlate of perinatal depressive symptomatology, and as a predictor of postpartum depressive disorder was examined. Methods: 386 women in their third trimester of pregnancy (mean age = 30.08 years; SD = 4.205; range = 19–44) completed the Portuguese versions of Multidimensional Perfectionism Scale, Beck Depression Inventory-II/BDI-II, Postpartum Depression Screening Scale/PDSS and three additional questions evaluating anxiety trait, life stress perception and social support. Diagnoses of depression (ICD-10/DSM-IV) were obtained using the Portuguese version of the Diagnostic Interview for Genetic Studies/OPCRIT system. Women who were clinically depressed in pregnancy (ICD-10/DSM-IV) were excluded from the analysis. Results: Self-Oriented Perfectionism/SOP and Socially Prescribed Perfectionism/SPP subcomponents were significant correlates of depressive symptomatology (BDI-II/PDSS) in pregnancy. SPP-Others High Standards/OHS was a significant predictor of postpartum depressive symptomatology (BDI-II/PDSS), and SPP-Conditional Acceptance/CA was a predictor of postpartum depressive symptomatology (PDSS). None of the perfectionism subscales predicted postpartum depressive disorder (ICD-10/DSM-IV). Conclusions:SOP and SPP have shown to be relevant correlates of depressive symptomatology in pregnancy. In the present study, SPP-OHS and SPP-CA were also significant correlates of perinatal depressive symptomatology, as well as important risk factors for depressive symptomatology in postpartum. Perfectionism subscales were not significant predictors of postpartum depressive disorder (ICD-10/DSM-IV). While SPP maladaptive influence was supported, SOP was shown to be more heterogeneous in its consequences. These findings may have important implications both for clinical practice and for research.

10.	Nogueira, V.; Bos, S.C.; Valente, J.; Soares, M.J.; Pereira, A.T.; Maia, B.R.; Marques, M.; Gomes, A.A.; Macedo, A.; Azevedo, M.H.. 2011. "Suicidal behaviour in Bipolar Disorder", Trabalho apresentado em 19th European Congress of Psychiatry., In Suicidal behaviour in Bipolar Disorder., Vienna.

11.	Marques, M.; Macedo, A.; Bos, S.C.; Maia, B.R.; Pereira, A.T.; Soares, M.J.; Azevedo, M.H.. 2011. "Mother´s Personality and Infant temperament", Trabalho apresentado em 14th International Congress of ESCAP–European Society for Child and Adolescent Psychiatry, In European Child Adolescent Psychiatry, Finlândia, Helsínquia. Aims: We examined if perfectionism and the perception of being anxious were associated with more negative mother’s infant temperament ratings. Methods: 386 women in their last trimester of pregnancy completed the Multidimensional Perfectionism Scale (MPS), the Beck Depression Inventory-II (BDI-II) and an item about their perception of being anxious. The Portuguese version of the Diagnostic Interview for Genetic Studies and the Operational Criteria Checklist for Psychotic Illness were used to generate diagnoses (DSM-IV/ICD-10). After delivery, women completed the Difficult Infant Temperament Questionnaire (DITQ) and the BDI-II and were interviewed with the DIGS. Women with depression and probable cases (cut-offs adjusted to Portuguese prevalence/BDI-II), were excluded. Results: The DITQ has factorial validity and internal consistency. Perfectionism total scale score and item 6/DITQ (‘‘is your baby irritable or fussy?) were positively correlated. Self Oriented Perfectionism (SOP) in pregnancy and the same item were negatively correlated. Women with low SOP differed from those with medium and high SOP in the total DITQ score. The low SOP group differed from the medium group on items 3 and 4 scores. There were no significant associations with Socially Prescribed Perfectionism. There was an association between anxiety trait status and scoring low, medium or high in the DITQ. SOP (low vs. medium/high) showed to be a significant predictor of total DITQ score and item 3 and 4 scores but trait anxiety as not a predictor total DITQ score. Conclusions: Higher levels of adaptive perfectionism (SOP) are associated (and predict) with a less negative view of infant’s temperament. Some positive perfectionism features could be used to enhance women’s self-efficacy/parental competence and positive affect towards the infants. Antenatal interventions to minimise anxiety can help optimize infant temperament outcomes, leading to maternal and infant mental health better outcomes.

12.	Maia, B.R.; Pereira, A.T.; Marques, M.; Soares, M.J.; Bos, S.C.; Valente, J.; Gomes, A.A.; Nogueira, V.; Azevedo, M.H.; Macedo, A.. 2011. "The Role of Perfectionism in Perinatal Depression (ICD-10, DSM-IV and BDI-II, PDSS)", Trabalho apresentado em 19th European Congress of Psychiatry, In European Psychiatry, 26 (Suppl. 1 P03-509) 10.1016/S0924-9338(11)73383-1. , Vienna, Austria. Aims: The role of perfectionism as a correlate of perinatal depressive symptomatology, and as a predictor of postpartum depressive disorder was examined. Methods: 386 women in their third trimester of pregnancy (mean age = 30.08 years; SD = 4.205; range = 19–44) completed the Portuguese versions of Multidimensional Perfectionism Scale, Beck Depression Inventory-II/BDI-II, Postpartum Depression Screening Scale/PDSS and three additional questions evaluating anxiety trait, life stress perception and social support. Diagnoses of depression (ICD-10/DSM-IV) were obtained using the Portuguese version of the Diagnostic Interview for Genetic Studies/OPCRIT system. Women who were clinically depressed in pregnancy (ICD-10/DSM-IV) were excluded from the analysis. Results: Self-Oriented Perfectionism/SOP and Socially Prescribed Perfectionism/SPP subcomponents were significant correlates of depressive symptomatology (BDI-II/PDSS) in pregnancy. SPP-Others High Standards/OHS was a significant predictor of postpartum depressive symptomatology (BDI-II/PDSS), and SPP-Conditional Acceptance/CA was a predictor of postpartum depressive symptomatology (PDSS). None of the perfectionism subscales predicted postpartum depressive disorder (ICD-10/DSM-IV). Conclusions: SOP and SPP have shown to be relevant correlates of depressive symptomatology in pregnancy. In the present study, SPP-OHS and SPP-CA were also significant correlates of perinatal depressive symptomatology, as well as important risk factors for depressive symptomatology in postpartum. Perfectionism subscales were not significant predictors of postpartum depressive disorder (ICD-10/DSM-IV). While SPP maladaptive influence was supported, SOP was shown to be more heterogeneous in its consequences. These findings may have important implications both for clinical practice and for research.

13.	Gomes, A.A.; Tavares, J.; Bos, S.C.; Soares, M.J.; Murta, J.P.; Marques, M.; Maia, B.R.; Pereira, A.T.; Valente, J.; Cabral, A.S.; Macedo, A.; Azevedo, M.H.. 2010. "Sleep, well-being, lifestyle, and academic variables: which are the main predictors of academic achievement at university?", Trabalho apresentado em 20th Congress of the European Sleep Research Society, In Journal of Sleep Research, Lisboa, Portugal. Objective: To examine whether sleep variables would emerge as significant predictors of academic performance at university, when other potential predictors (such as class attendance; time devoted to study; substance use) are considered. Methods: A sample of 1654 (55% F) full time students of a public Portuguese University, aged 17–25 yr (M = 19.98 ± 1.65), attending 18 undergraduate degrees (1st-3rd curricular years), answered to a selfresponse questionnaire covering demographic, sleep, academic, lifestyle and well-being variables, completed at the middle of the semester. As a measure of academic achievement, a final mark for each student was collected at the end of the semester, and raw scores were converted into standardized z scores. As to data analysis, the main predictors of end of semester marks were identified through a multiple regression analysis: [1] firstly, a correlation matrix was examined to select the potential predictors and prevent multicollinearity; [2] secondly, a stepwise regression analysis was conducted, entering as potential predictors only those variables showing significant associations with marks. Results: From fifteen variables included in the model as potential predictors (Age, Previous Academic Achievement, Vocational Preferences, Class Attendance, Study Time, Cognitive Functioning, Night Outings, Coffee, Tobacco, Alcohol and Other Substances consumption, Sleep Quality, Enough Sleep, Sleep Phase, Sleep-Wake Cycle Irregularity), five were shown to be significant predictors of marks: Previous Academic Achievement; Class Attendance; Enough Sleep; Night Outings; and Sleep Quality, R-squared = .14, adjusted Rsquared = .14, F (5,1234) = 40.99, P < .0001. Associations of the remainder sleep, academic, well-being, and lifestyle variables (e.g., time devoted to study; alcohol consumption), with academic achievement, lost significance in stepwise regression. Conclusion: Together with class attendance, (...).

14.	Bos, S.C.; Soares, M.J.; Marques, M.; Maia, B.R.; Pereira, A.T.; Gomes, A.A.; Macedo, A.; Azevedo, M.H.. 2010. "Can disordered eating attitudes predict sleep disturbance overtime? ", Trabalho apresentado em 20th Congress of the European Sleep Research Society, In Journal of Sleep Research, Lisboa, Portugal. Objective: To explore whether disordered eating attitudes predicted sleep disturbances overtime. Methods: A total of 870 university students took part of the study, 592 participated one year later (T1) and 305 students two years later (T2). The Eating Attitudes Test-40 (EAT-40) was used to assess global disordered eating attitudes/behaviours (EAT total score), Diet Concerns, (DC), Bulimic Behaviours (BB) and Social Pressure to Eat (SPE). Sleep disturbances were assessed with two items related to difficulties initiating sleep (DIS) and difficulties maintaining sleep (DMS). A sleep disturbance index (SDI) was calculated by summing DIS and DMS scores. Results: The group of subjects with more disordered eating attitudes, BB and SPE scores at baseline experienced more sleep disturbances (DIS, DMS and SDI) at T1 and T2 than the group with less abnormal eating attitudes. In addition, baseline EAT total scores, BB and SPE scores were higher within the groups who experienced onset insomnia, remission insomnia and persistent insomnia overtime comparatively to the good sleepers group. Global disordered eating attitudes/behaviours at baseline predicted DIS (T1: 6.2%, P < .001; T2: 4.5%, P = .006), DMS (T1: 4.1%, P < .001; T2: 4.2%, P = .024) and SDI (T1: 6.8%, P < .001; T2: 5.5%, P < .001) at T1 and T2. Students with increased BB and SPE scores at baseline were more likely to experience onset and persistent insomnia in the long term. Conclusions: The present results indicate that assessing disordered eating attitudes in university students, particularly BB and SPE, might be helpful preventing subsequent sleep disturbances which are known to affect negatively human’s health and well-being.

15.	Azevedo, M.H.; Maia, B.R.; Marques, M.; Bos, S.C.; Nogueira, V.; Soares, M.J.; Pereira, A.T.; Gomes, A.A.; Valente, J.; Macedo, A.. 2010. "Psychometric properties of the Portuguese version of the Pre Sleep Arousal Scale", Trabalho apresentado em 20th Congress of the European Sleep Research Society, In Journal of Sleep Research, Lisboa, Portugal. Objective: To translate and to analyse the reliability and validity of the Pre-Sleep Arousal Scale (PSAS). Methods: The survey contained the PSAS and measures of mood (POMS subscales: depression, anger-tension, and vigour-friendliness), neuroticism (NEO-PI-R) and sleep habits/difficulties (sleep duration, depth, quality, latency, nighttime awakenings, time to get up in the morning, and sleeplessness). 321 university students (256 females, 79.6%), mean age 20.39 years (SD=1.79; range = 17–25) participated in the study. Results: Based on the scree test of Catell a 2-factor solution was found. Eight items loaded in a Somatic component and 8 items loaded in a Cognitive component. The PSAS test-retest correlation was of .80. Somatic and Cognitive Cronbach alphas were of .86 and .85, respectively. Significantly moderate correlations were found between Somatic and Cognitive subscales and depression and anger/anxiety. Vigour/friendliness was significantly and negatively correlated with the Somatic subscale. Significantly, albeit small, correlations were found between PSAS subscales and neuroticism subscales of anxiety, hostility and depression. Impulsivity was correlated with Cognitive arousal. Significantly positive and moderate correlations were found between PSAS subscales and light sleep, poor sleep, nighttime awakenings and sleeplessness. Sleep duration was negatively, but significantly, correlated with both subscales. In general, stronger correlations were found with Cognitive arousal. A Mann-Whitney U Test was conducted to explore the impact of Somatic and Cognitive levels of arousal on sleep quality. Significant differences were found between poor and good sleepers, with effect sizes being higher for the Cognitive subscale. Conclusions: The reliability and validity analysis of the Portuguese version of the PSAS showed to be very good. Somatic and Cognitive arousal correlated with measures of negative mood states, neuroticism, and all sleep variables. (...).

16.	Marques, M.; Bos, S.C.; Soares, M.J.; Maia, B.R.; Pereira, A.T.; Valente, J.; Gomes, A.A.; Macedo, A.; Azevedo, M.H.. 2010. "Is insomnia in pregnancy a risk factor for postpartum depression?", Trabalho apresentado em 20th Congress of the European Sleep Research Society, In Journal of Sleep Research, Lisboa, Portugal. Aim: Investigate if insomnia in late pregnancy is a risk factor for postpartum depressive symptomatology/postpartum depression (PPD), following both a dimensional and a categorial approach. Methods: 581 women (mean age = 29.8; standard deviation = 4.53) in their last trimester of pregnancy answered questions/questionnaires about lifetime history of insomnia, current sleep perception, current mood and depressive symptomatology. They were interviewed with the Portuguese Diagnostic Interview for Genetic Studies. After delivery 382 (65.7%) mothers participated again in the study. Results: Negative Affect (NA) was a significant predictor of postpartum depressive symptomatology (15.2% of the total variance explained) and women with higher NA were 4.6 times (CI 95% = 1.69–12.74) and 5.3 times (CI95% = 2.26–12.58) more likely of experiencing PPD (Diagnostic and Statistical Manual-4th edition; DSM-IV/International Classification of Diseases-10th edition; ICD- 10, respectively) than women with lower values of NA. Lifetime depression was a significant predictor of postpartum depressive symptomatology and of ICD-10/PPD diagnoses (OR = 2.6; CI95% = 1.16–4.38). Positive Affect (PA) showed to be an important protective factor for postpartum depressive symptomatology and DSM-IV/PPD (OR = ).94; CI95% = 1.20–2.33). Insomnia in pregnancy was not per se a risk factor for PPD caseness (PPD/DSM-IV or PPD/ICD-10) but it was a significant predictor of postpartum depressive symptomatology. Controlling NA, PA and lifetime depression, insomnia lost its predictive role, suggesting that these variables may act as mediators. Conclusions: Associations between insomnia, NA, PA and lifetime depression should be assessed in pregnancy. This might help to preventively target NA, enhance PA and reduce the likelihood of experiencing postpartum depressive symptomatology.

17.	Quintal, J.; Marques, M.; Soares, M.J.; Rosmaninho, J.; Lopes, M.; Maia, B.R.; Pereira, A.T.; Macedo, A.; Gomes, A.A.; Bos, S.C.; Azevedo, M.H.. 2010. "Neuroticism, coping styles and sleep quality in female students", Trabalho apresentado em 20th Congress of the European Sleep Research Society, In Journal of Sleep Research, Lisboa, Portugal. Objectives: Studies have shown a strong association between neuroticism and sleep disruption/quality. However, few studies have considered the influence of coping styles, as suppression, in sleep quality, particularly in females, the gender which presents poorer sleep quality. Our aim was to study the possible associations between neuroticism, coping styles (suppression/reappraisal) and several sleep variables, in a female student sample. Methods: 303 female students (mean age = 18.8 years; SD = 1.13; range = 17–24) from the Medicine course of Coimbra University completed the subscales Extraversion and Neuroticism from the Eysenck Personality Inventory (EPI) and the Emotion Regulation Questionnaire (ERQ), which evaluates expressive suppression and cognitive reappraisal. They also answered several items about their sleep duration, depth, quality, needs, flexibility, latency, nighttime awakenings, time to get up in the morning and sleeplessness. Results: Neuroticism was strongly correlated with poor sleep (rho =.193; P < .01) and sleep needs (rho = .217; P < .01). Both suppression and reappraisal were not associated with sleep variables. Conclusions: Neuroticism was associated with poorer sleep quality in our sample. Contrary to our expectations, coping styles did not influence sleep.

18.	Lopes, M.; Rosmaninho, J.; Quintal, J.; Soares, M.J.; Maia, B.R.; Marques, M.; Pereira, A.T.; Gomes, A.A.; Bos, S.C.; Macedo, A.; Azevedo, M.H.. 2010. "Sleep duration and BMI in university students.", Trabalho apresentado em 20th Congress of the European Sleep Research Society, In Journal of Sleep Research, Lisboa, Portugal. Objectives: The aim of this study was to analyse the association between body mass index (BMI) and sleep duration (SD), sleep needs (SN), sleep deficit, physical and psychological health in Portuguese medical students of both genders. Methods: Four hundred and sixty-five participants (303 females; 65.2%); with a mean age of 18.77 (SD = 1.18, range 17–26) completed a questionnaire administered during classes regarding self-reported height, weight, SD, SN, physical and psychological health. BMI was calculated as weight (Kg) divided by the square of height (m). BMI groups were constructed using World Health Organization criteria. Sleep deficit was determined by subtracting sleep needs from sleep duration. Results: Females reported significantly higher subjective sleep needs (7.8 hours versus 8.1 h; P = .014), lower BMI (md = 20.55; md = 22.20, P = .001) and lower psychological health (P < .001) compared to males. There were no significant associations between sleep duration and BMI both in total sample (r = ).068, P = .148) and in the female (r = ).003; P = .955) and male subsamples (r = ).117; P = .141); therefore the analysis on this association were performed for the global sample. No significant associations were also found between BMI and sleep duration when subjects were divided by BMI groups (P = .351). Moreover, significant associations were observed between BMI and sleep needs (r = ).122; P < .01) and physical health (r = ).137; P < .01). Conclusion: In Portuguese medical students BMI was not significantly associated with sleep duration, sleep deficit and psychological health but it was negatively associated with physical health and sleep needs.

19.	Bos, S.C.; Marques, M.; Pereira, A.T.; Maia, B.R.; Soares, M.J.; Valente, J.; Gomes, A.A.; Macedo, A.; Azevedo, M.H.. 2009. "The rest-activity cycle and symptoms of depression in motherhood.", Trabalho apresentado em 3º Congresso Internacional de Medicina de Sono, In Sleep Medicine, São Paulo. Objective: To explore associations between disrupted rest-activity cycles and symptoms of depression in the perinatal period. Methods: Mothers were evaluated in the third trimester of pregnancy (n=61), at 3 months postpartum (n=33), at 6 months postpartum (n=21) and at 12 months postpartum (n=8). Twenty-one non-pregnant women were used as a reference group. Self-reported inventories (Beck Depression Inventory, BDI-II; Postpartum Depression Screening Scale, PDSS) were completed to assess depressive symptoms and actigraphy was used to measure rest-activity patterns. Correlation analyses between BDI-II and PDSS total scores and rest-activity parameters within the same subjects were calculated. Results: The rest-activity cycle of mothers was disturbed in pregnancy and particularly during the first months after delivery. Symptoms of depression were associated with altered rest-activity cycles, with a less marked dichotomy between sleep and wake states (BDI-II, r= -0.28, p=0.03), with less activity when awake (from r= -0.26, p=0.05, PDSS to r= -0.31, p=0.02, BDI-II) or before retiring (BDI-II, r= -0.40, p<0.01) and particularly with more inactivity in the hours after rising (BDI-II, r=0.28, p=0.03; PDSS, r=0.33, p=0.01). Conclusion: Engaging in daily activities when awake and a good sleep hygiene could eventually ameliorate mood decrements in mothers-to-be or mothers who have recently given birth.

