Há poucos estudos voltados para a heterogeneidade do transtorno de déficit de atenção/hiperatividade (TDAH) em adultos, apesar de ser um transtorno psiquiátrico comum. As freqüentes associações do TDAH com outros problemas psiquiátricos aumentam a sua morbidade. Dentre essas comorbidades, destacase o transtorno depressivo maior (TDM), que além de ser freqüente influencia o impacto e a abordagem terapêutica do TDAH. Foram avaliados 320 adultos em atendimento ambulatorial para TDAH. O diagnóstico seguiu os critérios do DSM-IV. As entrevistas foram realizadas com a versão em português do K-SADS-E para TDAH e transtorno opositor desafiante (TOD), e com o SCID-IV de transtornos do eixo I para as comorbidades psiquiátricas. Os diagnósticos foram confirmados por avaliação clínica. Modelos de regressão foram aplicados para testar a associação entre a ocorrência de TDM e os desfechos clínicos e demográficos avaliados. Os indivíduos com TDAH e TDM apresentaram maior freqüência de diagnóstico de transtornos de ansiedade e experiência de tratamento prévio (tanto psicoterápico quanto farmacológico) quando comparados a indivíduos com TDAH, sem TDM. Por outro lado, apresentaram menos freqüentemente diagnóstico de dependência de drogas e histórico escolar de repetência ou suspensões de classe. Não houve diferença significativa entre os grupos com ou sem TDM quanto à idade do diagnóstico de TDAH. Os achados sugerem uma utilidade do diagnóstico de TDM como um indicador relevante de determinadas características clínicas em adultos com TDAH. A maior procura por tratamento relacionada ao TDM não foi acompanhada de um diagnóstico mais precoce do TDAH, como seria esperado. Se confirmados, esses dados apontam para a necessidade de pesquisas e educação médica voltadas para um reconhecimento mais eficiente e precoce do TDAH em pacientes que buscam atendimento em saúde mental por outras causas. / There are few studies on the heterogeneity of adult ADHD, despite it is a common psychiatric disorder. The frequent comorbidity between ADHD and other psychiatric problems, increases the morbidity of the disorder. Major depressive disorder (MDD) stands out between other ADHD comorbidities, since it is frequent and influences ADHD outcomes and therapeutic approach. Three hundred and twenty adult outpatients were evaluated for ADHD. Diagnosis followed DSM-IV criteria. Interviews to evaluate ADHD and oppositional defiant disorder (ODD) were performed based on the Portuguese-language version of K-SADS-E and Psychiatric comorbidities were evaluated using SCID-IV for axis I disorders. Diagnoses were confirmed by clinical interview. Regression models were applied to test MDD association with clinical and demographic outcomes. Subjects presenting ADHD and MDD had a higher frequency of anxiety diagnosis and prior experience of psychotherapy and/or pharmacological treatment when compared to ADHD subjects free of MDD. On the other hand, they reported less often drug dependence diagnosis, grade repetition and school suspensions. There was no significant difference between groups with or without MDD on the age at ADHD diagnosis. These findings suggest that the MDD diagnosis may be useful as an important indicator of certain clinical characteristics in adults with ADHD. The more frequent search for treatment attributable to MDD diagnosis was not accompanied by an earlier ADHD diagnosis, as expected. If confirmed, the present data point to the need for research and medical education towards an earlier and more efficient ADHD diagnosis in patients who search for mental health care for other reasons.

