O Transtorno Depressivo Maior (TDM) é uma condição psiquiátrica que afeta 4,4% da população mundial, exibindo um substancial sofrimento pessoal, incapacidade e custos sociais, e estima-se que ele será a principal causa de incapacidade no mundo em 2030. O surgimento de novas ferramentas e modelos de pesquisa envolvendo o TDM irá auxiliar no entendimento desta doença. Deste modo, o objetivo deste trabalho foi gerar uma coleção de células-tronco pluripotentes induzidas humanas (hiPSCs) de um grupo de indivíduos com TDM. Foram coletadas amostras de células mononucleares (MNCs) de 66 indivíduos afetados, e geradas 6 linhagens de hiPSCs. Através de diversos testes de caracterização, a pluripotência destas células foi confirmada. Além disto, também foi padronizada a diferenciação destas hiPSCs em neurônios serotonérgicos. Neurônios derivados dessas hiPSCs poderão constituir material de estudo para outros grupos de pesquisa interessados no estudo da TDM, e ser utilizados em testes futuros para prever resposta a medicamentos. / Major Depressive Disorder (MDD) is a psychiatric condition that affects 4.4% of the world\'s population, exhibiting substantial personal suffering, disability and social costs, and is estimated to be the leading cause of disability in the world by 2030. Emergence of new tools and research models involving TDM will aid in the understanding of this disease. Thus, the objective of this work was to generate a collection of human induced pluripotent stem cells (hiPSCs) from a group of individuals with MDD. Samples of mononuclear cells (MNCs) of 66 affected individuals were collected, and 6 lines of hiPSCs were generated. Through several characterization tests, the pluripotency of these cells was confirmed. In addition, the differentiation of these hiPSCs into serotonergic neurons was also standardized. Neurons derived from these hiPSCs could constitute study material for other research groups interested in the study of MDD, and be used in future tests to predict drug response.

This thesis aimed to extend the existing psychological and neural basis of social processing in Major Depressive Disorder. This investigation was an attempt to resolve current conflicts and gaps in the social affective neuroscience literature regarding social functioning in depression. Chapter 1 consisted of a general introduction to the current evidence-base and theoretical frameworks surrounding social processing more generally, and in depression more specifically. ‎Chapter 2 provided an exploration of the systemic behavioural biases in in those with depression compared to mentally healthy individuals using a range of social, affective and process measures implemented across the remaining chapters. Then followed a behavioural and neural investigation into self-relevant social processing in depression. Chapter 3 described the process of memory generation implemented across ‎ Chapter 4-6 using a script-driven paradigm. It further discussed the ecological validity of this paradigm using social autobiographical memories. Chapter 4 investigated the neural and behavioural responses to self-relevant autobiographical memories of social rejection and social inclusion in individuals with depression and in healthy controls. The next two chapters discussed the behavioural and neural basis of social processing in depression in response to others’ memories of social rejection and inclusion, using traditional and novel fMRI analysis methodologies in ‎Chapter 5 and ‎‎Chapter 6, respectively. The latter applied a novel intersubject correlation analysis to the same population of depressed and healthy controls as in Chapter 5. Then, Chapter 7 presented a future application of the script-driven imagery paradigm by investigating the effectiveness of different emotion regulation strategies in response to socially salient autobiographical memories in a population of healthy controls. Finally, Chapter 8 provided a general discussion bringing together behavioural and neural findings to provide a clearer understanding of social processing in Major Depressive Disorder. Current theoretical frameworks were used to guide the interpretation of these findings.