20.	Soares, M.J.; Bos, S.C.; Maia, B.R.; Pereira, A.T.; Marques, M.; Valente, J.; Gomes, A.A.; Macedo, A.; Azevedo, M.H.. 2009. "Body Mass Índex, Eating Attitudes and Sleep Disturbances in Young Adults", Trabalho apresentado em 3º Congresso Internacional de Medicina de Sono, In Sleep Medicine, São Paulo.

21.	Pereira, A.T.; Bos, S.C.; Soares, M.J.; Gomes, A.A.; Valente, J.; Macedo, A.; Marques, M.; Maia, B.R.; Azevedo, M.H.. 2008. "The BDI-II factor structure in pregnancy and postpartum: Two or three Factors?", Trabalho apresentado em 6th International Congress of Cognitive Psychotherapy, In Psychomed-Rivista quadrimestrale di psicoterapia, medicina psicosociale, psicologia della salute e preventiva, Roma. The purpose of the present study was to investigate the factor structure of the Beck Depression Inventory II (BDI-II) in pregnancy and postpartum. 331 pregnant women with a mean age of 29.7 years (SD=4.6; Range=19-42 years) who were in their last trimester of pregnancy (M=32.7, SD=3.4, Range=26-41 weeks of gestation) answered the BDI-II. Most women, 65.6%, were nulliparas. At approximately 3 months after partum 354 mothers aged 30.6 years (SD=4.6; Range=18-44 years), mostly primiparas (57.4%), also filled in the BDI-II. Data were analysed using factor analyses with principal components solution and varimax rotation. Based on the scree test of Catell a 2-factor solution and a 3-factor solution were explored in pregnancy and postpartum. The 2-factor solution was identical in pregnancy and postpartum. The items loading in the Cognitive-affective factor and in the Somatic-anxiety factor were the same. An exception was the «indecisiveness» item which loaded on the Cognitive-affective dimension in pregnancy whereas in postpartum loaded in the Somatic-anxiety factor. Another difference was that the Cognitive-affective factor was the factor explaining more of the BDI-II total variance in pregnancy whereas in postpartum was the Somatic-anxiety factor. The 3 factor solution of the BDI-II in pregnancy and postpartum slightly diverged. Besides the Cognitive-affective and the Somatic-anxiety factors, a third factor, Fatigue, was obtained in pregnancy while Guilt was the third factor identified in postpartum. This study reveals that the 3-factor solution of the BDI-II in pregnancy and postpartum might be more appropriate to assess depressive symptomatology in these specific periods of time.

22.	Marques, M.; Macedo, A.; Soares, M.J.; Maia, B.R.; Pereira, A.T.; Bos, S.C.; Gomes, A.A.; Valente, J.; Azevedo, M.H.. 2008. "Can we talk about “Premedical Syndrome” among Portuguese Medical students?", Trabalho apresentado em 6th International Congress of Cognitive Psychotherapy, In Psychomed-Rivista quadrimestrale di psicoterapia, medicina psicosociale, psicologia della salute e preventiva, Roma. In Portugal, the Medical school selection process relies exclusively on past academic results, involving the most stringent criteria of all courses, with no attention given to the personality traits of the students. In a competitive context, perfectionism dimensions may be relevant to consider. Socially Prescribed Perfectionism (SPP) has been correlated with Neuroticism, while Self-Oriented Perfectionism (SOP) is strongly associated with Conscientiousness. These domains of personality have been linked (lower levels of Neuroticism and higher levels of Conscientiousness) to academic and professional success in Medicine. The premedical syndrome describes premedical students as overachieving, excessively competitive, cynical, dehumanized, overspecialized and narrow. AIM: To compare SPP and SOP levels between Medical and Humanities students, as they may be possible indicators of the premedical syndrome among Portuguese medical students. METHODS: The Portuguese version of the Multidimensional Perfectionism Scale was administered to 908 undergraduate students from Medicine and Humanities courses of Coimbra University. The sample covered students from the 1st to the 5th year of the courses but most of the students were from the 1st year (n = 436). RESULTS: With respect to SPP, significant statistical differences were found, with Medicine students showing lower levels (mean 48.60 ± 11.02; p=.023) than Humanities students (mean 50.00 ± 9.56). No significant differences were found in SOP. CONCLUSION: Our results are reassuring, suggesting the lack of a negative impact of the medical school selection process in the personality traits of the students and the probable absence of the premedical syndrome.

23.	Maia, B.R.; Bos, S.C.; Macedo, A.; Soares, M.J.; Marques, M.; Pereira, A.T.; Gomes, A.A.; Valente, J.; Azevedo, M.H.. 2008. "The Portuguese Multidimensional Perfectionism Scale Factor Structure in Pregnant Women.", Trabalho apresentado em 6th International Congress of Cognitive Psychotherapy, In Psychomed-Rivista quadrimestrale di psicoterapia, medicina psicosociale, psicologia della salute e preventiva, Roma. Aim: Explore the factor structure of the Portuguese Multidimensional Perfectionism Scale (MPS) in pregnant women. Methods: The sample comprises 421 women (M=29.8, SD=4.48; Range=19-44 years) in their last trimester of pregnancy (M=32.6, SD=3.39, Range=25-41 weeks of gestation); 64.4% were nulliparous. To assess perfectionism the Portuguese version of the MPS (Hewitt & Flett, 1991; Soares, Gomes, Macedo, Santos & Azevedo, 2003), 32-item self-report scale was used. A factor analysis was performed using the principal components solution with varimax rotation. Results: Based on the scree test of Cattell two factor structures were considered. The first structure was composed by 2 factors explaining 37.4% of the total variance. Factor 1 - Self-Oriented Perfectionism (SOP), included items such as “I am perfectionist in setting my goals”. Factor 2 - Socially Prescribed Perfectionism (SPP), included items such as “My family expects me to be perfect”. The second structure revealed 3 factors. Factor 1, SOP, was very similar to the one obtained in the two factors solution. However, SPP was divided in two factors, with distinct types of self-beliefs: Factor 2 – Others’ High Standards, which reflects the belief that others hold high standards or expectations for the self and Factor 3 - Conditional Acceptance, which reflects the believe that being loved and accepted by others is contingent on high achievement. The 3 factors explained 42.9% of the total variance. Conclusion: In Portuguese pregnant women the SOP factor of the MPS is robust. However, we believe that to assess the negative consequences of SPP a 3 factor solution of the MPS seems more appropriate, in the sense that “Conditional Acceptance” may be the SPP component more strongly associated with several psychopathological outcomes (Campbell & DiPaula, 2002).

24.	Azevedo, M.H.; Bos, S.C.; Pereira, A.T.; Maia, B.R.; Marques, M.; Soares, M.J.; Gomes, A.A.; Valente, J.; Macedo, A.. 2008. "Psychological Distress in Pregnant women with Insomnia.", Trabalho apresentado em 22nd Annual Meeting of the Associated Professional Sleep Societies, In Sleep, Baltimore, Maryland.

25.	Bos, S.C.; Marques, M.; Pereira, A.T.; Soares, M.J.; Macedo, A.; Azevedo, M.H.. 2008. "Are three 24-hour consecutive days of actigraphic recording sufficient to assess the rest-activity rhythm changes associated with pregnancy and postpartum? –Preliminary results", Trabalho apresentado em 22nd Annual Meeting of the Associated Professional Sleep Societies, In Sleep, Baltimore, Maryland.

26.	Macedo, A.; Maia, B.R.; Soares, M.J.; Pereira, A.T.; Bos, S.C.; Marques, M.; Cabral, A.S.; Valente, J.; Pocinho, F.; Pato, M.T.; Azevedo, M.H.. 2008. "Obsessive Compulsive-Related Disorders and Perfectionism: A study in a Portuguese population", Trabalho apresentado em XIV World Congress of Psychiatry, Praga, República Checa (20-25 Setembro). , In Journal of Czech and Slovak Psychiatry , Praga, República Checa.

27.	Azevedo, M.H.; Bos, S.C.; Soares, M.J.; Pereira, A.T.; Marques, M.; Maia, B.R.; Gomes, A.A.; Macedo, A.. 2008. "Perfectionism and sleep disturbance: a longitudinal study", Trabalho apresentado em 19th Congress of the European Sleep Research Society (ESRS), In Journal of Sleep Research, Glasgow, Reino Unido. Aim: To examine whether perfectionists predict self-reported sleep disturbances over time. Methods: The Hewitt and Flett Multidimensional Perfectionism Scale (1991) was used to measure total perfectionism, self-oriented perfectionism (SOP), socially-prescribed perfectionism (SPP) and other-oriented perfectionism (OOP). Sleep disturbance was assessed with two items: (1) I have difficulty in falling asleep and (2) I wake up many times during the night. Out of 870 students who completed those measures at baseline, 592 and 305 completed the same measures one year (T1) and two years later (T2) respectively Results: Subjects who reported insomnia (had difficulties initiating sleep/maintaining sleep often/very often and always) at baseline, T1 and T2 (persistent insomnia) had significantly higher scores of baseline SPP (T1 M551.5, SD515.8; T2 M555.0; SD519.0) than subjects that in all stages of the study reported that never/rarely had sleep problems (good sleepers group) (T1 M541.9, SD511.4; T2 M542.2, SD512.3, Po0.001 in both cases). Regression analyses showed that baseline SPP at T1 and T2 was the only significant positive predictor of difficulties in falling asleep (T1 partial R50.187; T2 partial R50.196, Po0.001) and difficulties maintaining sleep (T1 partial R50.116; T2 partial R50.244, Po0.001). Conclusion: A new finding is that SPP was found to be the most reliable predictor of sleep disturbances over time.

28.	Azevedo, M.H.; Bos, S.C.; Maia, B.R.; Pereira, A.T.; Marques, M.; Soares, M.J.; Valente, J.; Macedo, A.. 2007. "Sleep disturbances in late pregancy.", Trabalho apresentado em World Association of Sleep Medicine Second World Congress, In Sleep Medicine, Bangkok.

29.	Pereira, A.T.; Maia, B.R.; Bos, S.C.; Marques, M.; Valente, J.; Gomes, A.A.; Macedo, A.; Azevedo, M.H.. 2006. "Perceived Stress and Insomnia in late Pregnancy - Preliminary report", Trabalho apresentado em 18th Congress of the European Sleep Research Society, In Perceived Stress and Insomnia in late Pregnancy - Preliminary report, Innsbruck. Aim: To investigate the association between the perception of stress and self-reported insomnia in the last trimester of pregnancy. Methods: The data for this study were drawn from an ongoing cohort prospective study on Sleep and Postpartum Depression. To assess Insomnia six items were applied: three for insomnia symptoms and three to measure interference with activities and daytime consequences. Overall perception of life stress was measured using the following item: How stressful is your life at the present time? (scored from 1 = Not stressful at all to 4 = Very stressful). Results: To date 60 women (mean = 30.5 ± 4.8 years) were evaluated during their last trimester of pregnancy (mean=32.4 ± 3.7 weeks). Based on sleep item responses two groups were formed: group 1 without insomnia (n = 33); and group 2 with insomnia (n = 27). Compared to the group without insomnia women with insomnia reported significantly more stress (Mann–Whitney U-test = 271.500; P value = 0.010). Conclusion: In this small sample of pregnant women perceived life stress was associated with insomnia.

30.	Azevedo, M.H.; Soares, M.J.; Maia, B.R.; Pereira, A.T.; Gomes, A.A.; Bos, S.C.; Cabral, A.S.; Macedo, A.. 2006. "Perfectionism and Sleep Disturbance in Young Males.", Trabalho apresentado em 18th Congress of the European Sleep Research Society, In Perfectionism and Sleep Disturbance in Young Males, Innsbruck.

31.	Bos, S.C.; Pereira, A.T.; Maia, B.R.; Marques, M.; Soares, M.J.; Cabral, A.S.; Macedo, A.; Azevedo, M.H.. 2006. "Self reported Insomnia and Mood States in Late Pregnancy - Preliminary report", Trabalho apresentado em 18th Congress of the European Sleep Research Society, In Self reported Insomnia and Mood States in Late Pregnancy - Preliminary report, Innsbruck. Aim: To investigate the association between self reported insomnia and mood states in the last trimester of pregnancy. Methods: The data for this study were drawn from an ongoing cohort prospective study on Insomnia and Postpartum Depression*. To assess insomnia 6 items were applied: 3 items to evaluate insomnia symptoms and 3 items to measure insomnia daytime consequences. Mood states were assessed using the Portuguese version (Azevedo et al. 1991) of the Profile of Mood States (POMS; McNair et al., 1971) a 65- adjective Likert scale which evaluates 6 mood dimensions: Tension, Depression, Anger, Fatigue, Confusion and Vigour. Insomnia and mood states were self-reported considering the previous month. To date 60 women (mean=30.5 ± 4.8 years) were evaluated during their last trimester of pregnancy (mean=32.4 ± 3.7 weeks). Based on sleep item responses 3 groups were formed: a group with insomnia (women who referred symptoms of insomnia and daytime impairment; n = 27); a group with insomnia symptoms (n = 15) and a control group without insomnia complaints (n = 18). Mann–Whitney statistical tests were applied to compare group differences in POMS sub-scales scores. Results: The insomnia group revealed increased Tension, Depression, Anger, Fatigue, Confusion and decreased Vigour compared with both the control group (p values ranged from 0.024 for Anger to < 0.001 for Vigour) and the group with insomnia symptoms (P values ranged from 0.018 for Vigour and 0.006 for Depression). Significant differences were not observed between the group with insomnia symptoms and the control group (P > 0.05) in all POMS scales. Conclusion: Self reported insomnia in pregnant women was found to be associated with negative mood.

32.	Ruano, D.; Aulchenko, Y.S.; Macedo, A.; Soares, M.J.; Cabral, A.S.; Valente, J.; Azevedo, M.H.; Hutz, M.H.; Gama, C.G.; Lobato, M.I.; Belmonte-de-Abreu, P.; Van Belzen, M; Heutink, P.; Pato, C.N.; Palha, J.A.. 2005. "Association between the Neurogranin gene and schizophrenia in males.", Trabalho apresentado em XIIIth World Congress of Psychiatric Genetics, In American Journal of Medical Genetics (Neuropsychiatric Genetics), Boston, E.U.A.. Introduction: The Neurogranin (NRGN) gene produces a postsynaptic brain-specific protein that regulates calmodulin/Ca2þ availability in neurons [1]. It is therefore involved in the NMDA-receptor mediated cascade, proposed to be altered in schizophrenia. NRGN expression is regulated by thyroid hormones and retinoids, which modulate the expression of various genes suggested to be implicated in schizophrenia. In addition, the NRGN gene is located at chromosome 11q24, a significant susceptibility locus in schizophrenia linkage studies [2]. Methods: We performed an association study in a Portuguese sample composed of 244 schizophrenic patients and 210 mentally healthy controls, in an independent sample composed of 73 trios from the Azores, and in a very small sample of Brazilian schizophrenic males. Results: Genotype and haplotype analysis showed association between NRGN and schizophrenia in Portuguese males. This association was confirmed by the analysis of the Azorean sample. Conclusions: Our results provide evidence that the NRGN gene is involved in the etiology of schizophrenia in Portuguese males. References: 1. Huang KP et al (2004) Neurogranin/RC3 enhances long-term potentiation and learning by promoting calcium-mediated signaling. J.Neurosci. 24 (47):10660–10669. 2. Gurling HMet al (2001) Genomewide genetic linkage analysis confirms the presence of susceptibility loci for schizophrenia, on chromosomes 1q32.2, 5q33.2,and 8p21-22 and provides support for linkage to schizophrenia, on chromosomes 11q23.3-24 and 20q12.1-11.23. Am.J.Hum.Genet. 68 (3):661–673.

33.	Pereira, A.T.; Bos, S.C.; Maia, B.R.; Soares, M.J.; Cabral, A.S.; Macedo, A.; Azevedo, M.H.. 2005. "The Portuguese short form of the Eating Attitudes Test-40", Trabalho apresentado em XXXV Annual Congress of the European Association for Behavioural and Cognitive Therapies, In Abstract Book, Salónica, Grécia. To develop a Portuguese short form, the Eating Attitudes Test-40 (EAT-40) was administered to a community sample of 922 female students and to a clinical sample of 63 females suffering from an eating disorder. With the EAT responses of the community sample a factor analysis was performed and items with factor loadings > or = 0.30 were selected. Internal consistency was computed for both the instrument and the factors. To study the discriminant capacity the proportion of symptomatic answers and the mean scores were compared between the clinical (N = 63) and control (N = 63) samples. Three factors were extracted: Drive for Thinness (14 items, alpha = .839), Bulimic Behaviours (8 items, alpha = .670), Social Pressure to Eat (3 items, alpha = .758). The short form is composed of 25 items and shows good internal consistency = 0.839. Symptomatic answers for all items (except one) and total mean scores were significantly higher (p < .001) in the clinical sample than in community sample.

34.	Coelho, I.M.; Dourado, A.; Valente, J.; Macedo, A.; Soares, M.J.; Pato, M.T.; Pato, C.N.; Palha, J.A.; Azevedo, M.H.. 2004. "Is age at onset a useful marker for sub-typing bipolar disorder?", Trabalho apresentado em XIIth World Congress of Psychiatric Genetics, In American Journal of Medical Genetics (Neuropsychiatric Genetics), Dublin, Irlanda. To compare two groups of bipolar patients defined by age at onset of illness. Several clinical aspects were analyzed including psychotic features, course, medical/psychiatric comorbidity and female reproductive events. The sample comprises 150 Portuguese bipolar patients (92 females), aged 16–89 years (mean=44.5, SD=15.9), 48.7% were married, 32% single and 18.7% were divorced/separated/widowed. The data for this study were drawn from ongoing research projects on Genetic Analysis of Psychosis. Most of the patients (n=118, 78.7%) had a family history of schizophrenia and/or affective disorder. All were interviewed using the Portuguese version of the Diagnostic Interview for Genetic Studies (DIGS) and diagnoses were based on the OPCRIT Polydiagnostic System (selected according DSM-III-R and/or CID-10 Diagnostic Criteria definitions). The age at onset was defined according to the OPCRIT definition-the earliest age at which medical advice was sought for psychiatric reasons or at which symptoms began to cause subjective distress or impair functioning—(mean=25.05, SD=9.25, range=12–59). Comparing the two groups of patients (age onset<25 years, n=86 vs.=25 years, n=64) no significant differences were found in most of the variables studied: birth/early development abnormal complications, family history of schizophrenia/affective disorder, substance use disorder, co-occurrence of psychotic and affective symptoms, nicotine use, medical and psychiatric comorbidity, suicide attempts, conduct problems, rapid cycling and mixed affective states, course of disorder and female reproductive events. A significant association was found between an earlier age at onset and emotional problems during pregnancy and post-partum. However we found trends of association between lower age of onset and some of the variables above outlined. Our results are not in agreement with those of previous studies relatively to the possibility of considering the age at onset of bipolar disorder as a useful p.