The teaching profession is responsible for training professionals from various fields of knowledge; however, exercising the magisterium is an old function and problems generated also have followed it. In this sense, the accumulation and variety of its functions can trigger overload and make them susceptible to work-related stress, identified as a risk factor for depression. In this aspect, the practice of health care teachers are doubly subject to emotional distress situations, since it is generated by the need that the teacher has to be caregiver during the process of teaching and learning. Depression is a syndrome characterized by mood swings that still compromises the quality of life (QoL). The overall objective of the study was to assess the QoL and depression in teaching in the area of Health in the São Cristóvão Campus at UFS. This is a descriptive, cross-sectional study, with a quantitative approach. The convenience sample consisted of 146 teachers. We used three data collection instruments, the Whoqol-Bref, Beck Depression Inventory and a sociodemographic questionnaire prepared by the researchers. The collecting took place from February to November 2015. The data were analyzed descriptively and analytically. The results show that 58.2% of respondents are female, with a mean age of 44.44 years old, 54.8% Caucasian, 63% married, 56.16% doctors, 52.05% full-time commitment, 70.5% dissatisfied with working conditions, 78.8% dissatisfied with pay, 68.5% practice physical activity and 98% practice leisure activities. The results of two general questions of the Whoqol-Bref showed that most of the teachers have positive perception of their QoL (84.9%) and were satisfied with their health (67.8%). The prevalence of teachers with depression was 29.5%. It was concluded that the teachers presented, on a larger scale, satisfaction with their QoL and health. However, the prevalence of depression was high and was associated with QoL, dissatisfaction of working conditions and leisure activities. Therefore, it suggests that depression can have a negative effect on the QoL of individuals, dissatisfaction with working conditions may be associated the development or worsening of disease, in against departure, the results point to a possible protective effect of leisure activities offer mental health. / A docência superior é responsável pela formação de profissionais das diversas áreas do conhecimento, no entanto, exercer o magistério é uma função antiga e os problemas gerados também a acompanham. Nesse sentido, o acúmulo e variedade de suas funções podem desencadear sobrecarga e torná-los susceptíveis ao estresse laboral, apontado como fator de risco para depressão. Nessa vertente, a prática dos docentes da área da saúde está duplamente sujeita a situações de desgaste, visto que ele é gerado pela necessidade que o docente tem em ser cuidador durante o processo de ensino aprendizagem. A depressão é uma síndrome caracterizada por alterações do humor que compromete ainda a qualidade de vida (QV). O objetivo geral do estudo foi Avaliar a QV e depressão em docentes da área da Saúde do Campus São Cristóvão da UFS. Trata-se de um estudo descritivo, de corte transversal, com abordagem quantitativa. A amostra por conveniência foi composta por 146 docentes. Foram utilizados três instrumentos de coleta de dados, o Whoqol-Bref, o inventário de depressão de Beck e um questionário sociodemográfico elaborado pelos pesquisadores. A coleta ocorreu no período de fevereiro a novembro de 2015. Os dados foram analisados de forma descritiva e analítica. Os resultados demonstram que 58,2% dos pesquisados são do gênero feminino, com média de idade de 44,44 anos, 54,8% da raça branca, 63% casados, 56,16% doutores, 52,05% dedicação exclusiva, 70,5% insatisfeitos com as condições de trabalho, 78,8% insatisfeitos com remuneração salarial, 68,5% praticam atividade física e 98% praticam atividades de lazer. Os resultados das duas questões gerais do Whoqol-Bref mostraram que a maior parte dos docentes têm percepção positiva da sua QV (84,9%) e estavam satisfeitos com sua saúde (67,8%). A prevalência de docentes com depressão foi de 29,5%. Foi possível concluir que, os docentes apresentaram em maior escala satisfação com sua QV e saúde. No entanto, a prevalência de depressão foi alta e houve associação com a QV, insatisfação das condições de trabalho e atividades de lazer, portanto, sugere que a depressão pode interferir negativamente na QV dos indivíduos, a insatisfação com as condições de trabalho pode estar associada ao desenvolvimento ou agravamento da doença, em contra partida, os resultados apontam para um possível efeito protetor que as atividades de lazer oferecem a saúde mental. / Lagarto, SE