Os Transtornos psiquiátricos acompanham a história da humanidade. Classificados em categorias distintas podemos observar que dentre todas as patologias que constituem os transtornos mentais e de comportamento, as doenças mais prevalentes são as doenças de Ansiedade e de Transtorno Depressivo Maior (TDM). Mesmo com muitos avanços nas neurociências, assim como na terapêutica (psicofarmacologia), ainda hoje a fisiopatologia e o desenvolvimento farmacológico são áreas que necessitam intenso estudo. Avanços recentes tem sugerido que drogas capazes de modular os sistemas glutamatérgico e purinérgico possuem potencial efeito neuromodulador, sendo promissores candidatos para o desenvolvimento de novas drogas com ação ansiolítica e/ou antidepressiva. Dessa maneira, o objetivo desta tese foi investigar o potencial efeito ansiolítico da guanosina (GUO) em modelos animais preditivos para o estudo da potencial atividade ansiolítica de novos compostos, assim como seu potencial efeito antidepressivo no modelo animal de depressão da Bulbectomia Olfatória Bilateral (OBX). Inicialmente, nossos resultados demonstram que a administração de GUO foi capaz de produzir um consistente efeito ansiolítico modulando os níveis de adenosina (ADO) e glutamato cerebral. Ainda, pela primeira vez, foi observado que a GUO per se promoveu uma diminuição da liberação de glutamato em preparações de sinaptosomas de hipocampo, um efeito dependente da ativação dos receptores A1 de ADO. Após a caracterização do potencial efeito ansiolítico da GUO, nosso objetivo foi avaliar o potencial efeito antidepressivo da GUO em um modelo animal com validade de face e de constructo, como o modelo da OBX. Contudo, após revisão da literatura em estudos que utilizaram o modelo da OBX, observou-se a necessidade de uma investigação a longo prazo, das principais alterações comportamentais e neuroquímicas induzidas pela OBX. Nossos resultados, mostram pela primeira vez, que camundongos submetidos a OBX apresentaram simultaneamente alterações comportamentais e neuroquímicas transitórias e de longa duração. Ademais, as evidências indicam que o hipocampo possui alta susceptibilidade aos danos induzidos pela OBX, visto que uma sinaptotoxicidade transitória, acompanhada de um duradouro desequilíbrio redox e aumento da resposta inflamatória foram observados. Por fim, o tratamento crônico com GUO foi capaz de reverter a maioria das alterações identificadas previamente como duradouras nos parâmetros comportamentais e neuroquímicos no modelo da OBX. Considerando os resultados neuroquímicos obtidos pelos diferentes protocolos de tratamento realizados neste estudo, novas hipóteses de mecanismos de ação exercidos pela GUO foram apresentadas, e mecanismos já estabelecidos foram reproduzidos. Por fim, de uma maneira geral os dados apresentados nesta tese reforçam a hipótese do envolvimento do sistema purinérgico nos transtornos psiquiátricos, e sugerem que a GUO apresenta uma potencial ação terapêutica para o tratamento destas doenças, abrindo assim novas perspectivas para elucidação dos mecanismos envolvidos na fisiopatologia da ansiedade e TDM. / Psychiatric disorder had accompanied the course of human history. Mental and behavioral disorders are classified in different categories and among all different psychiatric disorders; anxiety and major depressive disorder (MDD) are the most prevalents. Despite the substantial advances in our knowledge on the neurobiological bases of both anxiety and MDD, as well as in the therapeutic area (psychopharmacology), even today, the pathophysiology of these disorders as well as pharmacological development are still under investigation. Recent advances have suggested that drugs able to modulate glutamatergic and purinergic systems present a potential neuromodulatory effect, and are promising candidates for the development of new drugs with both anxiolytic and antidepressant effects. Thus, the aim of this work was to investigate the potential guanosine (GUO) anxiolytic-like effects in predictive animal models largely used to elucidate anxiolytic properties of new compounds, as well as investigate the potential GUO antidepressant effect in Olfactory Bulbectomy (OBX) model of depression. Initially, our results demonstrate that acute GUO administration was able to induce a consistent anxiolytic-like effect, by modulating the adenosine and glutamate cerebrospinal levels. Here, for the first time, it was observed that GUO per se was able to decrease the glutamate release in hippocampal synaptosome. After characterizing the potential anxiolytic-like effect promoted by GUO, our second goal was to evaluate the potential GUO antidepressant-like effect in an animal model with recognized face and construct validity as the OBX model of depression. However, given the lack of studies in the literature considering the time course of the behavioral and neurochemical changes after the depressive-like behavior onset induced by OBX we firstly characterize some important features regarding the OBX model. Collectively, mice submitted to the OBX model of depression and followed up to 8 weeks simultaneously presented transient and long-lasting deleterious effects in behavioral and neurochemical parameters. The evidences pointed that hippocampus was the most affected brain structure, since a transient hippocampal-related synaptotoxicity, accompanied by a long-lasting hippocampal imbalance in redox and inflammatory homeostasis were observed. Additionally, the neurochemical effects seem to strengthen our behavioral findings. Finally, chronic GUO treatment, similarly to the classical tricyclic antidepressant imipramine, was able to improve the long-term behavioral phenotype impairment induced by OBX, specifically improving behavioral performances that require cognitive functions, accompanied by reversion of hippocampal redox imbalance parameters, as well as in peripheral and central anti-inflammatory IL-10 release. Thus, in present study, the pre-clinical evaluation of GUO as a potential drug for treatment of the most prevalent psychiatric disorders (anxiety and MDD) presented promising results. Furthermore, additional GUO mechanisms of action were evidenced and new perspectives were established. Thus, the data presented in this thesis support the hypothesis of the involvement of the purinergic system in mood disorders, and suggest that GUO has a potential therapeutic activity for the treatment of psychiatric disorders.