35.	Azevedo, M.H.; Soares, M.J.; Ferreira, A.M.; Gomes, A.A.; Bos, S.C.; Macedo, A.. 2004. "Perfectionism and Sleep Disturbance in Female Students", Trabalho apresentado em 17th Congress of the European Sleep Research Society; Praga, República Checa, 5 a 9 de Outubro de 2004., In Journal of Sleep Research, Praga, República Checa. Aim: To investigate the association between perfectionism and self-reported sleep disturbances in female university students. Method: The data for this report were drawn from an ongoing research project on Perfectionism and Obsessive–Compulsive Spectrum Disorders*. Hewitt and Flett’s [1] Multidimensional Perfectionism Scale (MPS) in its validated Portuguese version, is used to measure self-oriented (SOP), socially prescribed (SPP), and other-oriented (OOP) perfectionism dimensions. A total perfectionism score (MPS Total score) is derived from the sum of scores for the individual items (n = 45). Two sleep items (rated from never = 0 to always = 5) covering difficulties in initiating sleep (DIS) and maintaining sleep (DMS), are used to assess sleep disturbances. An overall index of sleep disturbance (SDI) score is obtained from the sum of scores for each item. Test-retest reliabilities over 4 weeks were: r = 0.637 for DIS; r = 0.588 for DMS, and r = 0.723 for SDI (all P-values = 0.000) Results: The sample comprises 764 females; mean age 19.32 years (SD = 1.54; range = 17–25); 99.1% single. On the basis of the responses to the sleep questions subjects were divided into two groups: (1) Insomniacs (n = 168) consisting of subjects who experienced Difficulties initiating and/or maintaining sleep _Often/Very often and/or Always’, and (2) Good Sleepers (n = 360), including subjects who answered both sleep questions as ’Never and/or Rarely’. Comparing the two groups the Insomniacs had significantly higher mean scores on SPP (47.95 vs. 42.23; t = - 4.871; P = 0.000) and on EMP Total Score (188.72 vs. 180.55; t = ) 3.021; P = .003). No significant differences were found on SOP and OOP. Conclusion: In female university students only socially prescribed perfectionism was associated with sleep disturbances.

36.	Pato, C.N.; Sklar, P.; Kirby, A.N.; Petryshen, T.L.; Medeiros, H.M.; Carvalho, C.; Macedo, A.; Dourado, A.; Coelho, I.M.; Valente, J.; Soares, M.J.; Ferreira, C.P.; Morley, C.P.; Kennedy, J.L.; Azevedo, M.H.; Lander, E.; Daly, M.J.; Pato, M.T.. 2003. "Genome Wide Scan in Portuguese Island Families Identifies Likely Susceptibility Loci for Bipolar Disorder on Chromosomes 6, 11, and 19", Trabalho apresentado em XIth World Congress of Psychiatric Genetics, In American Journal of Medical Genetics , Québec, Canadá. Bipolar disorder is a common psychiatric disorder probably based on complex genetic factors. To understand the genetic basis of this syndrome in Portuguese Island populations, we performed a genome-wide scan of 164 individual from 30 multiplex families with bipolar disorder from the Azores islands (62%), Madeira islands (9%), and Coimbra (29%), a city on the Portuguese mainland. Our genome scan for bipolar disorder revealed 12 chromosomal regions with nominal P-values less than 0.05. The strongest overall finding in bipolar disorder was identified at marker D19S714 (32.44 cM) with an NPL=2.93, P=0.0024. Empirical simulations set a genome-wide threshold of NPL=3.10 for significant linkage. We have begun fine-mapping across additional linkage regions on chromosomes 6 and 11 for bipolar disorder. In both cases we typed an additional 12–16 markers across the original linkage peaks. These linkage signals for bipolar disorder increased, on chromosome 6 at marker D6S1639 (112 cM), with an NPL=3.39, P=0.0002, and on chromosome 11 at marker D11S986 (50 cM), with an NPL=3.38, P=0.0002.

37.	Sklar, P.; Petryshen, T.L.; Pato, M.T.; Kirby, A.N.; Tahl, A.R.; Aldinger, K.A.; Medeiros, H.M.; Macedo, A.; Carvalho, C.; Azevedo, M.H.; Lander, E.; Daly, M.J.; Pato, C.N.. 2003. "Haplotype Mapping of a Complex Disease: Schizophrenia and Chromosome 5q", Trabalho apresentado em XIth World Congress of Psychiatric Genetics, In American Journal of Medical Genetics, Québec, Canadá. We describe the results of an aggressive, haplotype-map based screen to positionally identify a schizophrenia gene on chromosome 5q. Focusing on families of Portuguese descent collected in the Azores, Madeira and the Portuguese mainland, we identified maximum evidence of linkage (NPL=3.1) at marker D5S820. Simulations suggested that this result was at the threshold required to declare significant genome-wide linkage, and when a handful of additional markers were added, the evidence increased to an NPL=3.55. Genotyping a second smaller set of families confirmed linkage to this region. In addition, the same region of 5q was recently identified in a meta-analysis of published genome scans (importantly not including our own study) as containing a highly significant risk factor of global importance. However, as in most complex diseases, the region implicated by linkage is quite large (30 Mb) and two strategies for follow-up were pursued. We selected a set of 15 high likelihood positional and functional candidate genes for initial linkage disequilibrium mapping. SNPs were selected at a density of ~ 1/5kb and genotyped in 98 affected-parent trios and 150 cases and ethnically matched controls. Haplotype maps were constructed across each gene, with individual haplotypes being tested for association with schizophrenia. In the second approach, further fine mapping was undertaken by genotyping an evenly spaced SNP map across the entire 30 Mb region and the data tested for both linkage and association in the original family collection. Data from both of these strategies will be presented and all SNP data is combined to provide a first generation haplotype map of the region.

38.	Macedo, A.; Azevedo, M.H.. 2003. "Perfectionism-Related Disorders: A Latent Phenotype", Trabalho apresentado em 24th International Conference Stress and Anxiety, In Book of Abstracts, Lisboa, Portugal.

39.	Soares, M.J.; Macedo, A.. 2003. "Perfectionism - How to measure it.", Trabalho apresentado em 24th International Conference Stress and Anxiety, In Book of Abstracts, Lisboa, Portugal.

40.	Azevedo, M.H.; Soares, M.J.; Macedo, A.. 2003. "Perfectionism and Eating Attitudes in University Students", Trabalho apresentado em 24th International Conference Stress and Anxiety, In Book of Abstracts, Lisboa, Portugal.

41.	Flores- Villanueva, P; Palha, J.A.; McAlister, C.; Dobesova, L.M.; Belmonte-de-Abreu, P.; Ruano, D.; Macedo, A.; Dourado, A.; Soares, M.J.; Valente, J.; Azevedo, M.H.; Yunis, E.; Faraone, S.V.; Tsuang, M.T.; Goodman, A.B.. 2002. "SNP of Retinoid X Receptor (RXR) at chromosome 6p21.3 associated with schizophrenia", Trabalho apresentado em Xth World Congress of Psychiatric Genetics, In Abstracts for the Xth World Congress of Psychiatric Genetics, Bruxelas, Bélgica. One or another of the three RXR nuclear transcription factors act as master regulators of numerous brain-expressed genes deregulated in the schizophrenic hippocampus. RXRB lies within 1000 kb of NOTCH4. NOTCH4 is strongly associated with schizophrenia in a British sample but not in other samples, suggesting linkage disequilibrium with the causal gene.We have identified an A140T transversion in the 30 end of RXRB with significantly increased frequency among 58 treatment-resistant U. S. Caucasian schizophrenics (fSz) compared to 59 U. S. Caucasian controls (fCt). (fSz¼0.38, fCt¼0.22 P¼0.01), and among 35 African American affected sib pairs compared to 98 African controls (fSz¼0.43, fCt¼0.31 P¼0.03). Allele sharing in the sib pairs is 0.6875. The association is not confirmed in a Caucasian sample from Portugal (Sz¼200, Ct¼80), nor in a Brazilian sample (Sz¼94, Ct¼89) of unknown ethnicity. Since the polymorphism is in the 30 untranslated region of RXRB and does not alter the coding of the gene, it may influence the levels of mRNA transcripts and thus of the protein. Despite inconsistent associations, pathogenic mechanisms in the various populations may be similar, with other mutations in the RXRs affecting either protein levels or functions. RXRB genotype may be useful as a diagnostic marker or predictor of response to treatment. Our data strongly suggest that the retinoid pathway is involved in susceptibility to schizophrenia and that RXRA and RXRG may be candidate genes, as well as RXRB.

42.	Ruano, D.; Macedo, A.; Dourado, A.; Soares, M.J.; Valente, J.; Azevedo, M.H.; Coelho, I.M.; Goodman, A.B.; Palha, J.A.. 2002. "Nur-related receptor 1 and schizophrenia", Trabalho apresentado em Xth World Congress on Psychiatric Genetics, In Abstracts for the Xth World Congress of Psychiatric Genetics, Bruxelas, Bélgica. The human Nur-related receptor 1 (Nurr1) is an orphan nuclear receptor that can be constitutively active as a transcription factor and for which no natural ligand has yet been identified. Nurr 1 heterodimerizes with the retinoic acid 868 Abstracts receptor, RXR, and serves as a partner to facilitate vitamin A (retinoid)-regulated nuclear transcription. In the presence of proper ligands, particularly 9-cis retinoic acid, a final product of the retinoid cascade, the Nurr-1/RXR heterodimer regulates nuclear transcription of target genes. Nurr 1 is a single gene, 8.3 Kb long, consisting of eight exons that maps to chromosome 2q22-23. Several groups have reported evidence supporting a role for Nurr1 in schizophrenia: 1) Nurr1 is expressed predominantly in the dopaminergic neurons in the brain. Studies with Nurr1-null mutant mice demonstrated that Nurr1 is essential for final differentiation of ventral mesencephalic dopaminergic neurons.2) Linkage studies of schizophrenia have implicated the 2q22-23 region.3) Alterations in retinoid metabolism have been suggested to be important in the etiology of schizophrenia.4) Recently, two different missense mutations in the third exon of the Nurr 1 gene have been identified in schizophrenic patients. In the present study we investigated 165 Portuguese patients (104 men, 62 women) and 77 Portuguese controls, both diagnosed in a life-time basis using the Diagnostic Interviewfor Genetic Studies and the OPCRIT system. We failed to detect the described mutations in any of the patients or controls. For all of the above reasons it will be worthwhile to continue to search for other mutations in Nurr-1, which may increase vulnerability to schizophrenia.

43.	Pato, C.N.; Sklar, P.; Daly, M.J.; Verner, A.; Kirby, A.N.; Hudson, T.J.; Medeiros, H.M.; Morley, C.P.; Macedo, A.; Dourado, A.; Coelho, I.M.; Valente, J.; Soares, M.J.; Ferreira, C.P.; Carvalho, C.; Kennedy, J.L.; Azevedo, M.H.; Lander, E.; Pato, M.T.. 2002. "Genome Scan of Schizophrenia, Bipolar Disorder and Psychosis in Portuguese families", Trabalho apresentado em Xth World Congress on Psychiatric Genetics, In American Journal Medcial Genetics (Neuropsychiatrics Genetics, Bruxelas, Bélgica. To identify genes for schizophrenia, bipolar disorder and psychosis, we have performed an initial genome-wide scan on 360 individuals from 67 multiplex Portuguese families mostly from island populations (85%). The island’s recent settlement in the 1500’s may be advantageous. We genotyped 391 markers (10 cM resolution approximately) with an average heterozygosity of 75%. Families were analyzed in three diagnostic categories: schizophrenia (DSM-IV diagnoses of schizophrenia and schiozaffective disorder depressed), bipolar disorder (DSM-IV bipolar disorder or schizoaffective manic) or psychosis (lifetime history of psychotic episode). Multipoint nonparametric linkage analysis using GENEHUNTER software was performed. In the schizophrenia families NPL scores of greater than 1.7 were obtained on chromosomes 1, 5, and 8. The regions on 1 and 5 also had NPL scores greater than 1.8 when all individuals with psychosis were considered regardless of disease phenotype. An additional chromosomal region was identified for psychosis on chromosome 11. In families with bipolar disorder, there were 6 chromosomal regions with NPL scores greater than 2.0 on chromosomes 2, 6, 9, 18, 19 and 20.We are currently fine mapping these regions in an additional 35 families to replicate previous findings and to characterize candidate genes in the region. Our observation of evidence for linkage common to schizophrenia and psychosis may indicate that genes in these regions play a role in both phenotypes, while other evidence for linkage appears to be specific for bipolar disorder and schizophrenia and not the common phenotype psychosis.

44.	Macedo, A.; Moreira, P.; Dourado, A.; Soares, M.J.; Valente, J.; Azevedo, M.H.; Coelho, I.M.; Goodman, A.B.; Saraiva, J.M.; Palha, J.A.. 2002. "Searching for transthyretin polymorphisms in schizophrenia", Trabalho apresentado em 31th Annual Meeting of the Society for Neuroscience, In 2002 Abstract Viewer. Whashington DC: Society for Neursocience, Orlando, E.U.A.. Thyroid hormones (TH) and retinoids are essential for the normal development of the central nervous system. TH and retinoids regulate the expression of several genes, including genes of the neurotransmitter cascades. Transthyretin (TTR) is the major carrier of both TH and vitamin A in the cerebrospinal fluid (CSF). Decreased TTR levels in the CSF of patients with depression and Alzheimer’s disease have been reported, and TTR has been shown to sequester the Alzheimer’s beta-peptide. It is not known whether by itself or through the actions of its ligands TTR might be involved in the pathophysiology of behaviour disorders. The TTR gene, composed of four exons, is localized to chromosome 18q12.1. Positive lod scores at this locus have been reported for schizophrenia and bipolar disorder. In the present study we investigated 143 Portuguese Caucasian patients with schizophrenia, diagnosed in a life-time basis using the Diagnostic Interview for Genetic Studies and the OPCRIT system. We screened, by SSCP analysis, for mutations in the TTR exons 2, 3 and 4. We found 10 patients (7%) carrying the Ser 6 mutation, a polymorphism known to be present in 12% of the normal population. The absence of any other mutation suggests that alterations in the circulating protein are unlikely to be related to schizophrenia. Alterations in the regulatory regions remain as possibilities.

45.	Mundo, E.; Pato, M.T.; Medeiros, H.M.; Carvalho, C.; Ferreira, C.P.; Dourado, A.; Valente, J.; Soares, M.J.; Macedo, A.; Azevedo, M.H.. 2001. "Low prevalence of schizophrenia in a homogeneous Azorean island population.", Trabalho apresentado em IXth World Congress on Psychiatric Genetics, In American Journal Medical Genetics 105:602, 2001, St. Louis, E.U.A.. We report the results of a full ascertainment of subjects with schizophrenia (SCZ) in a homogeneous Azorean island population, collected for genetic analyses and completed in the year 2000. Subjects were identi®ed through psychiatric records and family reports. DSM-IV diagnoses were made with the Diagnostic Interview for Genetic Studies (DIGS). Two hundred and forty patients with SCZ were identi®ed in a base population of 149,000, with an onset time-span of 62 years (1938±2000), and a point prevalence of 0.161. The Lifetime Morbid Risk (LMR) for this population was 0.00166. Further analyses on a sub-sample 189 SCZ patients showed that males had an earlier onset than females (23.78.1 vs 27.59.4, P=0.005). Familial cases (32.8%) had an earlier age at onset than sporadic cases (67.2%) (24.08.5 vs. 26.08.9, P=0.01). In this isolated homogeneous population a much lower prevalence and LMR for SCZ was found but similar patterns in age at onset and gender differences, in comparison to other studies done in island populations. These results suggest that genetic isolation contributed to lower the prevalence of this polygenic disease.

46.	Xu, J.; Pato, M.T.; Torre, C.D.; Leo, R.J.; Medeiros, H.M.; Carvalho, C.; Basile, V.S.; Bauer, A.; Dourado, A.; Valente, J.; Soares, M.J.; Macedo, A.; Ferreira, C.P.; Azevedo, M.H.; Macciardi, F.; Kennedy, J.L.; Pato, C.N.. 2001. "No evidence for linkage disequilibrium between the alpha 7-nicotinic receptor gene locus and bipolar disorder in the Portuguese population.", Trabalho apresentado em IXth World Congress on Psychiatric Genetics, In American Journal Medical Genetics (Neuropsychiatric Genetics), St. Louis, E.U.A.. Recently we reported evidence for linkage disequilibrium and parent-of-origin effect between the alpha 7-nicotinic receptor gene (CHRNA7) locus and schizophrenia in Azorean families. The CHRNA7 is involved in the P50 sensory gating deficits. Freedman et al. had found a positive correlation between the P50 gating deficit in schizophrenia and mania patients. We therefore proceeded to test whether the CHRNA7 genetic linkage extends beyond schizophrenia to include bipolar disorder. We genotyped markers D15S1360, D15S165 and L76630 in 19 bipolar disorder affected Portuguese families with 60 affected individuals and 62 unaffected family members. Linkage analysis by GENEHUNTER did not reveal any significant associations for CHRNA7 in bipolar disorder. D15S1360 results: LOD= -4.93, NPL= 0.15, P= 0.42. D15S165 results: LOD= -15.28, NPL= -0.59, P= 0.76. L76630 results: LOD= -5.11, NPL= -0.091, P= 0.519. Results of ETDT analysis didn't reveal any significant linkage disequilibrium. Marker D15S1360 shows: allele-wise P= 0.14, genotype-wise P= 0.064. Marker D15S165 shows: allele-wise P= 0.62, genotype-wise P= 0.17. Marker L76630 shows: both the allele-wise and the genotype-wise P= 0.41. Analysis of `maternal' and `paternal' meioses has yielded no parent-of-origin effect for three polymorphisms in the entire sample of bipolar disorders. The results suggested no evidence of linkage disequilibrium and parent-of-origin effect between CHRNA7 locus and bipolar disorder in the Portuguese families studied.

47.	Azevedo, M.H.; Clemente, V.; Pissarra, C.M.; Gomes, A.A.; Pereira, A.P.; Silva, E.M.; Macedo, A.. 2001. "Confirmar Autores - Sleep Bruxism and Behavioural disturbance in children: A population-based study", Trabalho apresentado em World Conference Sleep Odyssey 2001: "Physiological Basis for Sleep Medicine", In Actas de Fisiología, Montevideo, Uruguay. AIM. To investigate the relationship between sleep bruxism and behavioural disturbances in Portuguese children attending primary school. METHODS. A sleep-waking questionnaire was sent to the parents of 1381 children attending primary schools in a parish of Coimbra, Portugal. To assess psychiatric symptomatology, the Portuguese version of Rutter’s Children’s Behaviour Questionnaire for completion by teachers was used. A total deviance score is derived from the sum of scores for the individual items (n= 26), an emotional sub-score obtained from the sum of scores of four items (worried, miserable, fearful, tears on arrival at school) and a conduct sub-score obtained from the sum of scores of six items (destructive, fights, disobedient, lies, steals, bullies). The ratings were made by the teachers in the last term of the school year. RESULTS. Of the 988 questionnaires returned (71.5%), complete information concerning sleep bruxism was obtained for 864 children (438 girls and 426 boys; mean age: 7.9 ± 1.31 years; range= 6-11 years). Bruxism during sleep was reported as frequent or always present (Bruxers) in 76 children (8.8%), as occasionally present in 164 children (19.0%), and as never present (Never Bruxers) by 624 children (72.2%). The mean total score on the Rutter scale was 5.06 ± 5.37 (range= 0-33). Comparing Bruxers and Never Bruxers no significant differences were found with respect to behavioural disturbance (Mean total score =4.51±4.94 vs Mean total score =4.96±5.26; NS), emotional disturbance (Mean=1.74±1.07 vs Mean=1.89±1.12; NS) and conduct problems (Mean=3.47±1.42 vs Mean= 3.88±2.19; NS) as assessed by teachers on the Rutter scale. .

