Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2010.

No description available.

Resting frontal electroencephalographic (EEG) asymmetry has been hypothesized to be a biological marker of clinical depression but may reflect an endophenotype specific to women. Frontal EEG asymmetry was assessed in individuals (22% male) with (n = 12) and without (n = 21) a DSM-IV diagnosis of lifetime Major Depressive Disorder (MDD) or Dysthmic Disorder on 4 occasions within a two-week period. Depressed women exhibited greater relative right frontal activity at rest than never-depressed women across occasions. In contrast, depressed men displayed greater relative left frontal activity than never-depressed men. The same participants engaged in a Passive Viewing Face task while undergoing functional magnetic resonance imaging (fMRI). The present study did not replicate previous findings which show a hyperactive hemodynamic response in the amygdalae among depressed individuals. Mixed linear models indicated a lifetime depression by biological sex by amygdala activation interaction. For never-depressed control participants, frontal asymmetry is unrelated to the level of emotion-related amygdalae activation, but for lifetime depression spectrum participants, in both men and women, relatively greater amygdalae activation to emotional faces is associated with less left frontal activity as compared to those with less amygdalae activation to emotional faces. Also, when activation to emotionally expressive faces was closer to the levels of activation observed in the neutral face condition, the predicted pattern of association between frontal EEG asymmetry and depression based on the above findings was disrupted in men, but preserved in women. When levels of activation to emotion faces was considerably lower than that to neutral faces, the pattern was generally preserved for men, but not for women. Preliminary tests were also conducted in an attempt to replicate previous reports that document a positive correlation between the risk allele of the serotonin transporter gene and amygdalae activation. The present study failed to replicate this pattern, perhaps on account of the relatively small sample size available when non-Caucasian participants were excluded from the analysis.

Major depressive disorder (MDD) and bipolar disorder (BD) are psychiatric diseases that affect behavior and impair cognition. A gene important to these disorders is the brain derived neurotrophic factor (BDNF) which is involved in processes controlling neuroplasticity. Previous studies have suggested that BDNF expression levels have to be finely regulated for normal mental health and cognition. This study therefore aimed to identify cis-regulatory elements that regulate BDNF promoter IV (BP4), which plays a role in mood and cognition, and investigated how polymorphisms in these cis-regulatory elements might alter BP4 activity contributing to MDD and BD. BP4-LacZ transgenic mice and primary neuron cultures were used to show that BP4 was active in the hippocampus, cortex and amygdala and responded to PKC, KCl and Wnt signaling activation. Using comparative genomics, two highly conserved regions were identified, BE5.1 and BE5.2, which contain the rs10767664 and rs12273363 polymorphisms respectively. Reporter gene assays in primary cultures derived from these brain structures showed that BE5.1 and BE5.2 were responsible for “filtering” or “gating” the effects of different combination of activated signal transduction pathways on BP4. Thus, BE5.1 increased BP4 response to forskolin in cortical cultures while abolishing BP4 response to PMA in hippocampal cultures. Similarly, BE5.2 permitted BP4 response to KCl and combined forskolin and PMA treatment, but not individual forskolin and PMA treatment nor LiCl in cortical cultures. Significantly, the minor allele of rs12273363, which has been associated with MDD and BD susceptibility, acted as a more potent repressor of BP4 response to neuron depolarization by KCl and PKA/PKC activation in different primary cultures. The possible relevance of these findings to the role of altered BDNF expression in MDD and BD are discussed.

Despite the success of available medical and psychosocial treatments, a sizable subgroup of individuals with commonly co-occurring disorders, generalized anxiety disorder (GAD) and major depressive disorder (MDD), fail to make sufficient treatment gains thereby prolonging their deficits in life functioning and satisfaction. Clinically, these patients often display temperamental features reflecting heightened sensitivity to underlying motivational systems related to threat/safety and reward/loss (e.g., somatic anxiety) as well as inordinate negative self-referential processing (e.g., worry, rumination). This profile may reflect disruption in two important neural networks associated with emotional/motivational salience (e.g., salience network) and self-referentiality (e.g., default network, DN). Emotion Regulation Therapy (ERT) was developed to target this hypothesized profile and its neurobehavioral markers. In the present study, 22 GAD patients (with and without MDD) completed resting state MRI scans before receiving 16 sessions of ERT. To test study these hypotheses, we examined the associations between baseline patterns of intrinsic functional connectivity (iFC) of the insula and of hubs within the DN (anterior and dorsal medial prefrontal cortex [MPFC] and posterior cingulate cortex [PCC]) and treatment-related changes in worry, somatic anxiety symptoms and decentering. Results suggest that greater treatment linked reductions in worry were associated with iFC clusters in both the insular and parietal cortices. Greater treatment linked gains in decentering, a metacognitive process that involves the capacity to observe items that arise in the mind with healthy psychological distance that is targeted by ERT, was associated with iFC clusters in the anterior and posterior DN. The current study adds to the growing body of research implicating disruptions in the default and salience networks as promising targets of treatment for GAD with and without co-occurring MDD.