Orientador : Fernanda Klein Marcondes / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-16T20:04:06Z (GMT). No. of bitstreams: 1 Kurihara_Eduardo_D.pdf: 8662051 bytes, checksum: 2fecc7c63194c2b9417a7f37f2a3a380 (MD5) Previous issue date: 2010 / Resumo: O envelhecimento resulta em transformações fisiológicas que podem comprometer a homeostasia bucal. Eventos estressantes, desordens psicológicas, sintomatologia depressiva ou o próprio lugar onde se vive são fatores que podem influenciar, direta ou indiretamente, a saúde bucal do indivíduo. O fenômeno do envelhecimento leva a redução na higiene bucal e ao aumento de doenças bucais em idosos, especialmente em idosos institucionalizados, que muitas vezes apresentam um estilo de vida solitário. Historicamente o Brasil carece de políticas públicas voltadas para a saúde bucal do idoso e conta com poucas informações sobre o número de idosos que vivem em instituições asilares e sobre as reais condições em que eles vivem. Portanto, o objetivo deste estudo foi comparar as condições de saúde bucal entre idosos institucionalizados e não institucionalizados na cidade de Maringá - PR, e analisar como as variáveis clínicas e/ou subjetivas se correlacionam. As condições subjetivas de saúde bucal foram avaliadas por meio do índice General Oral Health Assessment Index (GOHAI). A condição psicológica foi avaliada pela Escala de Depressão Geriátrica (GDS-15) e a autopercepção de situações estressantes pela Escala de Estresse Percebido (PSS). A avaliação clínica da saúde bucal foi feita por meio do índice de dentes cariados, perdidos, obturados (CPO-D) e por meio da análise de uso e necessidade de próteses removíveis. O fluxo de saliva e o nível de cortisol salivar foram medidos. Os resultados mostraram que o grupo institucionalizado apresentou mais sintomas depressivos, menor fluxo salivar, maior número de dentes perdidos e cariados, e apresentou também maior freqüência de uso e necessidade de próteses dentárias em comparação com o grupo não institucionalizado. Idosos não institucionalizados apresentaram maior quantidade de dentes restaurados. Foram observadas correlações entre fluxo salivar e necessidade de próteses, e entre fluxo salivar e dentes cariados. GOHAI, PSS e níveis de cortisol salivar não diferiram entre os grupos. Este estudo revelou uma precária condição de saúde bucal e sintomas depressivos nos indivíduos institucionalizados em relação aos não institucionalizados, sugerindo a necessidade de mais estudos para investigar a saúde bucal de idosos institucionalizados para fornecer-lhes cuidados mais adequados de higiene bucal através de programas educacionais, preventivos e curativos. / Abstract: Aging results in physiological changes which might affect oral homeostasis. Stressful events, psychological disorders, depressive symptoms or dwellings are factors that might have a direct or indirect influence on the individual's oral health. The aging phenomenon leads to a reduction in oral hygiene and an increase in dental diseases in the elderly, especially the institutionalized ones who, in most cases, have quite a dependent and/or lonely lifestyle. Historically, Brazilian policies concerning public oral health for the elderly are poor and little information about the number of institutionalized elderlies and their lifestyle is provided. Therefore, the aim of this study was to compare the oral health status between institutionalized and non-institutionalized elderlies living in Maringá, PR, Brazil and to assess how clinical and subjective variables are correlated. Subjective oral health conditions based on the General Health Assessment Index (GOHAI) were analyzed. The Geriatric Depression Scale (GDS-15) and Perceived Stress Scale (PSS) were used to evaluate the psychological conditions and the stress self-perception of all individuals, respectively. The dental status of the subjects was evaluated using the decayed, missing, filled teeth index (DMFT) considering their use or need for removable dental prostheses. The salivary flow and salivary cortisol levels were measured. Results showed that the institutionalized subjects had more depressive symptoms, lower salivary flow and a larger number of missing and decayed teeth when compared to the non-institutionalized individuals, having a larger number of filled teeth. The use and need for prosthesis were more prevalent in the institutionalized group. Correlation was found between salivary flow and need for prosthesis, and between salivary flow and missing teeth. No statistically significant difference was found among GOHAI, PSS and salivary cortisol levels. This study revealed a poorer oral health status and depressive symptoms for the institutionalized individuals, suggesting that further studies are needed to investigate oral health in institutionalized elderly providing them with adequate dental care and information on oral hygiene through educational, preventive and curative programs. / Doutorado / Fisiologia Oral / Doutor em Odontologia