48.	Dourado, A.; Azevedo, M.H.; Macedo, A.; Coelho, I.M.; Valente, J.; Luis, A.; Soares, M.J.; Pato, C.N.; Pato, M.T.. 2000. "Reduced prevalence of psychoses in Santa Maria Island, Azores, Portugal.", Trabalho apresentado em VIIIth World Congress on Psychiatric Genetics, In American Journal Medical Genetics (Neuropsychiatric Genetics), Versailles, França. Objectives: To study the prevalence of psychoses in Santa Maria Island (Autonomous Region of Azores, Portugal). This island have a surface area of 97.24 Km², with a population of about 6,000 (4,332 aged 15 or older). Previous studies have reported a high degree of homogeneity in the Azorean population. Methods: Patients with psychoses (schizophrenia or bipolar affective disorder) were identified through providers of mental and general health services, which are all centralized in a Community Health Center. Cross information was obtained from these multiple informants, including the only psychiatrist of the island, the general practitioners, nurses and administrative personnel. After informed consent was given, patients were interviewed by psychiatrists using the DIGS (Diagnostic Interview for Genetic Studies) and an OPCRIT checklist were completed on a lifetime-ever basis, using all available data. All interviews were reviewed by a blind experienced psychiatrist and a consensus lifetime OPCRIT diagnosis was obtained. Conclusions: We found in the total population a low lifetime prevalence rate of schizophrenia and bipolar affective disorder (DSM-III-R and ICD- 10 criteria) of 2.4/1000 and 1.2/1000, respectively. In the population aged 15 years or over, the prevalence rate for each disorder was 3.2/1000 and 1.6/1000 respectively.

49.	Macedo, A.; Azevedo, M.H.; Valente, J.; Dourado, A.; Coelho, I.M.; Soares, M.J.; Pato, C.N.; Pato, M.T.. 2000. "Patterns of symptoms in patients with schizophrenia.", Trabalho apresentado em VIIIth World Congress on Psychiatric Genetics, In American Journal of Medical Genetics (Neuropsychiatric Genetics), Versailles, França. The purpose of this study was to determine the factor structure of OPCRIT psychotic items and its association with gender, age of onset and illness course in schizophrenia. A total of 108 patients with the diagnosis of schizophrenia (DSM-III-R), were assessed using the DIGS, and the OPCRIT checklist was completed on a lifetime basis. Twenty-six psychotic symptoms of the OPCRIT were selected and a principal component analysis with varimax rotation was performed. Two factors were extracted as determined by the screen test. Factor 1 labeled “paranoid” was composed of delusions (were these predominantly paranoid delusions or delusions in general) and hallucinations. Items loading on Factor 2 (non-paranoid) were mainly negative symptoms. No significant associations were found between each factor and age of onset. Statistically significant associations were found between Factor 1 and female sex (p=.015); and Factor 2 with male sex (p=.000) and a worse illness course (p=.016), as measured by ANOVA. Defining these factors or phenotypes might be useful in further genetic studies.

50.	Valente, J.; Azevedo, M.H.; Macedo, A.; Dourado, A.; Coelho, I.M.; Soares, M.J.; Pato, C.N.; Pato, M.T.; Kennedy, J.L.. 2000. "Clinical correlates of DRD4 genotypes in patients with schizophrenia", Trabalho apresentado em VIIIth World Congress on Psychiatric Genetics; Versailles (França), Agosto de 2000., In American Journal Medical Genetics (Neuropsychiatric Genetics), Versailles, França. The association between allele frequencies and genotypes of DRD4 and symptom dimensions in schizophrenic patients was studied. The sample includes 108 patients, 71 males and 37 females, with the diagnosis of schizophrenia (DSMIII-R). Two factor structure (Factor 1 labeled “paranoid”, Factor 2 non-paranoid) was obtained as shown by Azevedo et al (see companion Poster). All the patients were assessed using the DIGS, and the OPCRIT checklist was completed on a lifetime basis. Genomic DNA was extracted from blood cells by standard methods employing saturated sodium chloride solution. The polymerase chain reaction was carried out in a programmable heat block using Taq polymerase. The 48 bp repeat was detected by PCR. No significant associations were found between each factor and alleles 2, 4, 7, and “others” (3+5+6). Statistically significant associations were found between Factor 1 and the genotype 4,7 (p=.041) and with heterozygosity as compared with homozygosity (p=.019). This study suggests that the genotype (4,7) and heterozygosity of DRD4 alleles may constitute liability factors for development of specific dimensions of symptomatology (delusions and hallucinations) in patients with schizophrenia.

51.	Kennedy, J.L.; Pato, M.T.; Pato, C.N.; Azevedo, M.H.; Macedo, A.; Xu, J.; Vicente, A.. 1999. "Trinucleotide repeat analysis of Portuguese bipolar families showing anticipation", Trabalho apresentado em VIIth World Congress on Psychiatric Genetics, In Molecular Psychiatry, Monterey, E.U.A.

52.	Azevedo, M.H.; Soares, M.J.; Coelho, I.M.; Dourado, A.; Valente, J.; Macedo, A.; Pato, M.T.; Pato, C.N.. 1998. "Using consensus OPCRIT diagnoses: an efficient procedure for best estimate life-time diagnoses.", Trabalho apresentado em VIth World Congress on Psychiatric Genetics, In American Journal of Medical Genetics (Neuropsychiatric Genetics), Bona, Alemanha. Objective: The OPCRIT polydiagnostic system, which comprises a 90-item checklist of signs and symptoms and a suite of computer programs, generates diagnoses according to 12 operational diagnostic systems (e.g., DSM-III, DSM-III-R, RDC, ICD-10). We examined the agreement of the diagnoses generated by the OPCRIT system with a best-estimate lifetime procedure, from ratings produced by clinicians involved in molecular genetic research. Method: The sample included 140 subjects from large multigenerational bipolar or schizophrenic pedigrees (n=100), and from a sample of unrelated schizophrenic subjects (n=40). Our approach compares, for each subject, two scores of OPCRIT checklist. One was made by independent interviewers, using the Diagnostic Interview for Genetic Studies. The other was a consensual OPCRIT score made by a group of three trained raters (clinical research), blind for subjects diagnosis, based in DIGS information. OPCRIT-generated diagnoses were compared and accepted if in agreement. In case of disagreement, all the raters discuss the OPCRIT ratings and resolve disagreements to produce a consensus OPCRIT checklist used to generate the final set of diagnoses. Using Cohen kappa statistic, we analyzed the diagnostic agreement according to DSM-III-R and ICD-10. Results: Results proved excellent agreement between OPCRIT diagnoses from clinicians and OPCRIT diagnoses made by consensus procedure for DSM-III-R (k=0.83) and ICD-10 (k=0.81). We also found excellent agreement between interviewer diagnoses and final diagnoses (DSM-III-R, k=0.88; ICD-10, k=0.88) and between consensus and final diagnoses ( DSM-III-R, k=0.89; ICD-10, k=0.92). Conclusion: Results of the present study suggest that this procedure of diagnosis assessment is an efficient alternative to classic best estimate diagnoses procedure.

53.	Pato, C.N.; Macedo, A.; Ambrósio, A.; Vincent, J.B.; Bauer, A.; Schindler, K.M.; Xu, J.; Coelho, I.M.; Dourado, A.; Valente, J.; Pato, M.T.; Azevedo, M.H.; Kennedy, J.L.. 1998. "Detection of expansion regions in bipolar families", Trabalho apresentado em VIth World Congress on Psychiatric Genetics, In American Journal of Medical Genetics (Neuropsychiatric Genetics), Bona, Alemanha. Objective: We have studied 24 families with multiple affected members suffering from bipolar disorder to test the hypothesis that in those families clinically showing genetic anticipation (Macedo et al, separate preparation) we would find large repeat expansions. Methods: The families meeting inclusion criteria had to have a minimum of two affected members over two generations and showed marked anticipation both in terms of age of onset and disease severity. We utilized the RED method to test patients (n=26) and controls (n=23) from these families, as well as, unrelated controls (n=41). We also genotyped patients with large expansions at the common loci at ch.17 and 18. Results: The RED method revealed a higher number of large expansions in patients compared to controls (p<0.002). The patients with the largest expansions were typed at ch.17 and 18 and their expansions were not at these two common regions. Conclusion: Genetic anticipation was further analyzed correcting for potential ascertainment bias, possible proband effects, cohort effects, regression to the mean, gender effects, and maternal versus paternal transmission. None of these potential confounds appear to account for the observed anticipation. We have also identified that the presence of large expansions in affected family members derives primarily from two families from a genetically isolated population. These expansions do not appear to be one of the common expansions on chromosomes 17 and 18.

54.	Macedo, A.; Azevedo, M.H.; Coelho, I.M.; Dourado, A.; Valente, J.; Soares, M.J.; Pato, M.T.; Macciardi, F.; Pato, C.N.. 1998. "Genetic Anticipation in Portuguese families with Bipolar Affective Disorder.", Trabalho apresentado em VIth World Congress on Psychiatric Genetics, In American Journal of Medical Genetics (Neuropsychiatric Genetics), Bona, Alemanha. Objective: Genetic anticipation refers to an inheritance pattern within a pedigree with a decrease in age of onset or increase in disease severity or both in successive generations. This phenomenon has become the focus of important research in major psychiatric disorders, namely schizophrenia and bipolar affective disorder (BPAD). Since anticipation is now known to result from expansion of unstable trinucleotide repeat sequences in several neuropsychiatric disorders, and if such an effect is found in families manifesting BPAD, which is the objective of the present study, the implication of dynamic mutations in the genetic aetiology of BPAD would be a serious possibility. Method: In this study, we compared anticipation measures (age at onset and disease severity) between two generations in 24 Portuguese families ascertained for genetic linkage studies of BPAD. Results: There was a significant decrease in age at onset (P < 0.00001) and increase in frequency of episodes (P < 0.0001) from the first to the second generation. This difference was significant under each of the four datasampling schemes, one of which excluded probands. The younger generation (G2) experienced onset 12.4 - 15.9 years earlier and illness 2.3 - 2.6 times more severe than did the parental generation (G1). We found no evidence for a specific effect in anticipation related to the sex of the transmitting parent. Conclusion: Results of the present study suggest evidence for genetic anticipation in our sample of families.

55.	Macedo, A.; Valente, J.; Dourado, A.; Coelho, I.M.; Vicente, A.; Ambrósio, A.; Sasaki, T.; Pato, C.N.; Pato, M.T.; Azevedo, M.H.; Kennedy, J.L.. 1997. "Assessment for unstable DNA in schizophrenia in a Portuguese population: association with anticipation.", Trabalho apresentado em Vth World Congress on Psychiatric Genetics, In Journal of Medical Genetics (Neuropsychiatric Genetics), Santa Fé, E.U.A..

56.	Coelho, I.M.; Macedo, A.; Valente, J.; Dourado, A.; Ambrósio, A.; King, N.; Azevedo, M.H.; Kennedy, J.L.; Pato, C.N.; Pato, M.T.. 1997. "Association study of Serotonin receptors and schizophrenia in a Portuguese population. ", Trabalho apresentado em Vth World Congress on Psychiatric Genetics, In American Journal of Medical Genetics (Neuropsychiatric Genetics), Santa Fé, E.U.A..

57.	Dourado, A.; Coelho, I.M.; Macedo, A.; Valente, J.; Fourie, O.; Ambrósio, A.; Pato, C.N.; Pato, M.T.; Azevedo, M.H.; Kennedy, J.L.. 1997. "Linkage and association studies of DRD3 and schizophrenia in Portuguese patients: Effect of population stratification.", Trabalho apresentado em Vth World Congress on Psychiatric Genetics, In American Journal of Medical Genetics (Neuropsychiatric Genetics), Santa Fé, E.U.A.

58.	Valente, J.; Dourado, A.; Coelho, I.M.; Macedo, A.; Ambrósio, A.; King, N.; Kennedy, J.L.; Azevedo, M.H.; Pato, M.T.; Pato, C.N.. 1997. "Association between DRD4 and schizophrenia in a Portuguese population.", Trabalho apresentado em Vth World Congress on Psychiatric Genetics, In American Journal of Medical Genetics (Neuropsychiatric Genetics), Santa Fé, E.U.A..

59.	Vicente, A.; Ambrósio, A.; Coelho, I.M.; Valente, J.; Dourado, A.; Macedo, A.; Pato, C.N.; Oliveira, C.R.; Azevedo, M.H.. 1997. "Psychosis in the Portuguese mainland and Azorian population: linkage and association analysis of candidate genes for schizophrenia.", Trabalho apresentado em Vth World Congress on Psychiatric Genetics; Santa Fé (E.U.A), Outubro de 1997., In American Journal of Medical Genetics (Neuropsychiatric Genetics), Santa Fé, E.U.A..

60.	Vincent, J.B.; Meltzer, H.Y.; Lieberman, J.A.; Breschel, T.; MCGinnis, M.; Macedo, A.; Azevedo, M.H.; Pato, C.N.; Torrey, E.F.; Gottesman, I.I.; Petronis, A.; Kennedy, J.L.. 1997. "Large or expanded CAG/CTG trinucleotide repeats as an etiological factor in schizophrenia.", Trabalho apresentado em VIth International Congress on Schizophrenia Research, In Schizophrenia Research, Colorado Springs, E.U.A.. Abstract: Many diseases that show anticipation (increased severity/decreased age of onset in successive generations) have recently been shown to have expanded trinucleotide repeats either within or adjacent to the disease causing gene. Evidence of anticipation in schizophrenia has led us to search for large or expanded trinucleotide repeats that may be associated with a disease causing gene. Using the Repeat Expansion Detection (RED) technique, we have performed a matched pair analysis on 99 schizophrenia patients from North America and 99 controls matched for age sex and ethnicity. A second sample of 76 Portuguese schizophrenics and 46 controls was also analysed for evidence of CAG repeat expansion. No significant differences in CAG/CTG repeat sizes were observed for schizophrenia affecteds and matched controls, using a (CTG)10 oligonucleotide. No evidence of intergenerational instability was observed amongst 14 schizophrenia triads. Furthermore, no significant sex effect was observed, and no significant differences in repeat size were found for responders and non-responders to clozapine. There was no significant correlation (either positive or negative) between age of onset of disease and size of repeat. In a study of MZ twins discordant for schizophrenia the presence of larger RED product in the affected twin was not observed. The 7,6A CAG repeat on 18q21 also showed no differences between twins. We thus cannot conclude that CAG/CTG trinucleotides are involved in psychotic disorders and that either the differences observed in other similar studies may be the result of population stratification (Sirugo et al., 1995) or that the increased occurrence of larger repeats amongst affected individuals is a much smaller effect than previously thought. However, the techniques used for detecting repeat expansions are of limited sensitivity. The involvement of other trinucleotide repeats or other expandable repeat sequences cannot be ruled out. .

61.	Spurlock, G.; Williams, J.; Daniels, J.; Owen, M.J.; Mallet, J.; Laurent, C.; Aschauer, H.N.; Fuchs, K.; Macciardi, F.; Verga, M.; Propping, P.; Nöthen, M.; Azevedo, M.H.; Pato, C.N.; Macedo, A.; Mors, O.; Petterson, U.; Sundvall, M.; Gill, M.; McKeon, P.. 1995. "The European multi-centre study of susceptibility gene associations in schizophrenia: typing the 5HT-2R gene.", Trabalho apresentado em World Congress of Psychiatric Genetics, In Psychiatric Genetics, California, U.S.A..

62.	Azevedo, M.H.; Dourado, A.; Valente, J.; Macedo, A.; Coelho, I.M.; Pato, M.T.; Pato, C.N.. 1993. "The Portuguese-Language Version of the Diagnostic Interview for Genetic Studies.", Trabalho apresentado em IIIrd World Congress on Psychiatric Genetics, In American Journal of Medical Genetics (Psychiatric Genetics), New Orleans, E.U.A..

Textos em jornais ou revistas Texts in newspapers or magazines

1.	Pereira, A.T.; Maia, B.R.; Soares, M.J.; Bos, S.C.; Marques, M.; Valente, J.; Nogueira, V.; Azevedo, M.H.; Macedo, A.. 30 jun. 2011. "Teste de Atitudes Alimentares 25 - Validade para o rastreio das Perturbação do Comportamento Alimentar."  Psiquiatria Clínica, 89 - 104.

2.	Nogueira, V.; Valente, J.; Soares, M.J.; Pereira, A.T.; Bos, S.C.; Marques, M.; Maia, B.; Macedo, A.; Azevedo, M.H.. 30 mar. 2011. "Comportamento Suicidário na Esquizofrenia." Psiquiatria Clínica, 17 - 27.

3.

Cabral, A.S.; Macedo, A.; Vieira, D.N.. 30 abr. 2009. "Da Psiquiatria ao Direito" Julgar, Nº7: 185-196, 2009., 185 - 196. Após uma breve introdução, é feito um enquadramento jurídico-penal da doença mental, bem como uma descrição sumária do conceito de inimputabilidade. É ainda considerada a questão da aplicação das medidas de segurança, citando-se a contribuição dos autores que mais se têm salientado neste campo e as actuais perspectivas sobre o tema.

4.

Cabral, A.S.; Macedo, A.; Vieira, D.N.. 30 dez. 2008. "Da Doença Mental à Violência." Saúde Mental, Volume X (6): 13-20, 2008., 13 - 20. Os comportamentos violentos no âmbito da doença mental têm sido motivo de intenso debate e crescente investigação. A complexidade da questão e a sua importância clínica e social moveram-nos na elaboração do presente artigo, com o qual pretendemos, a partir de uma revisão da literatura existente, a contextualização daquela relação à luz dos actuais conhecimentos científicos.

5.	Macedo, A.; Soares, M.J.; Maia, B.R.; Pereira, A.T.; Marques, M.; Bos, S.C.; Gomes, A.A.; Azevedo, M.H.. 30 set. 2007. "Perfeccionismo e psicopatologia." Psiquiatria Clínica, 5 - 14.

6.	Cabral, A.S.; Macedo, A.; Valente, J.; Soares, M.J.; Vieira, D.N.; Azevedo, M.H.. 30 set. 2007. "Perturbações Psicóticas e Conduta Criminal – um contributo empírico." Psiquiatria Clínica, 85 - 96.

7.	Macedo, A.; Soares, M.J.; Gomes, A.A.; Marques, M.; Pereira, A.T.; Maia, B.; Bos, S.C.; Pato, M.T.; Azevedo, M.H.. 30 dez. 2006. "Comportamento alimentar e perfeccionismo."  Psiquiatria Clínica, 297 - 307.

8.	Santos, M.L.; Maia, B.R.; Soares, M.J.; Pocinho, F.; Macedo, A.. 30 set. 2006. "Perturbação Obsessivo-Compulsiva – Será que o Género Importa?" Psiquiatria Clínica, 235 - 242.

