Bipolar disorder is a psychiatric illness characterized by recurrent fluctuations in mood and increased risk of suicide. Twin and family studies have identified the highly heritable nature of the disorder, but the limitations of the current DNA-centric paradigm underscore the need for a new perspective to gain a clearer understanding of its basis. This project investigates various facets of bipolar disorder from an epigenetic standpoint. We used mass spectrometry-based mapping of individual DNA modification differences of the brain-derived neurotrophic factor gene. Moreover, the epigenetic basis of suicidal behaviour in bipolar disorder was investigated using DNA methylation microarrays. We also used a newly-developed enrichment technique, mTAG, to interrogate chromosome-wide DNA modification profiles using tiling microarrays in post-mortem brains of bipolar disease patients and controls. Findings from these experiments highlight observable features of epigenomes of patients affected with mood disorders, and may further the understanding of the molecular origin of psychiatric diseases.

O presente estudo avaliou um grupo de pacientes com transtorno do humor bipolar (THB), episódio depressivo, através de uma bateria de testes neuropsicológicos – Dígitos da Escala Wechsler de Inteligência para Adultos, 3ª edição (WAIS-III) e Wisconsin Card Sorting Test (WCST) –, escala de funcionalidade – Functioning Assessment Short Test (FAST) – e escala de sintomas depressivos – Montgomery-Asberg Depression Rating Scale (MADRS) – e o comparou com um grupo de controles saudáveis. Obtiveram-se como resultados déficits cognitivos significativos no grupo dos pacientes com THB, no que se refere à memória imediata e de trabalho e funções executivas, quando comparados aos controles saudáveis. Também se encontrou uma correlação entre funcionalidade, sintomatologia depressiva e déficits na memória de trabalho e funcionamento executivo. Estes achados levantam a hipótese de que as dificuldades cognitivas e sintomas depressivos interferem significativamente no funcionamento laboral, afetivo e social dos pacientes com THB. / The present study evaluated a group of patients with Bipolar Disorder (BD), major depressive episode, through a battery of neuropsychological tests - Digits of the Wechsler Intelligence Scale for Adults, 3rd edition (WAIS-III) and Wisconsin Card Sorting Test (WCST) - scale functionality - Functioning Assessment Short Test (FAST) - and scale of depressive symptoms - Montgomery-Asberg Depression Rating scale (MADRS) - and compared with a group of healthy controls. Results were obtained as significant cognitive deficits in the patients with BD, with regard to the immediate and working memory and executive functions compared to healthy controls. We also found a correlation between functionality, depressive symptoms and deficits in working memory and executive functioning. These findings raise the hypothesis that the cognitive and depressive symptoms significantly interfere with work functioning, affective and social development of BD patients.

OBJETIVOS: Avaliar associações prospectivas dos transtornos de humor e da religiosidade com o risco de suicídio em adultos jovens provenientes da população geral. MÉTODO: Coorte prospectiva de base populacional. Adultos jovens (18-24 anos) foram recrutados e acompanhados em média cinco anos depois. Risco de suicídio, transtornos de humor e de ansiedade foram avaliados usando o Mini-International Neuropsychiatric Interview. Transtornos por uso de substâncias foram avaliados utilizando o Alcohol, Smoking and Substance Involvement Screening Test. A religiosidade foi avaliada na linha de base e agrupada de acordo com a afiliação religiosa e de acordo com a freqüência de participação. RESULTADOS: A amostra incluiu 1560 adultos jovens na linha de base, com 1244 reavaliados no seguimento (80,6%). Os episódios depressivos, tanto atuais como prévios, tiveram um impacto significativo no risco de suicídio. Os episódios maníacos prévios, no entanto, foram associados com uma menor consistência a um risco de suicídio. Nenhuma associação da religiosidade com o risco de suicídio foi encontrada nas duas etapas da pesquisa. Este resultado permaneceu na análise em todas as afiliações religiosas, mesmo quando subdivididas de acordo com a freqüência de participação. CONCLUSÕES: Os episódios depressivos têm um robusto efeito prospectivo, independente, sobre o risco de suicídio. O efeito dos episódios maníacos, por outro lado, foi dependente da análise e merece uma melhor investigação. Embora existam evidências prévias sugerindo um papel protetor da religiosidade sobre o risco de suicídio, essas não foram confirmadas nessa amostra específica de adultos jovens. / OBJECTIVES: To assess the prospective associations of mood disorders, religiosity and suicidality in a community sample of young adults. METHODS: Prospective population-based cohort study. Young adults (18-24 years old) were recruited and followed-up five years later. Suicidality, mood and anxiety disorders were assessed using the Mini-International Neuropsychiatric Interview. Substance use disorders were assessed using the Alcohol, Smoking and Substance Involvement Screening Test. Religiosity were assessed at baseline and grouped according to religious affiliation and according to attendance frequency. RESULTS: The sample included 1560 young adults at baseline, with 1244 reassessed at follow-up (80.6%). Depressive episodes, both current and past had a significant impact on suicidality. Previous manic episodes, however, were less consistently associated with suicidality. No association of religiosity with suicidality was found in the two waves of the research. This effect is maintained in all religious affiliations, even when subdivided the analysis according to the frequency of attendance in religious service. CONCLUSIONS: Depressive episodes have an independent and robust effect on prospective suicidality. The effect of manic episodes, on the other hand, was dependent on the analysis and deserves further exploration. Although there is prior general evidence suggesting a protective role of religiosity on suicidality, these were not confirmed in this specific sample of young adults.