O Transtorno da Depressão Maior (MDD) é uma doença muito difundida em todo mundo e com uma alta prevalência, principalmente em mulheres. Transtornos de humor são recorrentes e ameaçam a vida, devido ao risco de suicídio. Apesar disso, a etiologia do MDD ainda é pouco entendida e diversas hipóteses foram desenvolvidas na tentativa de explicá-la. Uma delas está ligada ao estresse. Distúrbios no eixo hipotálamo-hipófiseadrenal (HPA) estão presentes em cerca 70% de pacientes com depressão. Ao buscar um melhor modelo animal para estudo do impacto do estresse no desenvolvimento da depressão, chegamos ao estresse leve crônico (CMS). Em estudos prévios desenvolvidos neste laboratório, observamos que há diferenças entre tipos de estressores e os mediadores secretados na resposta do eixo HPA, isto é, durante o estresse físico é secretado o mediador vasopressina, enquanto que no estresse psicológico, é secretado o mediador CRF; já nos estresses considerados mistos (como nado forçado), ambos os mediadores estão presentes. Assim, propusemos estabelecer protocolos de CMS baseados no protocolo original de Paul Willner, pesquisador que desenvolveu este modelo, empregando estressores do tipo físico ou psicológico, separadamente. O que observamos foi que nenhum dos dois tipos de estressores conseguiu levar os animais à anedonia (queda na preferência por sacarose). No entanto, ao observar o ganho de peso dos animais ao longo do tempo e o mapeamento cerebral com citocromo c oxidase, notamos que o estresse teve seu impacto no animais. Comparados a outros modelos de depressão, o CMS tem a premissa de desenvolver um estado depressivo nos animais antes do teste com drogas antidepressivas, fazendo com que tenha uma alta validade preditiva. Ele também pode incorporar outros endpoints para avaliar outros comportamentos, além da anedonia, que possam demonstrar o estado depressivo no animal. Por exemplo, observamos no mapeamento cerebral que a substância negra e a PAG estiveram mais ativas no estresse físico e elas podem estar implicadas na busca por recompensa e na modulação de dor, respectivamente. Concluímos que o modelo de CMS é apropriado, embora ainda necessite de estudos quanto à equivalência de intensidade de estressores / Major Depressive Disorder (MDD) is a widespread disease all over the world with a high prevalence, especially among women. Mood disorders are recurrent and life threatening, due to suicide risk. Despite those, MDD etiology is poorly understood and several hypotheses have been developed to try and explain it. One of them is connected to stress. Disorders on the hypothalamus-pituitary-adrenal (HPA) axis are present in up to 70% of patients with depression. While searching for a better animal model to study the impact that stress might have on depression onset, we came across the Chronic Mild Stress (CMS) model. During previous studies developed in this lab, weve observed that there are differences between types of stressors and mediators involved in the HPA axis response, i.e. during physical stress, the mediator secreted is vasopressin, whereas during psychological stress, the mediator is CRF; on mixed stress (like forced swim), both mediators are present. That way, we proposed to set up CMS protocols based on Paul Willner (the researcher who developed this model)s original one, employing physical or psychological stressors separately. None of the types of stressors were able to induce anhedonia (decrease in sucrose preference) in the animals. However, noticing the animals weight gain over time, and cerebral mapping with cytochrome c oxidase, we could see that stress had impact over the animals. Compared to other depression models, CMS has the presupposition of leading the animals to a depressive-like state before testing antidepressant drugs, which gives it a high predictive validity. The model can also incorporate different endpoints to assess other behaviors, besides anhedonia, that may show the animals depressive-like state. For instance, we observed in the brain mapping that substantia nigra and PAG were more activated in physical stress and they can be implicated in reward seeking and pain modulation, respectively. So, we conclude that the CMS model is appropriate, although it still needs more research regarding the intensity of stressors equivalence