9.	Maia, B.R.; Pereira, A.T.; Soares, M.J.; Bos, S.C.; Cabral, A.S.; Valente, J.; Macedo, A.; Pocinho, F.; Azevedo, M.H.. 30 mar. 2006. "Perfeccionismo e Perturbações do Espectro Obsessivo-Compulsivo – resultados preliminares." Psiquiatria Clínica, 63 - 69.

10.	Pereira, A.T.; Soares, M.J.; Maia, B.R.; Bos, S.C.; Cabral, A.S.; Macedo, A.; Ferreira, C.P.; Azevedo, M.H.. 30 mar. 2006. "A Versão Portuguesa Reduzida do Teste de Atitudes Alimentares-40." Psiquiatria Clínica, 51 - 61.

11.	Pereira, A.T.; Maia, B.R.; Cabral, A.S.; Soares, M.J.; Bos, S.C.; Macedo, A.; Azevedo, M.H.. 30 jun. 2005. "Distúrbios do Comportamento Alimentar no Sexo Masculino." Psiquiatria Clínica, 83 - 96.

12.	Macedo, A.; Azevedo, M.H.; Coelho, I.M.; Dourado, A.; Valente, J.; Soares, M.J.; Cabral, A.S.; Kennedy, J.L.; Pato, M.T.; Pato, C.N.. 30 dez. 2004. "Kraepelin e a dicotomia das psicoses: evidências moleculares." Psiquiatria Clínica, 245 - 257.

13.	Soares, M.J.; Macedo, A.; Gomes, A.A.; Azevedo, M.H.. 30 mar. 2004. "Versão Portuguesa do Teste de Atitudes Alimentares-40."  Psiquiatria Clínica, 5 - 19.

14.	Soares, M.J.; Gomes, A.A.; Macedo, A.; Santos, V.; Azevedo, M.H.. 30 jun. 2003. "Escala MultiDimensional de Perfeccionismo: Adaptação à População Portuguesa." Revista Portuguesa de Psicossomática, 46 - 55.

15.	Macedo, A.; Azevedo, M.H.; Pocinho, F.; Soares, M.J.; Dourado, A.; Campos, C.; Domingues, O.; Pato, M.T.. 30 set. 2002. "Perfeccionismo – uma dimensão fenotípica comum aos fenómenos obsessivos e distúrbios alimentares?" Psiquiatria Clínica, 163 - 174.

16.	Valente, J.; Azevedo, M.H.; Macedo, A.; Dourado, A.; Coelho, I.M.; Soares, M.J.; Pato, C.N.; Pato, M.T.; Kennedy, J.L.. 30 jun. 2002. "Estrutura Dimensional dos Sintomas Esquizofrénicos com o Sistema OPCRIT." Psiquiatria Clínica, 91 - 102.

17.	Dourado, A.; Azevedo, M.H.; Macedo, A.; Coelho, I.M.; Valente, J.; Soares, M.J.; Pires, A.L.; Pato, C.N.; Pato, M.T.. 30 jun. 2002. "Prevalência dos Distúrbios Psicóticos Major Na Ilha De Santa Maria, Região Autónoma Dos Açores." Psiquiatria Clínica, 103 - 111.

18.	Valente, J.; Azevedo, M.H.; Macedo, A.; Dourado, A.; Coelho, I.M.; Soares, M.J.; Pato, C.N.; Kennedy, J.L.. 30 jun. 2002. "Correlatos Clínicos do gene DRD4 em Doentes com Esquizofrenia." Psiquiatria Clínica, 175 - 186.

19.	Macedo, A.; Dourado, A.; Valente, J.; Coelho, I.M.; Soares, M.J.; Santos, V.; Azevedo, M.H.. 30 mar. 2002. "Comportamento Suicida: alguns aspectos neurobiológicos."  Psiquiatria Clínica, 29 - 41.

20.	Macedo, A.; Azevedo, M.H.; Pocinho, F.. 30 jun. 2000. "Distúrbio Obsessivo-Compulsivo: Alguns aspectos genéticos"  Revista do Hospital Júlio de Matos, 129 - 139.

21.	Azevedo, M.H.; Macedo, A.; Dourado, A.; Valente, J.; Coelho, I.M.; Soares, M.J.. 30 mar. 2000. "Grupo de Estudos de Genética Psiquiátrica: Uma Década de Actividades"  Psiquiatria Clínica, 13 - 22.

22.	Macedo, A.. 30 jun. 1999. "Esquizofrenia e Neurodesenvolvimento: um modelo explicativo."  Psiquiatria Clínica, 109 - 123.

23.	Macedo, A.; Pocinho, F.. 30 jun. 1999. "Hipocondria: organização cognitiva de estilo obsessivo" Psiquiatria Clínica, 185 - 194.

24.	Macedo, A.; Azevedo, M.H.; Coelho, I.M.; Dourado, A.; Valente, J.; Soares, M.J.; Pato, M.T.; Pato, C.N.; Macciardi, F.. 30 set. 1998. "Antecipação Genética: Um estudo em famílias Portuguesas com Distúrbio Afectivo Bipolar." Psiquiatria Clínica, 165 - 173.

25.	Azevedo, M.H.; Macedo, A.; Dourado, A.; Coelho, I.M.; Ambrósio, A.; Valente, J.. 30 abr. 1998. "Genética da Doença Afectiva Bipolar."  Revista de Psiquiatria, 27 - 37.

26.

Soares, M.J.; Dourado, A.; Macedo, A.; Valente, J.; Coelho, I.M.; Azevedo, M.H.. 30 mar. 1997. "Estudo de Fidelidade da Lista de Critérios Operacionais Para Doenças Psicóticas." Psiquiatria Clínica, 11 - 24. Nos nossos estudos de genética molecular de esquizofrenia e distúrbio afectivo bipolar, um dos instrumentos usados para avaliação psicopatológica de probandos e familiares é o sistema OPCRIT. Os autores apresentam o resultado do estudo de fidelidade inter-avaliador do sistema OPCRIT efectuado entre os membros da equipa. A concordância item por item e em relação aos diagnósticos obtidos foi boa.

27.

Pato, C.N.; Pato, M.T.; Kennedy, J.L.; Faraone, S.; Schindler, K.M.; Coelho, I.M.; Valente, J.; Dourado, A.; Macedo, A.; Madeira, J.; Moniz, M.; Ferreira, C.P.; Azevedo, M.H.. 30 mar. 1997. "Methodology and Statistical Power of the Portuguese Genetics of Psychosis Project." Psiquiatria Clínica, 35 - 40. PT: Tornou-se claro que para descobrir genes que estejam etiologicamente envolvidos na vulnerabilidade para doenças psiquiátricas, é necessário desenhar e analisar os estudos de um modo compatível com a natureza de transmissão complexa dessas doenças. Para ter em conta essa natureza complexa do estudo dos distúrbios psicóticos, desenhámos uma abordagem baseada na população relativamente homogénea dos Açores, utilizando estratégias analíticas convergentes, uma cuidadosa definição do fenótipo e estudos colaborativos. Para além disso, é importante que seja estudado o poder estatístico do tamanho das amostras, de modo a aumentar a confiança nos resultados obtidos. Neste artigo, efectuamos uma revisão dos métodos deste estudo e do poder estatístico da amostra proposta. EN: It is becoming increasingly clear that to find genes for psychiatric disorders, we must design and analyze studies in a manner that is suitable for complex diseases. We have designed an approach to study psychotic disorders based upon a relatively homogeneous population of the Azores using converging analytic strategies, careful definition of phenotype and other collaborative studies to help address the complexity of the disease. In addition, it is important that statistically powerful sample sizes are studied in order to gain confidence in the obtained results. In this paper, we review the methods of this study and the statistical power of the proposed sample.

28.

Coelho, I.M.; Macedo, A.; Valente, J.; Dourado, A.; Ambrósio, A.; King, N.; Azevedo, M.H.; Kennedy, J.L.; Pato, C.N.; Pato, M.T.. 30 mar. 1997. "Association study of Serotonin receptors and schizophrenia in a Portuguese population." Psiquiatria Clínica, 41 - 47. PT: O papel da serotonina na esquizofrenia tem sido analisada numa variedade de estudos, mas o interesse aumentou desde o crescente número de antipsicóticos com marcada afinidade para os receptores serotoninérgicos. Seleccionámos uma população Portuguesa. De doentes com esquizofrenia segundo a DSM-IV (n=87) e de controles (n=43). Foram genotipados, usando a técnica CPR, polimorfismos nos genes receptores de 5HT1D-alfa, 5HT1D-beta, 5HT2, e na região promotora do gene transportador da serotonina. Foi detectada uma associação significativa entre Esquizofrenia e o locus 5HT1D-alfa (p<0.002). Este achado pode reflectir uma maior capacidade para detectar efeitos genéticos em subtipos específicos de esquizofrenia, numa população homogénea. EN: The role of serotonin in schizophrenia has been implicated in a variety of studies, but has been of greater interest since the development of an increasing number of atypical antipsychotics with strong affinity for the serotonin receptors. We selected a Portuguese population of patients with DSM-IV schizophrenia (n = 87) and Portuguese controls (n = 43). Polymorphisms in the 5HT1D-alpha, 5HT1D-beta and 5HT2 receptor genes, and in the promoter region of the serotonin transporter gene were genotyped using the Polymerase Chain Reaction (PCR). A statistically significant association between schizophrenia and the 5HT1D-alpha locus was found (p <0.002). The identification of this association may reflect the increase power to detect genetic effects in specific subtypes of schizophrenia in a homogeneous population.

29.	Macedo, A.; Azevedo, M.H.. 30 mar. 1997. "Antecipação Genética e Distúrbio Afectivo bipolar." Psiquiatria Clínica, 69 - 77.

30.

Dourado, A.; Coelho, I.M.; Macedo, A.; Valente, J.; Fourie, O.; Ambrósio, A.; Pato, C.N.; Pato, M.T.; Azevedo, M.H.; Kennedy, J.L.. 30 mar. 1997. "Linkage and association studies of DRD3 and schizophrenia in Portuguese patients: Effect of population stratification"  Psiquiatria Clínica, 49 - 53. PT: Tem sido sugerido em estudos prévios uma relação entre o receptor da dopamina D3 e a esquizofrenia. O polimorfismo do receptor da dopamina D3 origina uma alteração num aminoácido desse receptor. Numa amostra de 87 doentes com esquizofrenia e 57 controlos emparelhados etnicamente e 11 famílias com pelo menos dois elementos afectados, foram efectuadas análises de associação standard e análises paramétricas de linkage. Tanto os estudos de associação como os de linkage não confirmam o papel do receptor da dopamina D3 na esquizofrenia, não sendo no entanto de excluir o seu efeito numa pequena parte da população ou mesmo um efeito modificador. EN: Previous studies have suggested a relationship between the Dopamine D3 receptor gene (DRD3) and schizophrenia. The DRD3 polymorphism results in an amino acid change in the receptor protein. We have studied 87 patients and 57 ethnically matched controls, and 11 medium sized families each with at least two patients. Standard association and parametric linkage analyses were performed. Both association and linkage studies failed to confirm a role for DRD3 in schizophrenia in our sample, but can not rule out an effect in a small portion of the population or a modifier effect.

31.

Valente, J.; Dourado, A.; Coelho, I.M.; Macedo, A.; Ambrósio, A.; King, N.; Kennedy, J.L.; Azevedo, M.H.; Pato, M.T.; Pato, C.N.. 30 mar. 1997. "Association between DRD4 and schizophrenia in a Portuguese population."  Psiquiatria Clínica, 55 - 59. PT: Várias linhas de evidência apontam para um papel do gene do receptor D4 da dopamina (DRD4) na esquizofrenia. Seleccionámos uma população de doentes Portugueses com o diagnóstico de esquizofrenia pela DSM-IV (n = 87) e controlos portugueses (n = 54). O polimorfismo de repetição de 48 pares de base no terceiro exão da DRD4 foi genotipado usando a reação de polimerização em cadeia (PCR). Ao contrário de estudos prévios do DRD4 em doentes com esquizofrenia pertencentes a outras populações, uma associação estatisticamente significativa entre esquizofrenia e DRD4 foi encontrada (p = 0,007). A identificação desta associação, em contraste com estudos prévios em outras populações, pode reflectir o aumento do poder para detectar efeitos genéticos em subtipos específicos de esquizofrenia numa população homogénea. EN: Several lines of evidence point a role for the dopamine D4 receptor gene (DRD4) in schizophrenia. We selected a Portuguese population of patients with DSM-IV schizophrenia (n = 87) and Portuguese controls (n = 54). The 48 base pair repeat polymorphism in the third exon of DRD4 was genotyped using the Polymerase Chain Reaction (PCR). Unlike previous studies of DRD4 in schizophrenia in patients drawn from other populations, a statistically significant association between schizophrenia and DRD4 was found (p = 0.007). The identification of this association, in contrast with previous studies in other populations, may reflect the increased power to detect genetic effects in specific subtypes of schizophrenia in a homogeneous population.

32.	Macedo, A.; Valente, J.; Dourado, A.; Coelho, I.M.; Vicente, A.; Ambrósio, A.; Sasaki, T.; Pato, C.N.; Azevedo, M.H.; Kennedy, J.L.. 30 mar. 1997. "Assessment for unstable DNA in schizophrenia in a Portuguese population: association with anticipation." Psiquiatria Clínica, 61 - 67.

33.

Macedo, A.; Azevedo, M.H.. 30 jun. 1996. "A esquizofrenia é uma doença do cérebro: implicações genéticas de um modelo neurodesenvolvimental da esquizofrenia"  Psiquiatria Clínica, 67 - 81. Neste trabalho, os autores efectuam uma breve revisão das alterações cerebrais estruturais nos doentes esquizofrénicos que suportam a conceptualização da esquizofrenia como um distúrbio neurodesenvolvimental e as consequentes implicações desse modelo para a investigação genética do distúrbio.

34.

Pocinho, F.; Macedo, A.; Pato, M.T.. 30 jun. 1996. "Tratamento do Distúrbio Obsessivo-Compulsivo: abordagem farmacológica e cognitivo-comportamental" Psiquiatria Clínica; 17 (2): 93-107, 1996., 93 - 107. Os autores fazem uma revisão da terapêutica farmacológica do distúrbio obsessivo-compulsivo, bem como dos modelos e técnicas de terapia cognitivo-comportamental, colocando a ênfase na aplicação de estratégias combinadas e interdisciplinares, como meio de potenciar os efeitos terapêuticos.

35.

David, A.C.; Azevedo, M.H.; Pocinho, F.; Macedo, A.; César, H.; Ferreira, A.M.; Gomes, F.A.. 30 jun. 1996. "Doentes com Distúrbio Obsessivo-Compulsivo Num Hospital de Dia: Casuística de nove anos" Psiquiatria Clínica, 109 - 114. Neste trabalho, os autores analisam as características sócio-demográficas e clínicas de todos os doentes com o diagnóstico de Distúrbio Obsessivo-Compulsivo, internados no Hospital de dia da clínica Psiquiátrica dos Hospitais da Universidade de Coimbra, desde a sua abertura em 1987 até ao presente.

36.

Macedo, A.; Coelho, I.M.; Azevedo, M.H.. 30 jun. 1995. "Distúrbios do Espectro Esquizofrénico: Esquizotipia" Psiquiatria Clínica, 87 - 97. Os autores fazem uma revisão da evolução histórica do conceito esquizofrenia, um dos distúrbios do designado espectro esquizofrénico. Os dados dos estudos familiares, de adopção e de gémeos apontam para a existência de uma relação genética entre a esquizotipia e a esquizofrenia.

37.

Macedo, A.; Pato, C.N.; Azevedo, M.H.. 30 mar. 1995. "Genética dos Distúrbios Afectivos: II. Estudos de Linkage e Associação" Psiquiatria Clínica, 11 - 24. Neste trabalho, os autores fizeram uma breve revisão dos modelos de transmissão genética e dos estudos de linkage e associação dos distúrbios afectivos, realçando que os melhoramentos técnicos da genética molecular, combinados com novos modelos de análise e de transmissão, poderão contribuir para a descoberta dos factores genéticos envolvidos na etiologia, neste tipo de distúrbios psiquiátricos.

38.

Macedo, A.; Pato, C.N.; Azevedo, M.H.. 30 dez. 1994. "Genética dos Distúrbios Afectivos: I. Epidemiologia Genética" Psiquiatria Clínica, 171 - 185. Neste trabalho, os autores fizeram uma revisão da literatura dos estudos de epidemiologia genética dos distúrbios afectivos, com particular referência para o distúrbio afectivo bipolar. A revisão dos estudos familiares, de gémeos e de adopção, favorece a hipótese de que os factores genéticos desempenhem um papel etiológico importante, nestes distúrbios.

39.

Valente, J.; Macedo, A.; Dourado, A.; Coelho, I.M.; Azevedo, M.H.. 30 set. 1994. "Diagnóstico psiquiátrico na investigação: abordagem polidiagnóstica" Psiquiatria Clínica, 131 - 135. Uma estratégia diagnóstica designada como polidiagnóstica, tem vindo a ser usada de modo a contornar o problema da existência de múltiplos sistemas diagnóstico operacionais diferentes, competindo na prática da investigação psiquiátrica. Neste trabalho, os autores fazem uma revisão desta abordagem, suas vantagens e desvantagens e da experiência que dela têm, no seu trabalho de investigação.

40.

Macedo, A.; Azevedo, M.H.. 30 jun. 1994. "Genética da Esquizofrenia: revisão dos contributos mais recentes" Psiquiatria Clínica, 65 - 77. Neste trabalho, os autores fazem uma revisão dos contributos mais antigos, bem como dos mais recentes na genética da esquizofrenia, tanto no campo da epidemiologia genética (estudos familiares, de gêmeos e de adopção), como no campo da genética molecular, pondo em relevo que só uma estratégia concertada destas duas abordagens, poderá produzir resultados positivos em relação ao esclarecimento etiológico do substrato genético da esquizofrenia.

41.	Macedo, A.. 29 jun. 1994. "Diabetes e Férias" Boletim da Associação dos Diabéticos da Zona Centro, 0 - 0.

42.

Azevedo, M.H.; Valente, J.; Macedo, A.; Dourado, A.; Coelho, I.M.; Pato, M.T.; Pato, C.N.. 31 dez. 1993. "Versão Portuguesa da “Entrevista Diagnóstica para Estudos Genéticos”" Psiquiatria Clínica, 213 - 217. Nos nossos estudos de genética molecular da Esquizofrenia e Distúrbios Afectivos Bipolares, os instrumentos usados para a avaliação psicopatológica de probandos e familiares, inclui a “Entrevista Diagnóstica para Estudos Genéticos”, desenvolvida pelos “Diagnostic Centers for Psychiatric Linkage Studies” dos E.U.A. Este novo instrumento avalia a presença de sinais e sintomas em toda a vida, fornecendo disgnósticos segundo diferentes sistemas de classificação, incluindo a DSM-III-R e CID-10. O propósito deste trabalho é descrever os procedimentos seguidos para uma tradução que fosse facilmente entendida por indivíduos de diversos estatutos sócio-culturais, mantendo-se no entanto, semânticamente equivalente à versão original da língua Inglesa. A versão Portuguesa da entrevista já começou a ser usada na avaliação de alguns heredogramas, e esta experiência inicial tem sido bastante satisfatória.

43.