O objetivo do presente estudo foi avaliar preliminarmente a eficácia do grupo terapêutico de abordagem gestáltica no tratamento do Transtorno Depressivo Recorrente através da avaliação quantitativa dos sintomas depressivos, avaliação da qualidade de vida e adequação social. Foi um estudo aberto, exploratório, prospectivo, em pacientes que se encontravam em tratamento farmacológico para Transtorno Depressivo Recorrente, submetidos a dezesseis sessões de grupo terapêutico. Aplicou--se no início e no fim do tratamento: Entrevista Clínica Estruturada para o DSM-IV: Transtorno do Eixo I, 17-item Hamilton Depression Rating Scale, Medical Outcomes Study 36-item Short-Form Health Survey e Escala de Auto-Avaliação de Adequação Social. Sete pacientes terminaram as dezesseis semanas de tratamento. Observou-se melhora clínica em relação aos sintomas depressivos. Em relação à qualidade de vida, apresentaram melhora nos domínios da capacidade funcional; estado geral da saúde; saúde mental e dor. Perceberam-se inadequados em relação à adequação social, porém apresentaram indicadores clínicos de melhora após grupo terapêutico. Resultados sugerem que a participação no grupo terapêutico de abordagem gestáltica pode auxiliar na redução da sintomatologia depressiva, em certos domínios da qualidade de vida e em ganhos clínicos. Estudos com amostras maiores, com grupo controle e com melhor avaliação da adequação social e funcionalidade dos pacientes são necessários / The intention of this study was to make a preliminarily evaluation of the effectiveness of gestalt group therapy in the treatment of major depression through the quantitative assessment of the symptoms of depression and an assessment of quality of life and social functioning. The open study was of an exploratory nature and involved patients who were undergoing pharmacological treatment for major depression and who participated in sixteen gestalt group therapy sessions. The effectiveness of the therapeutic process was assessed by Structured Clinical Interviews at the beginning and at the end of treatment at which were applied the DSM-IV: Disorder Axis I, 17-item Hamilton Depression Rating Scale, Medical Outcomes Study 36-item Short-Form Health Survey Scale and Self-Assessment of Social Adequacy. Seven patients completed the sixteen weeks of treatment. A clinical improvement in the depressive symptoms was observed. With regard to quality of life, the patients showed improvement in their physical functioning, general health, mental health and bodily pain. They considered themselves poorly adjusted to society and presented improved clinical indicators after group therapy. The results suggest that participation in gestalt group therapy can help reduce the symptoms of depression, improve some areas of quality of life and demonstrate clinical gains. Further studies with a larger sample, the use of a control group and improved assessment methods of social adequacy and functionality are needed

It is estimated that approximately 30% of individuals worldwide are affected by mental health problems during their lifetime. Currently, Major Depressive Disorder (MDD) is one of the most prevalent psychiatric disorders and a leading cause of non-lethal disability worldwide. However, despite exposure to known risk factors for MDD, human responses to it vary widely. Whilst some individuals develop MDD, others develop only mild and transient symptoms or no depressive symptomology at all. This ability to 'bounce back' from or 'escape' the development of psychiatric illness is referred to as psychological resilience (Chapter 1). Scientific and clinical interest in resilience has grown exponentially over recent decades, but wide discrepancies are still found in both its definition and measurement. As such, resilience is rarely measured directly, but inferred from the measurement of two specific points of convergence; adversity (its antecedents) and positive adaptation (its consequences). Whilst the study of adversity and positive adaptation has informed our knowledge of resilience it often fails to consider other putative risk factors for MDD (such as genetics), or potential protective factors that may foster resilience despite risk. More recently, examining protective factors have become a focus of research in relation to resilience. This research suggests that numerous protective factors coalesce to contribute to resilient outcomes which give rise to a dynamic resilience process that varies contextually and temporally. Although investigating resilience may be expected to reveal similar findings to studying MDD itself, it does represent a new facet to scientific and clinical research. Specifically, resilience focuses on intervention long before the development of MDD when effects on subsequent suffering may be ameliorated. For this reason, it is imperative to address the concept of resilience, concentrating on the core components of adversity, positive adaptation and protective factors, to move beyond description towards an understanding of individual differences in resilience (Chapter 2). In this thesis, three studies will be