Orientador: Maria Elena Guariento / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-19T14:37:19Z (GMT). No. of bitstreams: 1 Bombardi_MarceloFrancisco_M.pdf: 962184 bytes, checksum: b523e5e6519b7a38484ecdc37b4cb53a (MD5) Previous issue date: 2012 / Resumo: Inúmeros pesquisadores, órgãos públicos e governos discutem, hoje, o envelhecimento da população mundial, bem como as mudanças no âmbito de saúde pública e de organização social, relacionadas a esse fenômeno demográfico. O novo panorama social que vem se instalando promete transformações bastante significativas, principalmente na esfera da atenção à saúde. A população idosa é a que mais necessita de cuidados de saúde, pois tem mais fatores de risco para doenças e agravos crônicos que outras faixas etárias. Assim, é importante traçar o perfil de funcionalidade do paciente idoso, para poder elaborar e implementar estratégias eficientes, tanto em nível da terapêutica como da prevenção de agravos, de forma a diminuir ou controlar o risco de dependência decorrente de déficit funcional, cognitivo, ou relacionado a transtornos depressivos. O presente projeto buscou mostrar o perfil funcional, cognitivo e de estado de humor de uma amostra de idosos assistidos no Ambulatório de Geriatria do Hospital das Clínicas da Universidade Estadual de Campinas, São Paulo, Brasil (AG/HC-Unicamp). Assim foram coletados os dados de prontuários de pacientes seguidos no AG/HC -Unicamp no período de 2005 a 2007. Para tal pesquisa, foi criado um instrumento para registro de dados que abrangiam as variáveis: capacidade funcional, capacidade cognitiva e sintomas depressivos. Foram avaliados os dados de 98 prontuários médicos verificou-se predominância no sexo feminino em ambas faixas etárias de 70 a 79 anos (40%) e maior ou igual a 80 anos (40%). Fazendo-se a análise dos resultados verificou-se diferença significativa entre os gêneros para número de funções comprometidas em Atividades de Vida Diária (AVD) (p=0,014) e Atividades Instrumentais de Vida Diária (AIVD) (p<0,001). Porém quando se considerou o número de comorbidades, evidenciou-se associação significativa com pontuação abaixo da nota de corte no MEEM. Observou-se também que 88% da amostra se encontrava na faixa de escolaridade de zero a quatro anos. Entre os resultados, verificou-se que 33% dos idosos apresentavam pelo menos uma função comprometida em AVD e 52% apresentavam pelo menos uma função comprometida em AIVD. Os idosos com 80 anos e mais apresentaram mais funções comprometidas em AIVD. Já com relação ao desempenho cognitivo, 58,70% apresentavam algum grau de déficit avaliado pelo MEEM. Com relação às doenças, os três sistemas mais acometidos segundo as categorias adotadas pela Classificação Internacional de Doenças (CID-10) foram as seguintes: 1) doenças cardiovasculares (29,7%); 2) doenças endócrinas, nutricionais e metabólicas (17,2%) e 3) doenças osteomusculares e do tecido conjuntivo (13%). Com relação ao consumo regular de medicamentos, esse foi maior na faixa etária de 60 a 79 anos. Constatou-se, finalmente que os idosos com funcionalidade mais comprometida eram: as mulheres, os mais idosos, os que tinham maior número de comorbidade, os que tinham IMC acima da faixa de normalidade, os que tinham maior estatura e os que usavam mais fármacos regularmente / Abstract: Several researchers, public agencies and governments discuss nowadays, the world population aging, as well as changes in the public health system and social organization, related to this demographic phenomenon. The new social scene that has been installed promises many significant changes, especially in the health care situation. The elderly population is the one who most needs health care, because of the incidence of more risk factors for chronic diseases and health problems than the other age groups. Thus, it is important to profile the elderly patients functionality, in order to develop and implement effective strategies, both in terms of therapy as in the prevention of serious diseases in order to reduce or control the risk of dependence due to functional deficit, cognitive, or related to depressive disorders. This project researched and decided to show the functional profile, cognitive and mood of a sample of senior citizens of the Clinic Hospital of the State, Brazil. Thus the data were collected from medical records of patients followed at the patient Clinic of Geriatrics, from the clinic Hospital of the State University of Campinas in the period from 2005 to 2007. For this study, we created a data collection instrument that