Macedo, A.; Pocinho, F.. 31 dez. 1993. "Fobia Social e Personalidade Evitante: a propósito da sua delimitação à luz do modelo cognitivo-comportamental" Psiquiatria Clínica, 243 - 256. A propósito do caso clínico de um doente com 2 diagnósticos co-mórbidos (Fobia Social e Distúrbio da Personalidade Evitante), os autores tecem algumas considerações sobre a natureza das relações e delimitações entre os distúrbios do Eixo I e do Eixo II da DSM-III/III-R. Relativamente aos dois distúrbios em título, procura-se fazer uma delineação dos principais determinantes cognitivo-comportamentais que possam contribuir para a sua delimitação conceptual e clínica.

44.

Macedo, A.; Pocinho, F.. 30 set. 1993. "Hipocondria" Psiquiatria Clínica, 171 - 180. No presente artigo, os autores fazem uma revisão do conceito de Hipocondria, nas vertentes histórica, clínica e epidemiológica, dando especial ênfase aos recentes contributos do modelo cognitivo-comportamental na compreensão deste distúrbio, bem como referência a algumas estratégias terapêuticas nascidas deste modelo que se apresentam como alternativas promissoras nestes campo.

45.

Macedo, A.; Valente, J.; Dourado, A.; Coelho, I.M.; Azevedo, M.H.. 30 jun. 1993. "Algumas Questões sobre o Diagnóstico na Investigação Biológica em Psiquiatria" Psiquiatria Clínica, 117 - 125. Os autores fazem uma breve análise das causas da baixa fidedignidade dos diagnósticos psiquiátricos, bem como das estratégias desenvolvidas para diminuir os problemas nessa área, nomeadamente a introdução dos critérios operacionais e estandardização da colheita de informação. Embora a melhoria da fidedignidade tenha constituído um indesmentível progresso, o problema da validade mantem-se, pelo que a tendência actual em investigação recomenda a utilização simultânea de várias definições diagnósticas.

46.

Macedo, A.. 31 dez. 1992. "Cefaleias de Tensão – Revisão Teórica" Psiquiatria Clínica, 199 - 207. Neste trabalho de revisão sobre as cefaleias de tensão, o autor procura dar uma perspetiva geral do tema à luz das contribuições mais recentes, abordando aspetos relativos à definição, clínica e patogénese. Foi igualmente abordada a implicação dos fatores psicológicos na etiologia e tratamento do distúrbio. NB: O dia desta publicação, poderá não estar 100% correcta.

47.

Macedo, A.. 31 mar. 1992. "Pânico e Agorafobia" Psiquiatria Clínica, 25 - 40. Este trabalho foi elaborado com fins didáticos, tendo sido apresentado numa sessão teórica da Consulta de Terapia Comportamental, destinada à formação dos estagiários de Psicologia. O autor procura dar uma perspetiva geral do fenómeno pânico, abordando aspetos tais como a evolução histórica do conceito, aspetos epidemiológicos e clínicos, facotes de vulnerabilidade genética e familiar, aspetos neurobioquímicos da etiologia do pânico e finalmente alguns aspetos de terapêutica farmacológica do pânico. Não foi abordado o modelo cogintivo-comportamental do pânico, nem as estratégias terapêuticas decorrentes desse modelo, visto que esse tema era objeto de uma sessão independente efectuada por outros autores. NB: O dia desta publicação, poderá não estar 100% correcta.

48.

Macedo, A.; Saraiva, C.B.; Travassos, M.. 30 out. 1991. "Distúrbio de Gilles de la Tourette - a propósito de dois casos clínicos" Psiquiatria Clínica, 135 - 149. No presente artigo os autores revêem a literatura médica do Distúrbio de Gilles de la Tourette e apresentam dois casos raros do síndrome, sendo o primeiro reportado a uma doente de 25 anos com tiques orofaciais, da cabeça, pescoço e abdómen, que remontam aos 12 anos, com agravamento aos 21 anos, por pestanejos e fungadas e coprolália tardia. Dúvidas obsessivas e rituais de verificação acompanham o quadro clínico. Conflitos conjugais graves relacionados com a cabeça estavam presentes. o EEG mostrava ondas lentas frontais bilaterais. Respondeu favoravelmente ao pimozide (2mg/dia) e à psicoterapia de saciação para tiques. o segundo caso reportado a uma doente de 29 anos com tiques múltiplos variando ao longo dos anos, iniciados aos 5 por tricotilomia seguida de pestanejos e fungadas, com aritmomania, verificações compulsivas e tiques com os ombros a partir da adolescência. Nos últimos anos surgiram tiques abdominais, rituais de lavagem e cheirar compulsivo de objectos e alimentos. Respondeu favoravelmente ao haloperidol (1,5mg/dia). NB: O dia desta publicação, poderá não estar 100% correcta.

49.

Macedo, A.. 28 jun. 1991. "Despersonalização" Psiquiatria Clínica, 69 - 75. Este trabalho foi preparado para ser apresentado numa sessão de formação teórica destinada aos médicos internos de Psiquiatria. Nele se procura fazer uma revisão teórica do conceito de despersonalização, sua evolução e perspectivas actuais. NB: O dia desta publicação, poderá não estar 100% correcta.

Tradução Translation

1.

Treasure, J.; Schmidt, U.H.; Nunes, T.; Azevedo, M.H.; Macedo, A.; Ferreira, A.M.. 2002. "Melhorando Pouco a Pouco. Manual de Sobrevivência para Sofredores de Bulimia Nervosa e outras Perturbações do Comer Excessivo.", 192 pp.. Coimbra, Portugal: Tenacitas. (Livro) Este livro de auto-ajuda oferece aos doentes de bulimia o poder de controlar as suas vidas, dando-lhes a informação e o aconselhamento necessários para resolver as suas dificuldades alimentares. De fácil leitura e ilustrado com inúmeros exemplos da vida real debruça-se sobre os problemas específicos que os doentes bulímicos têm de enfrentar diariamente. Baseando-se na investigação mais recente, e na experiência de muitos doentes, proporciona um aconselhamento detalhado, passo-a-passo, para lidar com esta situação.

Apresentação oral de trabalho Oral work presentation

1.	Macedo, A.. Investigação em Psiquiatria: O Problema da instabilidade diagnóstica,IV Encontro Associação Portuguesa de Internos de Psiquiatria,Tomar,2012 (Outra).

2.	Macedo, A.. Relação Médico-Doente em Oncologia,XXV Jornadas de Actualização em Oncologia dos HUC,Coimbra,2011 (Conferência ou palestra).

3.	Macedo, A.. Relação Médico-Doente em Oncologia,3º Simpósio de Ginecologia, Lisboa,2011 (Conferência ou palestra).

4.	Macedo, A.. O Grupo da Esquizofrenia,2º Fórum Boas práticas na Saúde Mental,Curia,2011 (Conferência ou palestra).

5.	Macedo, A.. Psiquiatria Ciências vs. Psiquiatria Arte,VII Congresso Nacional de Psiquiatria,Coimbra,2011 (Congresso).

6.	Macedo, A.. Espectro da Psicose: aspectos genéticos,Encontro de Primavera da Associação de Psiquiatria Biológica, Aveiro, 10 de Abril de 2010.,Aveiro,2010 (Conferência ou palestra).

7.

Gomes, A.A.; Tavares, J.; Bos, S.C.; Soares, M.J.; Murta, J.P.; Marques, M.; Maia, B.R.; Pereira, A.T.; Valente, J.; Cabral, A.S.; Macedo, A.; Azevedo, M.H.. Sleep, well-being, lifestyle, and academic variables: which are the main predictors of academic achievement at university?,20th Congress of the European Sleep Research Society,Lisboa,2010 (Comunicação).

8.	Macedo, A.; Pereira, A.T.; Valente, J.; Soares, M.J.; Nogueira, V.; Azevedo, M.H.. Espectro da Psicose: aspectos genéticos,1º Forum Boas Práticas na Saúde Mental,Coimbra,2010 (Conferência ou palestra).

9.	Macedo, A.; Pereira, A.T.; Valente, J.; Soares, M.J.; Nogueira, V.; Azevedo, M.H.. Genética psiquiátrica e psiquiatria.,VI Congresso Nacional de Psiquiatria,Estoril,2010 (Conferência ou palestra).

10.

Chen, X.; Lee, G.; Maher, B.S.; Fanous, A.H.; Chen, J.; Zhao, Z.; Guo, A.; Van den O. E; Sullivan, P.F.; Shi, J.; Levinson, D.F.; Gejman, P.V.; Sanders, A.; Duan, J.; Owen, M.J.; Craddock, N.J.; O’Donovan, M.C.; Blackman, J.; Lewis, D.; Kirov, G.K.; Qin, W.; Schwab, S.; Wildenauer, D.B.; Chowdari, K.; Nimgaonkar, V.; Straub, R.E.; Weinberger, D.R.; O'Neill, F.A.; Walsh, D.; Bronstein, M.; Darvasi, A.; Lencz, T.; Malhotra, A.K.; Rujescu, D.; Giegling, I.; Werge, T.; Hansen, T.; Ingason, A.; Nöethen, M.M.; Rietschel, M.; Cichon, S.; Djurovic, S.; Andreassen, O.A.; Cantor, R.M.; Ophoff, R.; Corvin, A.; Morris, D.W.; Gill, M.; Pato, C.N.; Pato, M.T.; Macedo, A.; Gurling, H.M.; McQuillin, A.; Pimm, J.; Hultman, C.M.; Lichtenstein, P.; Sklar, P.; Purcell, S.M.; Scolnick, E.M.; St Clair, D; Blackwood, D.H.; Kendler, K.S.. GWA study data-mining and independent replication identify cardiomyopathy associated 5 (CMYA5) as a risk gene for schizophrenia,XVIIIth World Congress on Psychiatric Genetics,Atenas,2010 (Conferência ou palestra). We conducted data-mining analyses using the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) and molecular genetics of schizophrenia genome-wide association study supported by the genetic association information network (MGS-GAIN) schizophrenia data sets and performed bioinformatic prioritization for all the markers with P-values p<0.05 in both data sets. In this process, we found that in the CMYA5 gene, there were two nonsynonymous markers, rs3828611 and rs10043986, showing nominal significance in both the CATIE and MGS-GAIN samples. In a combined analysis of both the CATIE and MGS-GAIN samples, rs4704591 was identified as the most significant marker in the gene. Linkage disequilibrium analyses indicated that these markers were in low LD (3 828 611–rs10043986, r2=0.008; rs10043986–rs4704591, r2=0.204). In addition, CMYA5 was reported to be physically interacting with the DTNBP1 gene, a promising candidate for schizophrenia, suggesting that CMYA5 may be involved in the same biological pathway and process. On the basis of this information, we performed replication studies for these three single-nucleotide polymorphisms. The rs3828611 was found to have conflicting results in our Irish samples and was dropped out without further investigation. The other two markers were verified in 23 other independent data sets. In a meta-analysis of all 23 replication samples (family samples, 912 families with 4160 subjects; case–control samples, 11 380 cases and 15 021 controls), we found that both markers are significantly associated with schizophrenia (rs10043986, odds ratio (OR)=1.11, 95% confidence interval (CI)=1.04–1.18, P= 8.2x10-4 and rs4704591, OR=1.07, 95% CI=1.03–1.11, P=3.0x10-4). The results were also significant for the 22 Caucasian replication samples (rs10043986, OR=1.11, 95% CI=1.03–1.17, P=0.0026 and rs4704591, OR=1.07, 95% CI=1.02–1.11, P = 0.0015). Furthermore, haplotype conditioned analyses indicated that the association signals observed (...).

11.	Macedo, A.; Soares, M.J.; Bos, S.C.; Marques, M.; Maia, B.R.; Pereira, A.T.; Gomes, A.A.; Valente, J.; Pato, M.T.; Azevedo, M.H.. Perfectionism and eating attitudes in Portuguese students: a longitudinal study.,17th EPA European Congress of Psychiatry,Lisboa,2009 (Conferência ou palestra).

12.

Macedo, A.; Marques, M.; Maia, B.R.; Soares, M.J.; Pereira, A.T.; Gomes, A.A.; Valente, J.; Bos, S.C.; Azevedo, M.H.. Conditional Acceptance as a Distinct Feature of Socially Prescribed Perfectionism: A Study in Portuguese Pregnant Women,17th EPA European Congress of Psychiatry,Lisboa,2009 (Conferência ou palestra).

13.	Macedo, A.; Marques, M.; Maia, B.R.; Soares, M.J.; Pereira, A.T.; Gomes, A.A.; Valente, J.; Bos, S.C.; Azevedo, M.H.. O que aconteceu às psicoses puerperais?,IV Jornadas de Psiquiatria dos Açores,Angra do Heroísmo,2009 (Conferência ou palestra).

14.	Pereira, A.T.; Macedo, A.; Marques, M.; Maia, B.R.; Soares, M.J.; Gomes, A.A.; Valente, J.; Bos, S.C.; Azevedo, M.H.. Será útil o rastreio da depressão perinatal?,IV Jornadas de Psiquiatria dos Açores,Angra do Heroísmo,2009 (Conferência ou palestra).

15.	Valente, J.; Macedo, A.; Marques, M.; Maia, B.R.; Soares, M.J.; Pereira, A.T.; Gomes, A.A.; Bos, S.C.; Azevedo, M.H.. Dimensão psicopatológica da menopausa,IV Jornadas de Psiquiatria dos Açores,Angra do Heroísmo,2009 (Conferência ou palestra).

16.	Macedo, A.. Genes e ambiente na Doença Afectiva,VII Simposium sobre Perturbações Afectivas,Braga,2009 (Conferência ou palestra).

17.	Cabral, A.S.; Valente, J.; Soares, M.J.; Macedo, A.; Azevedo, M.H.; Vieira, D.N.. Psychosis and Criminal Behaviour. A comparative study.,XIV World Congress of Psychiatry,Praga,2008 (Congresso).

18.	Macedo, A.; Maia, B.R.; Soares, M.J.; Pereira, A.T.; Bos, S.C.; Marques, M.; Cabral, A.S.; Valente, J.; Pocinho, F.; Azevedo, M.H.; Pato, M.T.. Obsessive-Compulsive Spectrum Disorders and Perfectionism – A study in a Portuguese Population,XIV World Congress of Psychiatry,Praga,2008 (Congresso).

19.	Macedo, A.. O continuum das psicoses: aspectos genéticos,XII Curso Anual sobre Esquizofrenia,Madrid,2007 (Simpósio).

20.	Macedo, A.. Patologia Molecular da Esquizofrenia,Conferência apresentada a a 29 de Março de 2006, no Serviço de Psiquiatria do Hospital de S. Maria, Lisboa, por convite da Directora do Serviço Profª Doutora Luísa Figueira. ,Lisboa,2006 (Conferência ou palestra).

21.	Azevedo, M.H.; Bos, S.C.; Pereira, A.T.; Maia, B.R.; Marques, M.; Soares, M.J.; Gomes, A.A.; Cabral, A.S.; Valente, J.; Macedo, A.. Stress, Insomnia and Mood States in Late Pregnancy,IV Congresso do Núcleo de Psiquiatria do Estado do Ceará,Fortaleza,2006 (Congresso).

22.	Pereira, A.T.; Soares, M.J.; Maia, B.R.; Bos, S.C.; Macedo, A.; Marques, M.; Ferreira, C.P.; Azevedo, M.H.. O Teste de Atitudes Alimentares - Versões portuguesas,XI Conferência Internacional- Avaliação Psicológica: Formas e Contextos,Braga,2006 (Comunicação).

23.	Macedo, A.. Doença bipolar e esquizofrenia – um modelo neurodesenvolvimental comum?,III Congresso de Psiquiatria e Saúde Mental dos Açores,Ponta Delgada,2006 (Congresso).

24.	Soares, M.J.; Macedo, A.; Valente, J.; Cabral, A.S.; Pato, M.T.; Pato, C.N.; Palha, J.A.; Azevedo, M.H.. Sintomas Positivos/Negativos numa amostra Portuguesa de doentes esquizofrénicos,2º Encontro sobre Esquizofrenia de Lisboa,Lisboa,2006 (Poster).

25.

Azevedo, M.H.; Soares, M.J.; Maia, B.R.; Pereira, A.T.; Gomes, A.A.; Bos, S.C.; Cabral, A.S.; Macedo, A.. Perfectionism and Sleep Disturbance in Young Males. ,18th Congress of the European Sleep Research Society,Innsbruck,2006 (Poster). Aim: To investigate the association between perfectionism and selfreported sleep disturbances in young male university students. Method: A total of 399 males (Mean age = 19.75 years, SD = 1.68) participated in the study. Hewitt & Flett (1991) Multidimensional Perfectionism Scale in its validated Portuguese version, was used to measure self-oriented (SOP), socially prescribed (SPP), and otheroriented (OOP) perfectionism dimensions. A total perfectionism score (Scale total score) is derived from the sum of scores for the individual items (n = 0 45). Two sleep items (rated from never = 0 to always = 5) covering difficulties in initiating sleep (DIS) and maintaining sleep (DMS) are used to assess sleep disturbances. An overall index of sleep disturbance (SDI) score is obtained from the sum of scores for each item. Results: Correlational analyses revealed that sleep disturbances scores were related to Scale total score and SPP, but not with SOP and OOP. On the basis of the responses to the sleep questions subjects were divided into two groups (i) Insomniacs (n = 75) consisting of subjects who experienced Difficulties initiating and / or maintaining sleep "Often /Very often and/or Always", and (ii) Good Sleepers (n = 177), including subjects who answered both sleep questions as "Never and/or Rarely". Comparing the two groups the Insomniacs had significantly higher mean scores on SPP (50.61 versus 44.14; t = )4.451; P = 0.000) and on Scale total score (194.60 versus 185.60; t = )2.331; P = 0.21). No significant differences were found on SOP and OOP. Conclusion: In this sample of male students only socially prescribed perfectionism was associated with sleep disturbances.

26.

Cabral, A.S.; Domingues, O.; Ferreira, A.M.; Macedo, A.; Azevedo, M.H.. Psychiatric Disorder and Obstructive Sleep Apnea – Preliminary Report,18th Congress of the European Sleep Research Society,Innsbruck,2006 (Poster). Obstructive Sleep Apnea (OSA) is a common and serious disorder, which affects almost every system in the body, with snoring being a frequently associated complaint. Previous studies have shown a strong association between a number of psychiatric conditions and OSA. Aim: The purpose of this work is to present preliminary results of a research to evaluate the risk factors for OSA in a population of male psychiatric patients. Methods: The study began on January 01, 2006 at the Male Psychiatric Ward of Coimbra University Hospital. Patient’s evaluation includes demographics and clinical features, daytime sleepiness (ESS, Epworth Sleepiness Scale) and anthropometric measures (Body Mass Index and neck size). Not being possible to submit all the patients to a polysomnographic study, a report of "loud snoring", "almost every day/every day", was used as an indicator of probable OSA. Result: To date 51 patients were evaluated (mean age: 40.94 years; SD: 12.347; range: 18–71). Schizophrenia (33, 3%) and Affective Disorders (33, 3%) were the predominant diagnosis. Regression analyses including age, diagnoses, body mass index, neck size, chronic neuroleptic use, chronic benzodiazepines use and alcohol abuse have shown that, among these variables, only age had a significant effect on snoring, explaining 11.5% of the total variance (R2 of all the variables was 0.248). Snoring was also shown to have no correlation with sleepiness as measured by ESS (Pearson: 0.106; P: 0.459). Conclusions: Our preliminary results suggest, as expected, that age is the most relevant risk factor of probable OSA in psychiatric patients. Sleepiness was not found to be correlated with loud snoring. Keywords: OSA, psychiatric patients, risk factors.