OBJETIVOS: Avaliar associações prospectivas dos transtornos de humor e da religiosidade com o risco de suicídio em adultos jovens provenientes da população geral. MÉTODO: Coorte prospectiva de base populacional. Adultos jovens (18-24 anos) foram recrutados e acompanhados em média cinco anos depois. Risco de suicídio, transtornos de humor e de ansiedade foram avaliados usando o Mini-International Neuropsychiatric Interview. Transtornos por uso de substâncias foram avaliados utilizando o Alcohol, Smoking and Substance Involvement Screening Test. A religiosidade foi avaliada na linha de base e agrupada de acordo com a afiliação religiosa e de acordo com a freqüência de participação. RESULTADOS: A amostra incluiu 1560 adultos jovens na linha de base, com 1244 reavaliados no seguimento (80,6%). Os episódios depressivos, tanto atuais como prévios, tiveram um impacto significativo no risco de suicídio. Os episódios maníacos prévios, no entanto, foram associados com uma menor consistência a um risco de suicídio. Nenhuma associação da religiosidade com o risco de suicídio foi encontrada nas duas etapas da pesquisa. Este resultado permaneceu na análise em todas as afiliações religiosas, mesmo quando subdivididas de acordo com a freqüência de participação. CONCLUSÕES: Os episódios depressivos têm um robusto efeito prospectivo, independente, sobre o risco de suicídio. O efeito dos episódios maníacos, por outro lado, foi dependente da análise e merece uma melhor investigação. Embora existam evidências prévias sugerindo um papel protetor da religiosidade sobre o risco de suicídio, essas não foram confirmadas nessa amostra específica de adultos jovens. / OBJECTIVES: To assess the prospective associations of mood disorders, religiosity and suicidality in a community sample of young adults. METHODS: Prospective population-based cohort study. Young adults (18-24 years old) were recruited and followed-up five years later. Suicidality, mood and anxiety disorders were assessed using the Mini-International Neuropsychiatric Interview. Substance use disorders were assessed using the Alcohol, Smoking and Substance Involvement Screening Test. Religiosity were assessed at baseline and grouped according to religious affiliation and according to attendance frequency. RESULTS: The sample included 1560 young adults at baseline, with 1244 reassessed at follow-up (80.6%). Depressive episodes, both current and past had a significant impact on suicidality. Previous manic episodes, however, were less consistently associated with suicidality. No association of religiosity with suicidality was found in the two waves of the research. This effect is maintained in all religious affiliations, even when subdivided the analysis according to the frequency of attendance in religious service. CONCLUSIONS: Depressive episodes have an independent and robust effect on prospective suicidality. The effect of manic episodes, on the other hand, was dependent on the analysis and deserves further exploration. Although there is prior general evidence suggesting a protective role of religiosity on suicidality, these were not confirmed in this specific sample of young adults.