O transtorno depressivo maior (TDM) é uma condição de saúde muito prevalente na população geral e de trabalhadores e está associado a grande impacto socioeconômico, principalmente às custas da incapacidades funcionais e queda da p rodutividade. Dados da OMS apontam a depressão como a principal causa de YLD no mundo. No Brasil, é a terceira causa de concessão dos benefícios do INSS, sendo que ambas têm estimativas crescentes para a próxima década. As mudanças que vêm ocorrendo no uni verso do trabalho, desde metade do século XX, podem estar relacionadas o aumento da prevalência de absenteísmo doença por depressão, principalmente às custas de exposição dos trabalhadores a fatores psicossociais mais adversos e, também, pela maior exigênc ia de habilidades e recursos mentais pelo mercado de trabalho. Assim, pensar estratégias de ação em saúde do trabalhador que modifiquem os elevados índices de adoecimento e afastamento do trabalho passa, necessariamente, por conhecer os fatores associados a estes desfechos. A literatura disponibiliza dados sobre estes determinantes, mas não há registros realizados em território nacional. E este estudo pretende contribuir com esta lacuna ao estudar os fatores associados ao absenteísmo doença em amostra de tr abalhadores formais com TDM de uma universidade pública do Estado de São Paulo. Para esta finalidade, primeiramente foi feita validação de uma escala para caracterização objetiva da funcionalidade em sujeitos com TDM (N=44 casos e 44 não casos), a escala F AST. Em seguida, uma amostra de 172 trabalhadores, recrutados em serviços de saúde do trabalhador e assistencial especializado e que tiveram diagnóstico de TDM a partir da M.I.N.I., foi dividida em dois grupos: ativos no trabalho (N=76) e em absenteísmo do ença (N=96). A coleta dos dados foi feita por meio de entrevista face a face para aplicação do questionário elaborado para este estudo. A amostra foi caraterizada a partir dos dados socioeconômicos, hábitos e estilo de vida, funcionalidade a partir da esca la FAST, condições e fatores psicossociais no trabalho, características clínicas e de personalidade. A comparação entre os grupos foi realizada por meio de análises bivariadas pelo teste de Fisher e o estudo dos fatores associados ao absenteísmo doença foi feita por meio da regressão logística multivariada, no modelo hierarquizado, no programa STATA 13. Para todas as análises, foram consideradas significativas aquelas com p value menor que 5% com IC 95% e a importância relativa dos fatores sobre o desfecho foi avaliada pelo Odds Ratio . A taxa de resposta foi de 89,2 %. Houve predomínio de mulheres (72,1%), da faixa etária de 50 a 54 anos (29,6%), casados (72,6%) e com escolaridade nível fundamental ou médio (80,2%). O grupo de ativos foi composto por 76 sujei tos (44,18%) e o de inativos por 96 (55,81%). Os resultados encontrados apontaram que a funcionalidade aferida a partir da escala FAST é bastante impactada pelo episódio depressivo e está diretamente relacionada à severidade dos sintomas. Sobre o absenteís mo doença, os resultados apontaram que o determinante mais incisivo foi a severidade da depressão (OR 86,3 [IC 95%: 7,57 984,4]), seguida, de maneira menos impactante, pelos determinantes ocupacionais como autonomia e trabalho estressante como fatores de risco e trabalho interessante como fator de proteção. Em relação às características pessoais, ter boa habilidade para lidar com adversidades se mostrou fator de proteção para o desfecho. Observa com adversidades se mostrou fator de proteção para o desfecho. Observa--se a se a complexidade das relações entre os determinantes e o decomplexidade das relações entre os determinantes e o desfecho apontando que as sfecho apontando que as estratégias de intervenção devem ser multidisciplinares e intersetoriais. estratégias de intervenção devem ser multidisciplinares e intersetoriais. / Major Depressive Disorder (MDD) is a health condition very prevalent in the general population and of workers and is associated with great socioeconomic impact, mainly at the expense of functional disability and falling productivity. WHO data indicate depression as the main cause of YLD in the world. In Brazil, is the third cause of granting the benefits of INSS, both of which have increased estimates for the next decade. The changes that have been taking place in the world of work, since the mid twentieth centur y, can be linked the increased prevalence of absenteeism for depression, mainly at the expense of workers exposure to psychosocial factors more in adverse and greater demand for skills and mental resources by the labour market. So, think action strategies on occupational health that modify the high rates of illness and departure from work passes, necessarily, to meet the factors associated with these outcomes. The literature provides data on the determinants, but there are no records held in the national te rritory. The aim of this study was to observe the factors that associate with the absenteeism in subjects with MDD in sample of formal workers of a public university in São Paulo, Brazil. It is a cross sectional study in convenience sample of selected work ers in specialized social assistance and occupational health of the university. Totaled if 172 workers diagnosed with MDD from M.I.N.I. that were divided into two groups: active at work ( and in absenteeism (N= The data collection was made by using face to face interview for application of the questionnaire developed for this study. The sample was characterized from the socioeconomic data, habits and lifestyle, functionality from FAST scale, conditions and psychosocial factors at work, clinical char acteristics and personality. The comparison between the groups was performed by means of bivariate analyses by Fisher´s test and the study of factor associated with absenteeism was made by means of multivariate logistic regression, hierarchical model in ST ATA program 13. For all analysis, were considered significant with p value < and the importance on the factors about the outcome was assessed by the Odds Ratio. The response rate was 82,2 There was a predominance of women ( age 50 to 54 years (2 9,6%), married ( and with fundamental level or medium education ( The active group was composed of 76 subjects ( and the absenteeism group for 96 ( The results showed that the measured feature from the FAST scale is very impacte d by the MMD and is directly related to the severity of symptoms. About the absenteeism, the results showed that the most incisive determinant was the severity of depression [OR 86,3 ( 7,57 984,4)], then in a manner less impact by occupational determi nants such as autonomy and stressful job as risk factors and interesting work as protection factor. In relation to personal characteristics, have good ability to handle adversity proved to factor the outcome. Noted the complexity of the relationship betwee n the determinants and the closure pointing out that the intervention strategies must be multidisciplinary and intersectoral.