included the variables: functional, cognitive capacities and depressive symptoms. We evaluated data from 98 medical records. There was predominance of female patients in both age groups 70 to 79 years old (40%) and greater than or equal to 80 years old (40%). Making the analysis of the results a significant difference was found between genders for the numbers of functions impaired in ADL (p=0.014) and IADL (p<0.001). However when it was considered the the number of comorbidities, it showed a significant association with scores below the cutoff score on the Mini Mental. It was also observed that 88% of the sample was in the range of schooling from zero to four years. Among the results, it was found that 33% of the senior citizens had at least one function impaired in ADLs and 52% had committed at least one function in IADL. The elderly people aged 80 and over this age were more impaired in IADL functions. Regarding the cognitive performance, 58,70% had some degree of deficit assessed by the Mini Mental. Refering to the three most affected systems to the categories adopted by the International Classification of Diseases (ICD-10) were as follows: 1) cardiovascular diseases (29,7%), 2) endocrine, nutritional and metabolic diseases (17,2%) and 3) musculoskeletal and connective tissue diseases (13%). Regarding to the regular consumption of drugs, this was higher in the age group 60 to 79 years old. It was found finally that the elderly that had more committed functionality were: women, the oldest ones, and those who had more comorbidity problems, and those who had a BMI above the normal range, those with greater height and those who used more drugs regularly / Mestrado / Gerontologia / Mestre em Gerontologia

Only one third of depressed patients experience a beneficial therapeutic effect after using a first-line medication, leaving two-thirds of patients without effective treatment. It has been shown that a combination of two drugs with different modes of action result in an increase in the number of patients responding to treatment. One of the most effective strategies is the addition of low doses of an atypical antipsychotic. In depth evaluation of the neurobiological properties of atypical antipsychotics have revealed that these agents produce antidepressant effects and enhance the therapeutic response of first-line medications through antagonism of the 5-HT2A, 5-HT2C, 5-HT1B/D, 5-HT7 receptors and NET; agonism of the 5-HT1A receptor; and/or D2/3 partial agonism. The present experiments focused on determining the mode of action of this combination of drugs to help design better antidepressant treatment in the future. A series of electrophysiological experiments were proposed to assess 5-HT and NE neurotransmission in the rat hippocampus, as well as DA transmission in the rat forebrain.

Syfte: Depression är en av våra vanligaste folksjukdomar. Studier visar att fysisk aktivitet ger likvärdig positiv effekt som annan behandling. Syftet med studien var att undersöka och beskriva upplevelser och erfarenheter av fysisk aktivitet och träning samt underlättande och hindrande faktorer hos personer med depression   Design och metod: Kvalitativ, explorativ och deskriptiv design. Fem semistrukturerade intervjuer utfördes. En kvalitativ innehållsanalys användes.   Resultat: För att presentera den data som insamlats i intervjuerna formulerades sex kategorier med 23 underkategorier. Resultaten tyder på såväl kortsiktiga som långsiktiga positiva upplevelser under och efter träning. Det visade även på upplevda hindrande och underlättande faktorer för att påbörja och vidmakthålla träningsvanor. Exempelvis kunde socialt stöd, uppföljning, struktur och träningsvana fungera underlättande. Försvårande faktorer var exempelvis stresskänslighet och depressionens inverkan. Slutligen framkom potentiella förbättringsmöjligheter inom hälso- och sjukvård, såsom mer frekventa träningstillfällen.    Konklusion: Fysisk aktivitet påverkar det upplevda måendet positivt för informanterna i studien. Det finns faktorer som underlättar och försvårar möjligheten att vara fysiskt aktiv. Studien tyder på att det går att förbättra nuvarande behandlingar med bland annat mer kontinuitet och frekventa träningstillfällen samt socialt stöd och uppföljning. En förhoppning är att studien kan bidra med ytterligare kunskap om vad som behövs för att öka möjligheten för personer med depression att kunna ta del av fysisk aktivitet som en behandlingsmöjlighet. / Purpose: Depression is one of the most common diseases in modern time. Studies show that physical activity has equivalent effect on the condition as compared to other treatments. The purpose of the study was to investigate how physical activity and exercise is experienced by people suffering from depression.   