27.

Bos, S.C.; Pereira, A.T.; Maia, B.R.; Marques, M.; Soares, M.J.; Cabral, A.S.; Macedo, A.; Azevedo, M.H.. Self reported Insomnia and Mood States in Late Pregnancy - Preliminary report,18th Congress of the European Sleep Research Society,Innsbruck, Austria,2006 (Poster). Aim: To investigate the association between self reported insomnia and mood states in the last trimester of pregnancy. Methods: The data for this study were drawn from an ongoing cohort prospective study on Insomnia and Postpartum Depression*. To assess insomnia 6 items were applied: 3 items to evaluate insomnia symptoms and 3 items to measure insomnia daytime consequences. Mood states were assessed using the Portuguese version (Azevedo et al. 1991) of the Profile of Mood States (POMS; McNair et al., 1971) a 65- adjective Likert scale which evaluates 6 mood dimensions: Tension, Depression, Anger, Fatigue, Confusion and Vigour. Insomnia and mood states were self-reported considering the previous month. To date 60 women (mean=30.5 ± 4.8 years) were evaluated during their last trimester of pregnancy (mean=32.4 ± 3.7 weeks). Based on sleep item responses 3 groups were formed: a group with insomnia (women who referred symptoms of insomnia and daytime impairment; n = 27); a group with insomnia symptoms (n = 15) and a control group without insomnia complaints (n = 18). Mann– Whitney statistical tests were applied to compare group differences in POMS sub-scales scores. Results: The insomnia group revealed increased Tension, Depression, Anger, Fatigue, Confusion and decreased Vigour compared with both the control group (p values ranged from 0.024 for Anger to < 0.001 for Vigour) and the group with insomnia symptoms (P values ranged from 0.018 for Vigour and 0.006 for Depression). Significant differences were not observed between the group with insomnia symptoms and the control group (P > 0.05) in all POMS scales. Conclusion: Self reported insomnia in pregnant women was found to be associated with negative mood.

28.

Pereira, A.T.; Maia, B.R.; Bos, S.C.; Marques, M.; Valente, J.; Gomes, A.A.; Macedo, A.; Azevedo, M.H.. Perceived Stress and Insomnia in late Pregnancy - Preliminary report.,18th Congress of the European Sleep Research Society,Innsbruck,2006 (Poster). Aim: To investigate the association between the perception of stress and self-reported insomnia in the last trimester of pregnancy. Methods: The data for this study were drawn from an ongoing cohort prospective study on Sleep and Postpartum Depression. To assess Insomnia six items were applied: three for insomnia symptoms and three to measure interference with activities and daytime consequences. Overall perception of life stress was measured using the following item: How stressful is your life at the present time? (scored from 1 = Not stressful at all to 4 = Very stressful). Results: To date 60 women (mean = 30.5 4.8 years) were evaluated during their last trimester of pregnancy (mean=32.4 3.7 weeks). Based on sleep item responses two groups were formed: group 1 without insomnia (n = 33); and group 2 with insomnia (n = 27). Compared to the group without insomnia women with insomnia reported significantly more stress (Mann Whitney U-test = 271.500; P value = 0.010). Conclusion: In this small sample of pregnant women perceived life stress was associated with insomnia.

29.	Macedo, A.. Esquizofrenia: uma patologia da sinapse,Simpósio Da Evidência científica à prática clínica,Barcelona,2005 (Simpósio).

30.	Macedo, A.. Esquizofrenia e disfunção sináptica,Simpósio Primeiro surto de esquizofrenia,Horta/Faial,2005 (Simpósio).

31.	Bos, S.C.; Pereira, A.T.; Maia, B.R.; Soares, M.J.; Cabral, A.S.; Valente, J.; Macedo, A.; Azevedo, M.H.. Sono e Gravidez,I Congresso Nacional de Psiquiatria,Coimbra,2005 (Congresso).

32.

Palha, J.A.; Ruano, D.; Soares, M.J.; Valente, J.; Azevedo, M.H.; Goodman, A.B.; Hutz, M.H.; Gama, C.G.; Lobato, M.I.; Belmonte-de-Abreu, P.; Macedo, A.. What is linking genes and environment in schizophrenia? A potential role for thyroid hormones,Second International Colloquium of Schizophrenia, Porto, 6 a 7 de Maio de 2005.,Porto,2005 (Poster).

33.

Pereira, A.T.; Bos, S.C.; Maia, B.R.; Soares, M.J.; Cabral, A.S.; Macedo, A.; Azevedo, M.H.. The Portuguese short form of the Eating Attitudes Test-40 XXXV,XXXV Annual Congress of the European Association for Behavioural and Cognitive Therapies,Salónica,2005 (Poster). Abstract: To develop a Portuguese short form, the Eating Attitudes Test-40 (EAT-40) was administered to a community sample of 922 female students and to a clinical sample of 63 females suffering from an eating disorder. With the EAT responses of the community sample a factor analysis was performed and items with factor loadings¿=¿0.30 were selected. Internal consistency was computed for both the instrument and the factors. To study the discriminant capacity the proportion of symptomatic answers and the mean scores were compared between the clinical (N¿=¿63) and control (N¿=¿63) samples. Three factors were extracted: Drive for Thinness (14 items, a¿=¿.839), Bulimic Behaviours (8 items, a¿=¿.670), Social Pressure to Eat (3 items, a¿=¿.758). The short form is composed of 25 items and shows good internal consistency¿=¿0.839. Symptomatic answers for all items (except one) and total mean scores were significantly higher (p¿<¿.001) in the clinical sample than in community sample. Copyright © 2007 John Wiley & Sons, Ltd and Eating Disorders Association.

34.

Ruano, D.; Aulchenko, Y.S.; Macedo, A.; Soares, M.J.; Cabral, A.S.; Valente, J.; Azevedo, M.H.; Hutz, M.H.; Gama, C.G.; Lobato, M.I.; Belmonte-de-Abreu, P.; Van Belzen, M; Heutink, P.; Pato, C.N.; Palha, J.A.. Association between the Neurogranin gene and schizophrenia in males,XIIIth World Congress of Psychiatric Genetics,Boston,2005 (Poster). Introduction: The Neurogranin (NRGN) gene produces a postsynaptic brain-specific protein that regulates calmodulin/Ca2þ availability in neurons [1]. It is therefore involved in the NMDA-receptor mediated cascade, proposed to be altered in schizophrenia. NRGN expression is regulated by thyroid hormones and retinoids, which modulate the expression of various genes suggested to be implicated in schizophrenia. In addition, the NRGN gene is located at chromosome 11q24, a significant susceptibility locus in schizophrenia linkage studies [2]. Methods: We performed an association study in a Portuguese sample composed of 244 schizophrenic patients and 210 mentally healthy controls, in an independent sample composed of 73 trios from the Azores, and in a very small sample of Brazilian schizophrenic males. Results: Genotype and haplotype analysis showed association between NRGN and schizophrenia in Portuguese males. This association was confirmed by the analysis of the Azorean sample. Conclusions: Our results provide evidence that the NRGN gene is involved in the etiology of schizophrenia in Portuguese males. References: 1. Huang KP et al (2004) Neurogranin/RC3 enhances long-term potentiation and learning by promoting calcium-mediated signaling. J.Neurosci. 24 (47):10660–10669. 2. Gurling HMet al (2001) Genomewide genetic linkage analysis confirms the presence of susceptibility loci for schizophrenia, on chromosomes 1q32.2, 5q33.2, and 8p21-22 and provides support for linkage to schizophrenia, on chromosomes 11q23.3-24 and 20q12.1-11.23.

35.	Macedo, A.. Ciclofrenia: um fenótipo complexo,Simpósio “Seroquel – da evidência à prática clínica”,Barcelona,2004 (Simpósio).

36.	Macedo, A.; Azevedo, M.H.. Esquizofrenia e Farmacogenética – o fim do tratamento cego,IV Congresso da Associação de Psiquiatria Biológica “Psicofarmacologia: que futuro?”, Lisboa,2004 (Congresso).

37.

Coelho, I.M.; Dourado, A.; Valente, J.; Macedo, A.; Soares, M.J.; Pato, M.T.; Pato, C.N.; Palha, J.A.; Azevedo, M.H.. Is age at onset a useful marker for sub-typing bipolar disorder?, XIIth World Congress of Psychiatric Genetics,Dublin,2004 (Poster). To compare two groups of bipolar patients defined by age at onset of illness. Several clinical aspects were analysed including psychotic features, course, medical/psychiatric comorbidity and female reproductiven events. The sample comprises 150 Portuguese bipolar patients (92 females), aged 16–89 years (mean¼44.5, SD¼15.9), 48.7% were married, 32% single and 18.7% were divorced/separated/widowed. The data for this study were drawn from ongoing research projects on Genetic Analysis of Psychosis. Most of the patients (n¼118, 78.7%) had a family history of schizophrenia and/or affective disorder. All were interviewed using the Portuguese version of the Diagnostic Interview for Genetic Studies (DIGS) and diagnoses were based on the OPCRIT Polydiagnostic System (selected according DSM-III-R and/or CID-10n Diagnostic Criteria definitions). The age at onset was defined according to the OPCRIT definition-the earliest age at which medical advice was sought for psychiatric reasons or at which symptoms began to cause subjective distress or impair functioning—(mean¼25.05, SD¼9.25, range¼12–59). Comparing the two groups of patients (age onset<25 years, n¼86 vs.¼25 years, n¼64) no significant differences were found in most of the variables studied: birth/early development abnormal complications, family history of schizophrenia/affective disorder, substance use disorder, co-ocurrence of psychotic and affective symptoms, nicotine use, medical and psychiatric comorbidity, suicide attempts, conduct problems, rapid cycling and mixed affective states, course of disorder and female reproductive events. A significant association was found between an earlier age at onset and emotional problems during pregnancy and post-partum. However we found trends of association between lower age of onset and some of the variables above outlined. Our results are not in agreementwith those of previous studies relatively to the possibility of considering the age at onset of bipolar disorder as (...).

38.	Azevedo, M.H.; Soares, M.J.; Ferreira, A.M.; Gomes, A.A.; Bos, S.C.; Macedo, A.. Perfectionism and Sleep Disturbance in Female Students,17th Congress of the European Sleep Research Society,Praga,2004 (Poster).

39.	Soares, M.J.; Macedo, A.; Coelho, I.M.; Dourado, A.; Valente, J.; Cabral, A.S.; Pato, M.T.; Pato, C.N.; Azevedo, M.H.. Psychotic Symptoms in Bipolar Disorder,X Symposium sobre a Doença Bipolar,Cascais,2004 (Poster).

40.	Macedo, A.. Perturbações do Espectro Obsessivo-Compulsivo e Perfeccionismo,Encontro da Primavera da Associação de Psiquiatria Biológica,Lisboa,2003 (Outra).

41.	Macedo, A.; Azevedo, M.H.. Perfectionism-Related Disorders: a latent phenotype,24th International Conference Star, Lisboa,2003 (Congresso).

42.	Azevedo, M.H.; Soares, M.J.; Macedo, A.. Perfectionism and Eating Attitudes in University Students,24th International Conference Star,Lisboa,2003 (Congresso).

43.	Macedo, A.. Genética das Psicoses,II Jornadas de Psiquiatria dos Açores,Angra do Heroísmo,2003 (Outra).

44.	Macedo, A.. Kraepelin e a dicotomia das psicoses: Evidências moleculares,IX Simposium sobre a Doença Bipolar,Lisboa,2003 (Simpósio).

45.	Macedo, A.. Perfeccionismo: uma variável determinada culturalmente?,V Congresso Nacional de Psiquiatria,Lisboa,2003 (Congresso).

46.	Soares, M.J.; Macedo, A.. Perfectionism - How to Measure it,24th International Conference Star,Lisboa ,2003 (Conferência ou palestra).

47.

Pato, C.N.; Sklar, P.; Kirby, A.N.; Petryshen, T.L.; Medeiros, H.; Carvalho, C.; Macedo, A.; Dourado, A.; Coelho, I.M.; Valente, J.; Soares, M.J.; Ferreira, C.P.; Morley, C.P.; Kennedy, J.L.; Azevedo, M.H.; Lander, E.; Daly, M.J.; Pato, M.T.. Genome Wide Scan in Portuguese Island Families Identifies Likely Susceptibility Loci for Bipolar Disorder on Chromosomes 6, 11, and 19,XIth World Congress of Psychiatric Genetics,Québec,2003 (Congresso).

48.	Macedo, A.; Coelho, I.M.; Dourado, A.; Valente, J.; Soares, M.J.; Santos, V.; Azevedo, M.H.; Sklar, P.; Kennedy, J.L.; Pato, M.T.; Pato, C.N.. Genetic of Psychosis: Molecular Challenges to the Kraepelinian Dichotomy ,1º Encontro de Lisboa sobre Esquizofrenia ,Lisboa,2003 (Poster).

49.	Soares, M.J.; Gomes, A.A.; Macedo, A.; Santos, V.; Azevedo, M.H.. Multidimensional Perfectionism Scale – The Portuguese Version ,24th International Conference Star ,Lisboa ,2003 (Poster).

50.

Sklar, P.; Petryshen, T.L.; Pato, M.T.; Kirby, A.N.; Tahl, A.R.; Aldinger, K.A.; Medeiros, H.M.; Macedo, A.; Carvalho, C.; Azevedo, M.H.; Lander, E.; Daly, M.J.; Pato, C.N.. Haplotype Mapping of a Complex Disease: Schizophrenia and Chromosome 5q.,XIth World Congress of Psychiatric Genetics; Quebec, Canada, Outubro de 2003.,Quebec,2003 (Poster). Abstract: We describe the results of an aggressive, haplotype-map based screen to positionally identify a schizophrenia gene on chromosome 5q. Focusing on families of Portuguese descent collected in the Azores, Madeira and the Portuguese mainland, we identified maximum evidence of linkage (NPL¼3.1) at marker D5S820. Simulations suggested that this result was at the threshold required to declare significant genome-wide linkage, and when a handful of additional markers were added, the evidence increased to an NPL¼ 3.55. Genotyping a second smaller set of families confirmed linkage to this region. In addition, the same region of 5q was recently identified in a meta-analysis of published genome scans (importantly not including our own study) as containing a highly significant risk factor of global importance. However, as in most complex diseases, the region implicated by linkage is quite large (30 Mb) and two strategies for follow-up were pursued. We selected a set of 15 high likelihood positional and functional candidate genes for initial linkage disequilibrium mapping. SNPs were selected at a density of ~1/5kb and genotyped in 98 affected-parent trios and 150 cases and ethnically matched controls. Haplotype maps were constructed across each gene, with individual haplotypes being tested for association with schizophrenia. In the second approach, further fine mapping was undertaken by genotyping an evenly spaced SNP map across the entire 30 Mb region and the data tested for both linkage and association in the original family collection. Data from both of these strategies will be presented and all SNP data is combined to provide a first generation haplotype map of the region.

51.	Macedo, A.. Fenómenos Obsessivo-Compulsivos: do sintoma ao tratamento,Jornadas da Associação Portuguesa de Terapia do Comportamento,Coimbra,2002 (Outra).

52.	Macedo, A.; Pocinho, F.; Dourado, A.; Soares, M.J.; Pato, M.T.; Azevedo, M.H.. Perfeccionismo e Perturbações do Espectro Obsessivo-Compulsivo,Jornadas da Associação Portuguesa de Terapia do Comportamento,Coimbra,2002 (Outra).

53.	Macedo, A.. Esquizofrenia: contribuições da genética,Encontro da Primavera sobre Esquizofrenia da Associação de Psiquiatria Biológica,Porto,2002 (Outra).

54.	Macedo, A.. Genética do Envelhecimento/Genética da Doença de Alzheimer,I Encontro de Saúde Mental da Ilha Terceira,Ilha Terceira,2002 (Outra).

55.	Macedo, A.. Genética Molecular da Doença Bipolar: estado actual,IVº Simposium sobre Perturbações Afectivas,Braga,2002 (Simpósio).

56.

Pato, C.N.; Sklar, P.; Daly, M.J.; Verner, A.; Kirby, A.N.; Hudson, T.J.; Medeiros, H.M.; Morley, C.P.; Macedo, A.; Dourado, A.; Coelho, I.M.; Valente, J.; Soares, M.J.; Ferreira, C.P.; Carvalho, C.; Kennedy, J.L.; Azevedo, M.H.; Lander, E.; Pato, M.T.. Genome Scan of Schizophrenia, Bipolar Disorder and Psychosis in Portuguese families.,Xth World Congress on Psychiatric Genetics,Brussels,2002 (Congresso). Abstract: To identify genes for schizophrenia, bipolar disorder and psychosis, we have performed an initial genome-wide scan on 360 individuals from 67 multiplex Portuguese families mostly from island populations (85%). The island’s recent settlement in the 1500’s may be advantageous.We genotyped 391 markers (10 cM resolution approximately) with an average heterozygosity of 75%. Families were analyzed in three diagnostic categories: schizophrenia (DSM-IV diagnoses of schizophrenia and schiozaffective disorder depressed), bipolar disorder (DSM-IV bipolar disorder or schizoaffective manic) or psychosis (lifetime history of psychotic episode). Multipoint nonparametric linkage analysis using GENEHUNTER software was performed. In the schizophrenia families NPL scores of greater than 1.7 were obtained on chromosomes 1, 5, and 8. The regions on 1 and 5 also had NPL scores greater than 1.8 when all individuals with psychosis were considered regardless of disease phenotype. An additional chromosomal region was identified for psychosis on chromosome 11. In families with bipolar disorder, there were 6 chromosomal regions with NPL scores greater than 2.0 on chromosomes 2, 6, 9, 18, 19 and 20.We are currently fine mapping these regions in an additional 35 families to replicate previous findings and to characterize candidate genes in the region. Our observation of evidence for linkage common to schizophrenia and psychosis may indicate that genes in these regions play a role in both phenotypes, while other evidence for linkage appears to be specific for bipolar disorder and schizophrenia and not the common phenotype psychosis.

57.

Ruano, D.; Macedo, A.; Dourado, A.; Soares, M.J.; Valente, J.; Azevedo, M.H.; Coelho, I.M.; Goodman, A.B.; Palha, J.A.. Nur-related receptor 1 and schizophrenia,Xth World Congress on Psychiatric Genetics,Bruxelas,2002 (Congresso). Abstract: The human Nur-related receptor 1 (Nurr1) is an orphan nuclear receptor that can be constitutively active as a transcription factor and for which no natural ligand has yet been identified. Nurr 1 heterodimerizes with the retinoic acid 868 Abstracts receptor, RXR, and serves as a partner to facilitate vitamin A (retinoid)-regulated nuclear transcription. In the presence of proper ligands, particularly 9-cis retinoic acid, a final product of the retinoid cascade, the Nurr-1/RXR heterodimer regulates nuclear transcription of target genes. Nurr 1 is a single gene, 8.3 Kb long, consisting of eight exons that maps to chromosome 2q22-23. Several groups have reported evidence supporting a role for Nurr1 in schizophrenia: 1) Nurr1 is expressed predominantly in the dopaminergic neurons in the brain. Studies with Nurr1-null mutant mice demonstrated that Nurr1 is essential for final differentiation of ventral mesencephalic dopaminergic neurons.2) Linkage studies of schizophrenia have implicated the 2q22-23 region.3) Alterations in retinoid metabolism have been suggested to be important in the etiology of schizophrenia.4) Recently, two different missense mutations in the third exon of the Nurr 1 gene have been identified in schizophrenic patients. In the present study we investigated 165 Portuguese patients (104 men, 62 women) and 77 Portuguese controls, both diagnosed in a life-time basis using the Diagnostic Interviewfor Genetic Studies and the OPCRIT system. We failed to detect the described mutations in any of the patients or controls. For all of the above reasons it will be worthwhile to continue to search for other mutations in Nurr-1, which may increase vulnerability to schizophrenia.