O presente estudo avaliou um grupo de pacientes com transtorno do humor bipolar (THB), episódio depressivo, através de uma bateria de testes neuropsicológicos – Dígitos da Escala Wechsler de Inteligência para Adultos, 3ª edição (WAIS-III) e Wisconsin Card Sorting Test (WCST) –, escala de funcionalidade – Functioning Assessment Short Test (FAST) – e escala de sintomas depressivos – Montgomery-Asberg Depression Rating Scale (MADRS) – e o comparou com um grupo de controles saudáveis. Obtiveram-se como resultados déficits cognitivos significativos no grupo dos pacientes com THB, no que se refere à memória imediata e de trabalho e funções executivas, quando comparados aos controles saudáveis. Também se encontrou uma correlação entre funcionalidade, sintomatologia depressiva e déficits na memória de trabalho e funcionamento executivo. Estes achados levantam a hipótese de que as dificuldades cognitivas e sintomas depressivos interferem significativamente no funcionamento laboral, afetivo e social dos pacientes com THB. / The present study evaluated a group of patients with Bipolar Disorder (BD), major depressive episode, through a battery of neuropsychological tests - Digits of the Wechsler Intelligence Scale for Adults, 3rd edition (WAIS-III) and Wisconsin Card Sorting Test (WCST) - scale functionality - Functioning Assessment Short Test (FAST) - and scale of depressive symptoms - Montgomery-Asberg Depression Rating scale (MADRS) - and compared with a group of healthy controls. Results were obtained as significant cognitive deficits in the patients with BD, with regard to the immediate and working memory and executive functions compared to healthy controls. We also found a correlation between functionality, depressive symptoms and deficits in working memory and executive functioning. These findings raise the hypothesis that the cognitive and depressive symptoms significantly interfere with work functioning, affective and social development of BD patients.

O presente estudo avaliou um grupo de pacientes com transtorno do humor bipolar (THB), episódio depressivo, através de uma bateria de testes neuropsicológicos – Dígitos da Escala Wechsler de Inteligência para Adultos, 3ª edição (WAIS-III) e Wisconsin Card Sorting Test (WCST) –, escala de funcionalidade – Functioning Assessment Short Test (FAST) – e escala de sintomas depressivos – Montgomery-Asberg Depression Rating Scale (MADRS) – e o comparou com um grupo de controles saudáveis. Obtiveram-se como resultados déficits cognitivos significativos no grupo dos pacientes com THB, no que se refere à memória imediata e de trabalho e funções executivas, quando comparados aos controles saudáveis. Também se encontrou uma correlação entre funcionalidade, sintomatologia depressiva e déficits na memória de trabalho e funcionamento executivo. Estes achados levantam a hipótese de que as dificuldades cognitivas e sintomas depressivos interferem significativamente no funcionamento laboral, afetivo e social dos pacientes com THB. / The present study evaluated a group of patients with Bipolar Disorder (BD), major depressive episode, through a battery of neuropsychological tests - Digits of the Wechsler Intelligence Scale for Adults, 3rd edition (WAIS-III) and Wisconsin Card Sorting Test (WCST) - scale functionality - Functioning Assessment Short Test (FAST) - and scale of depressive symptoms - Montgomery-Asberg Depression Rating scale (MADRS) - and compared with a group of healthy controls. Results were obtained as significant cognitive deficits in the patients with BD, with regard to the immediate and working memory and executive functions compared to healthy controls. We also found a correlation between functionality, depressive symptoms and deficits in working memory and executive functioning. These findings raise the hypothesis that the cognitive and depressive symptoms significantly interfere with work functioning, affective and social development of BD patients.

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Bipolar mood disorder has been traditionally researched, explored, and explained from a modernistic, psychiatric perspective. The purpose of this study is to explicate an alternative description for bipolar mood disorder, from a postmodern perspective. The widely accepted psychiatric knowledge focuses on the signs and symptoms of the disorder, pharmacological treatments, and manualised psychotherapies. This thesis shifts the focus from an intrapsychic, deficit perspective towards one which is inclusive of surrounding discourses and patterned relationships. The social constructionist research approach is followed, utilising vignette and thematic analyses for textual deconstruction and reconstruction. In addition to these data analyses, discourses were analysed using the actual text of the co-researchers. This allowed for a thorough explication of the ways in which discourses shape the construct bipolar mood disorder. From these analyses, emergent themes were then distilled and compared to the existing body of literature in the bipolar mood spectrum field of study. Process models were generated to depict the various pertinent aspects of the social construction of bipolar mood disorder. This research has value for the treating professional, allowing for a broader, more inclusive discourse perspective to add to the already established medical model view. Further, this research gives credence to the voice of the person who has been diagnosed with the illness. This research may also contribute to the epistemological debates within modernist and postmodernist paradigms. Key words: Bipolar mood disorder, medical model, pharmacology, mania, depression, psychiatry, psychotherapy, titrating power relations, expert, problem determined systems, belonging, problems of therapy and therapeutic problems, vignette analysis, people as meaning generating beings, context, reflexivity, self-reflection, multiple realities, positivism, social constructionist epistemology, qualitative research, process model. / Psychology / D. Litt. et Phil. (Psychology)