Design and method: Qualitative design, descriptive and explorative. Five semi-structured interviews. Qualitative content analysis was conducted.   Results: To present interview data, six categories with 23 subsequent subcategories were identified. Results indicate short and long term positive experiences during and after exercise. Facilitating and hindering factors regarding initiating and maintaining exercise habits were also shown.  Facilitating factors included social support, structure, previous exercise habits and monitoring. Hindering factors included sensitivity to stress and the disease itself. Finally, potential improvement possibilities within healthcare emerged, such as greater frequency of exercise occasions offered.   Conclusion: Physical activity had a positive effect on the well-being of the informants. There are facilitating and hindering factors to being physically active while depressed. The study shows potential improvements that could be made to current healthcare procedures such as greater continuity and frequency of exercise opportunities, as well as social support and monitoring. Hopefully this study can provide further knowledge of the factors needed to facilitate people suffering from depression taking part in physical activity as treatment for the condition.

Bipolar disorder (BD) and major depressive disorder (MDD) are characterised by a fundamental disturbance of mood, with strong support for overlapping causal pathways. Structural brain and neurocognitive abnormalities have been associated with mood disorders, but it is unknown whether these reflect early adverse effects predisposing to mood disorders or emerge as a consequence of illness onset. The Bipolar Family Study is well-suited to examine the origin of structural brain and neuropsychological abnormalities in mood disorders further. The volumes of subcortical brain regions, cortical thickness and surface area measures of frontal and temporal regions of interest and neuropsychological performance over a two-year time interval was compared at baseline and longitudinally between three groups: young individuals at high risk of mood disorders who subsequently developed MDD during the follow-up period (HR-MDD), individuals at high risk of mood disorders who remained well (HR-well), and healthy control subjects (HC). The longitudinal analysis of cortical thickness revealed significant group effects for the right parahippocampal and right fusiform gyrus. Cortical thickness in both of these brain regions across the two time points was reduced in both high-risk groups relative to controls, with the HR-MDD group displaying a thinner parahippocampus gyrus than the HR-well group. Moreover, a significant interaction effect was observed for the left inferior frontal and left precentral gyrus. The HR-well subjects had progressive thickness reductions in these brain regions relative to controls, while the HR-MDD group showed cortical thickening of these areas. Finally, longitudinal analyses of neuropsychological performance revealed a significant group effect for long delay verbal memory and extradimensional set-shifting performance. Reduced neurocognitive performance during both tasks across the two time points was found in the HR-well group relative to controls, with the HR-MDD group displaying decreased extradimensional set-shifting abilities as compared to the HC group only. These findings indicate, that reduced left parahippocampal and fusiform thickness constitute a familial trait marker for vulnerability to mood disorders and may thus form potential neuroanatomic endophenotypes. Particularly strong thickness reductions of the parahippocampal gyrus appear be linked to an onset of MDD. Moreover, progressive thickness reductions in the left inferior frontal and precentral gyrus in early adulthood form a familial trait marker for vulnerability to mood disorders, potentially reflecting early neurodegenerative processes. By contrast, an absence of cortical thinning of these brain regions in early adulthood appears to be linked to the onset of MDD, potentially reflecting a lack or delay of normal synaptic pruning processes. Reduced long delay verbal memory and extradimensional set-shifting performance across time constitute a familial trait marker for vulnerability to mood disorders, likely representing disturbances of normal brain development predisposing to illness. These findings advance our understanding of the origin of structural brain and neurocognitive abnormalities in mood disorders.