Major depressive disorder (MDD) is rapidly growing among the population. A widely believed neurobiological explanation is that the symptoms arise due to an imbalance of the neurotransmitter serotonin. Therefore, the most provided antidepressant is currently selective serotonin reuptake inhibitors (SSRI), which increase the serotonin in the synaptic cleft by inhibit the reuptake of serotonin. There are medications which challenge the serotonin hypothesis such as tianeptine. Tianeptine increases the reuptake of serotonin in the synaptic cleft and thus decreasing the serotonin levels. The thesis has three aims: First, to investigate what mechanisms tianeptine and SSRI work upon. Second, compare the efficiency of SSRI and tianeptine. Third, if the two agents display any differences in adverse side effects. A systematic review and search through relevant databases were made to obtain results. The main findings of this thesis were the two agents act differently of many aspects of the brain mechanisms and neurochemistry such as the cannabinoid system, expression of different cell types and their dependence of protein kinase. Even so, the results show that both agents are equally efficient in treating the depressive symptoms in the larger context, although some interesting findings are seen when zooming in. Anxiety is often comorbid with depression and even though both tianeptine and SSRI are shown to reduce these symptoms during chronic administration, SSRI can produce an anxiogenic effect in the beginning. Another noteworthy finding was that tianeptine showed to be clinically significant, but so did placebo. The third aim investigated the differences in side-effects between these two agents, and both agents were equally safe in number of adverse side-effects. Though tianeptine showed to have some slight advantages in manners of sexual dysfunction and the item 3 on the CGI scale.

