Major depression disorder is increasing globally, causing great personal suffering and economic burdens to society. Current antidepressant medications are not sufficiently able to treat all cases of depression and are often associated with troubling side effects. There is a great need for the development of novel treatments, and classic psychedelic drugs are currently being investigated with new interest. The legal status has hindered research, but promising results from pioneering studies on the antidepressant effect of psilocybin have recently given psilocybin breakthrough therapy status, allowing further research to occur more freely. This systematic review aims to investigate the literature available on psilocybin’s effect on major depressive disorder. Five studies were selected according to set inclusion and exclusion criteria. Results are suggesting that psilocybin combined with psychological support is a fast-acting antidepressant agent, able to produce a sustained decrease in symptoms of depression with minimal side effects. However, current studies come with several limitations and further research is needed before the antidepressant effect of psilocybin can be stated as a fact.

<p> Major Depressive Disorder (MDD) is a common affective disorder associated with persistent states of negative mood and selective cognitive impairments. Fronto-temporal dysregulation in MDD patients is thought to contribute to the symptoms seen in these patients.</p> <p> Based on prior evidence of structural and functional alterations in the hippocampus (Hc) and prefrontal cortex (PFC) in MDD patients, we were interested in examining the changes in cerebral function that underlie the cognitive dysfunction seen in two different MDD populations. We studied psychotropically naïve depressed patients experiencing their first treated episode (FTE) of depression, MDD patients who had experienced multiple past treated episodes (MTE) of MDD and healthy controls.</p> <p> Two functional magnetic resonance imaging studies (fMRI) were conducted. The first study used an Hc dependent process dissociation task to examine Hc activation during recollection memory. The second fMRI study examined the activation in the PFC during reward and punishment conditions of a reversal-learning paradigm. Finally, we conducted magnetic resonance spectroscopy scans to measure levels of metabolites indicative of neuronal and glial cell integrity in the Hc of depressed patients and controls. </p> <p> We observed differing results across all three studies in our FTE and MTE depression groups. Our studies examining the Hc suggest that MTE patients have decreased activation in this region as well as corresponding memory errors during recollection memory. Additionally, these patients have smaller Hc volume and signs of increased neuronal membrane turnover. Conversely, our FTE patients displayed heightened Hc activation without memory deficits. Moreover, FTE patients had signs of increased glial cell density in the Hc without volumetric differences in this region. Our examination of reward processing revealed several health-to-illness gradients of activation in areas as the nucleus accumbens, anterior cingulate and ventral prefrontal cortices during the processing of rewards and punishers. </p> <p> These findings suggest that several regions in the brain may be sensitive to the impact of disease burden and repeated episodes of MDD. In the Hc, first treatment patients may engage in compensatory processes during the early stages of illness that are attenuated with repeated episodes of illness. Moreover, reward processing may be affected in the early course of the disorder, however with a protracted course of illness these regional alterations in activation become more pronounced.</p> / Thesis / Doctor of Philosophy (PhD)

Major Depressive Disorder (MDD) is one of the most common psychiatric conditions affecting adults and afflicts approximately 5% of the world's population. MDD is highly co-morbid with cardiovascular disease, a major source of morbidity and mortality. Although a number of pathological changes observed in MDD may impact cardiovascular health, no single mechanism has been identified that can explain this association. Both MDD and CVD are more common in women, and pregnancy may represent a period of elevated risk for both depression and changes in cardiovascular health that may never fully resolve in the years following pregnancy. This study of 61 pregnant women during their third trimester of pregnancy investigated whether depressive symptoms (as measured by the Edinburgh Postnatal Depression Scale, or EPDS) are associated with decreased heart rate variability, a well-known marker of cardiovascular risk. Additionally, this study will investigate whether Plasminogen Activator Inhibitor-1 and 2 (PAI-1 and PAI-2) mediate this association. These pro-thrombotic proteins have long been linked to the presence and severity of cardiovascular disease, and an emerging body of evidence suggests that plasma concentrations of these proteins may also be elevated in Major Depressive Disorder. Heart rate variability was significantly reduced among participants who had clinically significant depressive symptoms during the third trimester (EPDS >14), although adjustment for age, body mass index, smoking, education level and use of psychiatric medication fully attenuated this relationship. PAI-1 and PAI-2 measured via ELISA assay in a subset of the study population (n=23) was found to not mediate this association. This study is the first of its kind to evaluate the role of PAI-1 in psychiatric illness during pregnancy, and may serve as the impetus for further research aimed at elucidating the relationship between mental health and cardiovascular risk during gestation. / Thesis / Master of Science (MSc)

Major Depressive Disorder (MDD) is a severe psychiatric disorder affecting approximately 12% of men and 25% of women nationally in the nonclinical population. The aim of this research was to determine if lay individuals could differentiate between MDD and normal sadness. To evaluate the lay understanding of MDD and normal sadness, students at a large Southeastern university read four vignettes describing varying severity levels of MDD and normal sadness and then answered a variety of questions relating to the vignettes. Additionally, the lay conceptualizations of MDD were compared and contrasted to the professional conceptualizations of MDD. The principal hypothesis was that lay individuals could not differentiate between clinical depression and normal sadness because the two concepts have become synonymous in today’s society. In fact, results showed that lay individuals could not differentiate between threshold MDD and subthreshold MDD.

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.

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.

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