Certain electrophysiological markers hold promise in distinguishing individuals with major depressive disorder (MDD) and in predicting antidepressant response, thereby assisting with assessment and optimizing treatment, respectively. This thesis examined resting brain activity via electroencephalographic (EEG) recordings, as well as EEG-derived event-related potentials (ERPs) to auditory stimuli and facial expression presentations in individuals with MDD and controls. Additionally, the utility of resting EEG as well as auditory ERPs (AEPs), and the associated loudness-dependence of AEPs (LDAEP) slope, were assessed in predicating outcome to chronic treatment with one of three antidepressant regimens [escitalopram (ESC); bupropion (BUP); ESC+BUP]. Relative to controls, depressed adults had lower pretreatment cortical activity in regions implicated in approach motives/positive processing. Increased anterior cingulate cortex (ACC)-localized theta was observed, possibly reflecting emotion/cognitive regulation disturbances in the disorder. AEPs and LDAEPs, putative indices of serotonin activity (implicated in MDD etiology), were largely unaltered in MDD. Assessment of ERPs to facial expression processing indicated slightly blunted late preconscious perceptual processing of expressions, and prolonged processing of intensely sad faces in MDD. Faces were rated as sadder overall in MDD, indicating a negative processing bias. Treatment responders (vs. non-responders) exhibited baseline cortical hypoactivity; after a week of treatment, cortical arousal emerged in responders. Increased baseline left fronto-cortical activity and early shifts towards this profile were noted in responders (vs. non-responders). Responders exhibited a steep, and non-responders shallow, baseline N1 LDAEP derived from primary auditory cortex activity. P2 LDAEP slopes (primary auditory cortex-derived) increased after a week of treatment in responders and decreased in non-responders. Consistent with overall findings, ESC responders displayed baseline cortical hypoactivity and steep LDAEP-sLORETA slopes (vs. non-responders). BUP responders also exhibited steep baseline slopes and high ACC theta. These results indicate that specific resting brain activity profiles appear to distinguish depressed from non-depressed individuals. Subtle ERP modulations to simple auditory and emotive processing also existed in MDD. Resting alpha power, ACC theta activity and LDAEP slopes predicted antidepressant response in general, but were limited in predicting outcome to a particular treatment, which may be associated with limited sample sizes.

Previous magnetic resonance imaging (MRI) studies have demonstrated brain atrophy in major depressive disorder (MDD) that is progressive with continuing illness and may be reversible with antidepressant treatment. What remains unclear is whether brain structure can be positively affected by pharmacological intervention even if patients fail to remit on the treatment. The primary aim of this thesis was to prospectively track changes in brain structure in patients with treatment-resistant depression while they underwent pharmacotherapy with the goal of attaining remission. There is evidence that gene variants associated with poorer antidepressant response also confer greater risk of volume reduction in the hippocampus. A secondary aim of the thesis was to investigate the effects of monoaminergic-related gene variants on hippocampal volume in patients and controls at baseline imaging. Outpatients with treatment-resistant MDD underwent structural MRI scans at baseline and after either 6-months of sustained remission or 12-months of failure to remit. Matched controls were scanned once to provide comparison data for patients’ baseline scans. Participants also provided blood samples for genetic analyses. Imaging outcome measures included longitudinal changes in whole-brain volume, and gray matter volume and mean cortical thickness within specific cortico-limbic regions of interest (ROIs). Over follow-up, remitted patients had an increase in whole-brain volume, while nonremitted patients lost brain volume despite receiving more treatment strategies. Remitters and nonremitters also showed subtle changes in volume and thickness over time in several ROIs in opposing directions, with increasing hippocampal volume and cortical thickness in the rostral middle frontal gyrus and orbitofrontal cortex in remitters, and decreasing volume or thickness in these regions in nonremitters. Genetic imaging analyses revealed that polymorphisms in certain norepinephrine- and serotonin-related genes have similar effects on hippocampal volume in patients and controls, while the serotonin transporter polymorphism differentially affects hippocampal volume in the presence of depression. Given the observations of volume increase in remitted patients and continuing atrophy in nonremitters, pharmacotherapy in the absence of sustained remission is likely insufficient to elicit structural recovery in depression. This finding is important since the restoration of brain structure in patients with treatment-resistant depression may have positive implications for their future prognosis.