A presença de tentativas de suicídio vem sendo associada à comorbidade com transtornos de ansiedade, tanto em estudos retrospectivos como nos prospectivos em pacientes com transtorno depressivo maior e naqueles com transtorno bipolar, embora os estudos apresentem resultados conflitantes. O objetivo deste estudo foi avaliar, prospectivamente, o impacto da presença da comorbidade com os transtornos ansiosos na presença de tentativas de suicídio em pacientes com transtornos do humor, durante o seguimento de 2 anos. Foram avaliados 667 pacientes, divididos em dois grupos: um grupo com comorbidade com transtorno ansioso (N+229, 34,3% e outro sem a comorbidade (N=438, 65,7%) em um estudo prospectivo com duração de 2 anos. As avaliações foram realizadas à entrada do estudo, após 3 meses, 12 meses e 24 meses. As escalas utilizadas nas avaliações foram: Escala de Depressão de Hamilton-24 itens, Escala de Desesperança de Beck, Escala de Ideação Suicida de Beck, Escala de Impulsividade de Barrat, BrownGoodwin Aggression Inventory, Buss-Durkeee Hostility Inventory e a Columbia Suicide History Form para avaliação da presença de tentativas de suicídio. Sintomas ansiosos foram avaliados por meio dos subitens: agitação, ansiedade psíquica, ansiedade somática e hipocondria presentes na Escala de Depressão de Hamilton. A medida de desfecho foi a presença de tentativa de suicídio durante o seguimento. Curvas de sobrevivência de Kaplan-Meier foram utilizadas para avaliar a relação entre a presença de tentativas de suicídio no seguimento e a presença de comorbidade com transtorno ansioso à entrada do estudo. A regressão de Cox foi empregada para avaliar quais outros fatores de risco incluindo os sintomas ansiosos estariam associados à presença de tentativas de suicídio no seguimento. Os resultados mostraram que 63 pacientes (13,1%) tiveram tentativa durante o seguimento. Não houve diferença entre os pacientes com e sem comorbidade com transtorno ansioso (log-rank 0,269 p=0.604. Na regressão de Cox, sexo feminino (HR 4.088 p <= 0.001), tentativas de suicídio prévias (HR 3,17, p=0,002), e escores de hostilidade (HR 1,06 p <= 0,001) foram preditores de tentativas de suicídio durante o seguimento. A presença de sintomas hipocondríacos foi um fator protetor para tentativas durante o seguimento (HR 0,60, p=0,011). Contrariamente a alguns estudos retrospectivos, neste estudo a comorbidade com transtornos ansiosos não foi um fator de risco para tentativas de suicídio no seguimento em pacientes com transtornos de humor / Suicide attempts have been associated with comorbidity with anxiety disorders in cross-sectional studies in both major depression and bipolar disorder, although not all studies agree. Our aim was to prospectively test the impact of comorbid anxiety disorders on future suicide attempts in a sample of mood disordered patients. A two-year prospective study evaluated 667 patients divided in two groups: patients with comorbid anxiety disorders (N=229, 34.3%) and patients without the comorbidity (N=438, 65.7%) Assessments were performed at baseline and after 3, 12 and 24 months. The main outcome was the occurrence of suicide attempts during follow-up. The scales used in the patient\'s evaluation were: Hamilton Depression Rating Scale-24 items, Beck Hopelessness Scale, Scale for Suicide Ideation, Barrat Impulsiveness Scale, Brown-Goodwin Aggression Inventory, Buss-Durkeee Hostility Inventory and Columbia Suicide History Form To evaluate the presence of attempts. Anxiety symptoms were evaluated using the sub-items agitation, psychic anxiety, somatic anxiety and hypochondria. Kaplan-Meier survival curves were used to elucidate the relationship between presence of lifetime anxiety disorders and subsequent suicide attempts. Cox proportional Hazard regression was performed to investigate other risk factors associated with suicide attempts during follow-up, including anxiety symptoms at baseline (somatic anxiety, psychic anxiety, agitation and hypochondriasis). There were 63 patients (13.1%) with suicide attempts during follow-up. There were no differences in survival curves for presence of comorbid anxiety disorders ( log-rank test 0.269 p= 0.604). In the Cox proportional hazard regression female sex (HR 4.088 p <= 0.001), past suicide attempts (HR 3.17, p=0.002), and hostility scores (HR 1.06 p <= 0.001) were the strongest predictors for suicide attempts. Hypochondriac symptoms were a protective factor for future suicide attempts (HR 0.60, p=0.011). Contrary to some cross-sectional studies, our results suggest that comorbidity with anxiety disorders is not a risk factor for future suicide attempts in patients with MDD or BD