58.

Flores- Villanueva, P; Palha, J.A.; McAlister, C.; Dobesova, L.M.; Belmonte-de-Abreu, P.; Ruano, D.; Macedo, A.; Dourado, A.; Soares, M.J.; Valente, J.; Azevedo, M.H.; Yunis, E.; Faraone, S.V.; Tsuang, M.T.; Goodman, A.B.. SNP of Retinoid X Receptor (RXR) at chromosome 6p21.3 associated with schizophrenia., Xth World Congress on Psychiatric Genetics,Bruxelas,2002 (Congresso). Abstract: One or another of the three RXR nuclear transcription factors act as master regulators of numerous brain-expressed genes deregulated in the schizophrenic hippocampus. RXRB lies within 1000 kb of NOTCH4. NOTCH4 is strongly associated with schizophrenia in a British sample but not in other samples, suggesting linkage disequilibrium with the causal gene.We have identified an A140T transversion in the 30 end of RXRB with significantly increased frequency among 58 treatment-resistant U. S. Caucasian schizophrenics (fSz) compared to 59 U. S. Caucasian controls (fCt). (fSz¼0.38, fCt¼0.22 P¼0.01), and among 35 African American affected sib pairs compared to 98 African controls (fSz¼0.43, fCt¼0.31 P¼0.03). Allele sharing in the sib pairs is 0.6875. The association is not confirmed in a Caucasian sample from Portugal (Sz¼200, Ct¼80), nor in a Brazilian sample (Sz¼94, Ct¼89) of unknown ethnicity. Since the polymorphism is in the 30 untranslated region of RXRB and does not alter the coding of the gene, it may influence the levels of mRNA transcripts and thus of the protein. Despite inconsistent associations, pathogenic mechanisms in the various populations may be similar, with other mutations in the RXRs affecting either protein levels or functions. RXRB genotype may be useful as a diagnostic marker or predictor of response to treatment. Our data strongly suggest that the retinoid pathway is involved in susceptibility to schizophrenia and that RXRA and RXRG may be candidate genes, as well as RXRB.

59.

Macedo, A.; Moreira, P.; Dourado, A.; Soares, M.J.; Valente, J.; Azevedo, M.H.; Coelho, I.M.; Goodman, A.B.; Saraiva, M.J.; Palha, J.A.. Searching for transthyretin polymorphisms in schizophrenia,31th Annual Meeting of the Society for Neuroscience, Orlando,2002 (Congresso). Abstract: Thyroid hormones (TH) and retinoids are essential for the normal development of the central nervous system. TH and retinoids regulate the expression of several genes, including genes of the neurotransmitter cascades. Transthyretin (TTR) is the major carrier of both TH and vitamin A in the cerebrospinal fluid (CSF). Decreased TTR levels in the CSF of patients with depression and Alzheimer’s disease have been reported, and TTR has been shown to sequester the Alzheimer’s beta-peptide. It is not known whether by itself or through the actions of its ligands TTR might be involved in the pathophysiology of behaviour disorders. The TTR gene, composed of four exons, is localized to chromosome 18q12.1. Positive lod scores at this locus have been reported for schizophrenia and bipolar disorder. In the present study we investigated 143 Portuguese Caucasian patients with schizophrenia, diagnosed in a life-time basis using the Diagnostic Interview for Genetic Studies and the OPCRIT system. We screened, by SSCP analysis, for mutations in the TTR exons 2, 3 and 4. We found 10 patients (7%) carrying the Ser 6 mutation, a polymorphism known to be present in 12% of the normal population. The absence of any other mutation suggests that alterations in the circulating protein are unlikely to be related to schizophrenia. Alterations in the regulatory regions remain as possibilities.

60.

Macedo, A.. Genética da Esquizofrenia: revisão ,Conferência apresentada a 19 de Fevereiro de 2001, na Faculdade de Medicina da Universidade Federal do Rio Grande do Sul, Portalegre, Brasil, por convite do Prof. Doutor Paulo Belmonte, responsável do Serviço de Psiquiatria.,Portalegre,2001 (Conferência ou palestra).

61.	Macedo, A.. Genética da Esquizofrenia: do fenótipo ao genótipo.,Esquizofrenia do Diagnóstico à Terapêutica,Cambridge,2001 (Simpósio).

62.

Ambrósio, A.; Macedo, A.; Valente, J.; Dourado, A.; Coelho, I.M.; Soares, M.J.; Macciardi, F.; Azevedo, M.H.; Oliveira, C.R.; Pato, M.T.; Kennedy, J.L.; Pato, C.N.. A linkage study between the GABAA Beta2 and GABAA Gama2 subunit genes and bipolar disorder,7ª Reunião da Sociedade Portuguesa de Neurociências ,Luso ,2001 (Poster).

63.	Mundo, E.; Pato, M.T.; Medeiros, H.M.; Carvalho, C.; Ferreira, C.P.; Dourado, A.; Valente, J.; Soares, M.J.; Macedo, A.; Azevedo, M.H.; Pato, C.N.. Low prevalence of schizophrenia in a homogeneous Azorean island population , IXth World Congress on Psychiatric Genetics ,Saint Louis,2001 (Poster).

64.

Xu, J.; Pato, M.T.; Torre, C.D.; Leo, R.J.; Medeiros, H.M.; Carvalho, C.; Basile, V.S.; Bauer, A.; Dourado, A.; Valente, J.; Soares, M.J.; Macedo, A.; Ferreira, C.P.; Azevedo, M.H.; Macciardi, F.; Kennedy, J.L.; Pato, C.N.. No evidence for linkage disequilibrium between the alpha 7-nicotinic receptor gene locus and bipolar disorder in the Portuguese population.,IXth World Congress on Psychiatric Genetics,Saint Louis,2001 (Congresso). Abstract: Recently we reported evidence for linkage disequilibrium and parent-of-origin effect between the alpha 7-nicotinic receptor gene (CHRNA7) locus and schizophrenia in Azorean families. The CHRNA7 is involved in the P50 sensory gating deficits. Freedman et al. had found a positive correlation between the P50 gating de®cit in schizophrenia and mania patients. We therefore proceeded to test whether the CHRNA7 genetic linkage extends beyond schizophrenia to include bipolar disorder. We genotyped markers D15S1360, D15S165 and L76630 in 19 bipolar disorder affected Portuguese families with 60 affected individuals and 62 unaffected family members. Linkage analysis by GENEHUNTER did not reveal any signi®cant associations for CHRNA7 in bipolar disorder. (...).

65.

Azevedo, M.H.; Ferreira, A.M.; Clemente, V.; Pissarra, C.M.; Gomes, A.A.; Pereira, A.T.; Silva, E.M.; Macedo, A.. Sleep Bruxism and Behvioural Disturbance in Children: a population-based study,World Conference Sleep Odyssey 2001: "Physiological Basis for Sleep Medicine",Uruguay,2001 (Conferência ou palestra).

66.	Macedo, A.; Azevedo, M.H.; Soares, M.J.; Dourado, A.; Valente, J.; Coelho, I.M.; Ambrósio, A.; Pato, M.T.; Pato, C.N.. Genética molecular das Psicoses,IIas Jornadas Insulares de Psiquiatria, Funchal,2000 (Outra).

67.	Macedo, A.. Perturbações afectivas: Genética, uma janela primordial,IIIº Simposium sobre Perturbações Afectivas "Cérebro e emoções",Braga,2000 (Simpósio).

68.	Ambrósio, A.; Kennedy, J.L.; Macciardi, F.; Muglia, P.; Vasile, V.; King, N.; Pato, C.N.; Macedo, A.; Azevedo, M.H.; Oliveira, C.R.. A hipótese glutamatérgica na Esquizofrenia,XIVa Reunião do Grupo de Estudos de Envelhecimento Cerebral e Demência,Luso,2000 (Outra).

69.	Dourado, A.; Azevedo, M.H.; Macedo, A.; Coelho, I.M.; Valente, J.; Luis, A.; Soares, M.J.; Pato, C.N.; Pato, M.T.. Reduced prevalence of psychoses in Santa Maria Island, Azores, Portugal , VIIIth World Congress on Psychiatric Genetics ,Versailles,2000 (Poster).

70.	Macedo, A.; Azevedo, M.H.; Valente, J.; Dourado, A.; Coelho, I.M.; Soares, M.J.; Pato, C.N.; Pato, M.T.. Patterns of symptoms in patients with schizophrenia ,VIII th World Congress on Psychiatric Genetics,Versailles ,2000 (Poster).

71.	Valente, J.; Azevedo, M.H.; Macedo, A.; Dourado, A.; Coelho, I.M.; Soares, M.J.; Pato, C.N.; Pato, M.T.; Kennedy, J.L.. Clinical correlates of DRD4 genotypes in patients with schizophrenia ,VIIIth World Congress on Psychiatric Genetics ,Versailles,2000 (Poster).

72.	Macedo, A.; Pocinho, F.. Hipocondria e Organização Cognitiva Obsessiva,Jornadas da Associação Portuguesa de Terapia do Comportamento,Coimbra,1999 (Outra).

73.	Macedo, A.. Esquizofrenia e Neurodesenvolvimento: um modelo explicativo,Congresso de Esquizofrenia: A Sua Problemática na Psiquiatria Moderna,Caramulo,1999 (Congresso).

74.	Azevedo, M.H.; Macedo, A.; Soares, M.J.; Dourado, A.; Valente, J.; Coelho, I.M.; Pato, M.T.; Pato, C.N.. Genética Molecular da Esquizofrenia,Congresso de Esquizofrenia: A Sua Problemática na Psiquiatria Moderna,Caramulo,1999 (Congresso).

75.	Macedo, A.. Os desenvolvimentos em Genética Psiquiátrica,III Congresso Nacional de Psiquiatria,Coimbra,1999 (Congresso).

76.	Kennedy, J.L.; Pato, M.T.; Pato, C.N.; Azevedo, M.H.; Macedo, A.; Xu, J.; Vincent, J.B.. Trinucleotide repeat analysis of Portuguese bipolar families showing anticipation ,VIIth World Congress on Psychiatric Genetics ,Monterey,1999 (Poster).

77.	Azevedo, M.H.; Macedo, A.; Soares, M.J.; Dourado, A.; Valente, J.; Coelho, I.M.; Ambrósio, A.; Pato, M.T.; Pato, C.N.. Origem da Esquizofrenia: Genética, Ambiente ou Ambos,1as Jornadas Insulares de Psiquiatria,Funchal,1998 (Outra).

78.	Macedo, A.; Azevedo, M.H.; Coelho, I.M.; Dourado, A.; Valente, J.; Soares, M.J.; Pato, M.T.; Macciardi, F.; Pato, C.N.. Genetic Anticipation in Portuguese families with Bipolar Affective Disorder ,VIth World Congress on Psychiatric Genetics,Bona,1998 (Poster).

79.	Azevedo, M.H.; Soares, M.J.; Coelho, I.M.; Dourado, A.; Valente, J.; Macedo, A.; Pato, M.T.; Pato, C.N.. Using consensus OPCRIT diagnoses: an efficient procedure for best estimate life-time diagnoses , VIth World Congress on Psychiatric Genetics,Bona,1998 (Poster).

80.	Pato, C.N.; Macedo, A.; Ambrósio, A.; Vincent, J.B.; Bauer, A.; Schindler, K.M.; Xu, J.; Coelho, I.M.; Dourado, A.; Valente, J.; Pato, M.T.; Azevedo, M.H.; Kennedy, J.L.. Detection of expansion regions in bipolar families ,VIth World Congress on Psychiatric Genetics ,Bona,1998 (Poster).

81.	Macedo, A.. Primeiro episódio da esquizofrenia: implicações genéticas, II Congresso Nacional de Psiquiatria, Coimbra,1997 (Congresso).

82.	Azevedo, M.H.; Coelho, I.M.; Macedo, A.; Valente, J.; Dourado, A.; Soares, M.J.; Ambrósio, A.; Vicente, A.; Pato, C.N.; Pato, M.T.. Estudos de Genética Molecular da Esquizofrenia e do Distúrbio Afectivo,I Congresso de Investigação em Medicina,Coimbra, Portugal,1997 (Congresso).

83.

Macedo, A.; Valente, J.; Dourado, A.; Coelho, I.M.; Vincent, J.B.; Ambrósio, A.; Sasaki, T.; Pato, C.N.; Pato, M.T.; Azevedo, M.H.; Kennedy, J.L.. Assessment for unstable DNA in schizophrenia in a Portuguese population: association with anticipation,VthWorld Congress on Psychiatric Genetics,Santa Fé,1997 (Poster).

84.

Dourado, A.; Coelho, I.M.; Macedo, A.; Valente, J.; Fourie, O.; Ambrósio, A.; Pato, C.N.; Pato, M.T.; Azevedo, M.H.; Kennedy, J.L.. Linkage and association studies of DRD3 and schizophrenia in Portuguese patients: Effect of population stratification,Vth World Congress on Psychiatric Genetics, Santa Fé,1997 (Poster).

85.	Coelho, I.M.; Macedo, A.; Valente, J.; Dourado, A.; Ambrósio, A.; King, N.; Azevedo, M.H.; Kennedy, J.L.; Pato, C.N.; Pato, M.T.. Association study of Serotonin receptors and schizophrenia in a Portuguese population,Vth World Congress on Psychiatric Genetics ,Santa Fé ,1997 (Poster).

86.

Pato, C.N.; Pato, M.T.; Faraone, S.V.; Schindler, K.M.; Coelho, I.M.; Valente, J.; Dourado, A.; Macedo, A.; Madeira, J.; Moniz, M.; Ferreira, C.P.; Azevedo, M.H.. Methodology and Statistical Power of the Portuguese Genetics of Psychosis Project,Vth World Congress on Psychiatric Genetics,Santa Fé,1997 (Poster).

87.	Valente, J.; Dourado, A.; Coelho, I.M.; Macedo, A.; Ambrósio, A.; King, N.; Kennedy, J.L.; Azevedo, M.H.; Pato, M.T.; Pato, C.N.. Association between DRD4 and schizophrenia in a Portuguese population, Vth World Congress on Psychiatric Genetics, Santa Fé ,1997 (Poster).

88.	Azevedo, M.H.; Coelho, I.M.; Macedo, A.; Valente, J.; Dourado, A.; Soares, M.J.; Ambrósio, A.; Vicente, A.; Pato, C.N.; Pato, M.T.. Estudos de Genética Molecular da Esquizofrenia , I Congresso de Investigação em Medicina,Coimbra,1997 (Poster).

89.

Vicente, A.; Ambrósio, A.; Coelho, I.M.; Macedo, A.; Valente, J.; Dourado, A.; Soares, M.J.; Pato, C.N.; Pato, M.T.; Oliveira, C.R.; Azevedo, M.H.. Estudos Genéticos da Esquizofrenia e Distúrbio Afectivo Bipolar: Análise do sistema serotoninérgico , I Congresso de Investigação em Medicina,Coimbra,1997 (Poster).

90.	Macedo, A.; Azevedo, M.H.. Antecipação Genética e Distúrbio Afectivo bipolar,II Simpósium sobre a Doença Bipolar,Sintra,1996 (Simpósio).

91.	Azevedo, M.H.; Pato, C.N.; Coelho, I.M.; Dourado, A.; Valente, J.; Macedo, A.; Pato, M.T.; Kennedy, J.L.. Pilot Association Studies with Portuguese Schizophrenics,Vth European Science Foundation MNMI Workshop,Bruxelas,1996 (Poster).

92.	Azevedo, M.H.; Pato, M.T.; Pato, C.N.; Valente, J.; Macedo, A.; Dourado, A.; Coelho, I.M.. Polydiagnostic Criteria and Genetic Research,European Regional Symposium of the World Psychiatric Association (WPA); Cascais, 10 a 14 de julho de 1994.,Cascais,1994 (Simpósio).

93.	Pato, C.N.; Azevedo, M.H.; Coelho, I.M.; Dourado, A.; Valente, J.; Macedo, A.; Ferreira, C.P.; Madeira, J.; Oliveira, C.R.; Grazina, M.; Pato, M.T.. Genetic Studies of Psychotic Disorders,II Congresso Nacional de Neurociências,Coimbra,1994 (Congresso).

94.	Macedo, A.; Azevedo, M.H.. Genética da Esquizofrenia: revisão dos contributos mais recentes.,6as Jornadas de Saúde Mental do Algarve,Carvoeiro,1994 (Outra).

95.	Azevedo, M.H.; Macedo, A.. Qualidade de Serviços em Saúde Mental ,6as Jornadas de Saúde Mental do Algarve,Carvoeiro,1994 (Outra).

96.	Macedo, A.; Azevedo, M.H.. Esquizofrenia: Evolução Nosológica e Classificações Actuais,II Congresso de Saúde Mental dos Açores,Ponta Delgada,1994 (Congresso).

97.	Macedo, A.; Kennedy, J.L.; Dourado, A.; Valente, J.; Grazina, M.; Coelho, I.M.; Pato, C.N.; Azevedo, M.H.; Pato, M.T.. Psychiatric Genetics Program at the University of Coimbra,III European Science Foundation MNMI Workshop,Kloster Seeon,1994 (Poster).

98.	Macedo, A.; Valente, J.. Quadros Psiquiátricos e Alcoolismo,Jornadas de Alcoologia da Guarda,Guarda,1993 (Outra).

99.	Dourado, A.; Macedo, A.; Pato, C.N.; Kennedy, J.L.; Valente, J.; Grazina, M.; Azevedo, M.H.; Pato, M.T.. Psychiatric Genetics Program at the University of Coimbra,II European Science Foundation MNM IWorkshop,Aussois,1993 (Poster).

100.	Azevedo, M.H.; Dourado, A.; Valente, J.; Macedo, A.; Coelho, I.M.; Pato, M.T.; Pato, C.N.. The Portuguese-Language Version of the Diagnostic Interview for Genetic Studies,IIIrd World Congress on Psychiatric Genetics,New Orleans,1993 (Poster).

Produção científica Scientific production

Produção técnica Technical production

Total

Produção científica Scientific production

185

Livros e capítulos Books and book chapters

8

Livros publicados ou organizados Published or organized books

3

Capítulos de livros publicados Published book chapters

5

Artigos científicos em revistas Papers in periodics

65

Com arbitragem científica With scientific refereeing

65

Trabalhos em eventos Papers in conference proceedings

62

Com arbitragem científica With scientific refereeing

62

Textos em jornais ou revistas Texts in journals or magazines

49

Revistas Magazines

49

Outros tipos de produção científica Other scientific production

1

Total

Produção técnica Technical production

100

Outros tipos de produção técnica Other technical production

100

	Ana Cardoso Allen Gomes
	Ana Telma Fernandes Pereira
	Berta Maria Marinho Rodrigues Maia
	Maria João de Castro Soares