presented which aim to examine psychological resilience from multiple perspectives to further delineate the concept. In Chapter 3, the associations and interactions between neuroticism and general intelligence (g) on MDD, and psychological distress were examined in GS:SFHS (Generation Scotland: Scottish Family Health Study) to investigate whether g mitigates the detrimental effects of neuroticism on mental health, as such an association has previously been identified for physical health and mortality. A larger replication was also performed in UK Biobank using a self-reported measure of depression. Across two large samples it was found that intelligence provides protection against psychological distress and self-reported depression in individuals high in neuroticism, but intelligence confers no such protection against clinical MDD in those high in neuroticism. In Chapter 4, a new dataset is presented which was designed to investigate psychological resilience and mental health. Specifically, the STRADL (Stratifying Resilience and Depression Longitudinally) dataset aimed to re-contact existing GS:SFHS participants to obtain repeat measures of MDD and psychological distress in addition to obtaining data on resilience, coping style and adverse life experiences. This dataset has the potential to identify mechanisms and pathways to resilience but also elucidate causal mechanisms and pathways of depression sub-types. Chapter 5 investigated whether neuroticism and resilience are downstream mediators of genetic risk for depression, and whether they contribute independently to such risk. Specifically, the moderating and mediating relationships between polygenic risk scores (PRS) for depression, neuroticism, resilience, and both clinical and self-reported MDD were examined in STRADL. Regression analyses indicated that neuroticism and PRS for depression independently associated with increased risk for both clinical and self-reported MDD, whereas resilience associated with reduced risk. Structural equation modelling suggested that polygenic risk for depression associates with vulnerability for both clinical and self-reported MDD through two partially independent mediating mechanisms in which neuroticism increases vulnerability and resilience reduces it. In Chapter 6, the proportion of phenotypic variance that is attributable to genetic and shared-familial environment was estimated for resilience and three main coping styles; task-, emotion-, and avoidance-oriented coping. Bivariate analyses were conducted to estimate the genetic correlations between these traits and neuroticism. Our results indicate that common genetics affect both resilience and coping style. However, in addition, early shared-environmental effects from the nuclear family influence resilience whereas recent shared-environment effects from a spouse influence coping style. Furthermore, strong genetic overlap between resilience, emotion-oriented coping, and neuroticism suggests a relationship whereby genetic factors that increase negative emotionality lead to decreased resilience. These studies highlight the necessity for complementary multivariate techniques in resilience research to elucidate tractable methodologies to potentially identify mechanisms and modifiable risk factors to protect against psychiatric illness (Chapter 7).

A depressão é o mais comum dos distúrbios afetivos. Afeta ao menos 10% da população idosa do Brasil. Nos idosos, alguns fatores ligados ao metabolismo parecem estar bastante relacionados a esse transtorno, como uma menor concentração de noradrenalina e serotonina (5-HT) e uma maior atividade da monoaminooxidase em relação a adultos jovens. Os inibidores seletivos da recaptação da serotonina (ISRS), principalmente a sertralina, são a primeira opção no tratamento da fase aguda e manutenção dos episódios depressivos em idosos. As plaquetas vêm sendo amplamente utilizadas como modelo para estudar na periferia alterações que ocorrem no sistema nervoso central. A 5-HT apesar de ser primordialmente expressa no cérebro, também pode ser encontrada em plaquetas. Este neurotransmissor está envolvido em inúmeros aspectos do funcionamento normal do cérebro desde a regulação do humor até a regulação hormonal. A deficiência nos níveis de 5-HT pode estar intimamente ligada a alguma anormalidade na atividade da glicogênio sintase quinase 3B(GSK3B). Esta enzima exerce funções no metabolismo celular que vão desde sobrevivência celular, metabolismo e processamento de proteínas, até processos cognitivos. A atividade da GSK3B é estreitamente regulada pela fosforilação. Fosforilação no sítio ser9 inativa a enzima, enquanto que a desfosforilação neste mesmo sítio ativa a enzima. Diversos estudos têm mostrado que a forma inativa da enzima exerce um efeito neuroprotetor. O objetivo do presente estudo foi verificar a influência do tratamento com sertralina, em pacientes idosos com diagnóstico de depressão maior, sobre a 5- HT e GSK3B após 3 e 12 meses de tratamento. A quantificação da 5-HT foi realizada por HPLC e da GSK3B plaquetária, pelos métodos de ELISA e blotting, que se revelaram equivalentes. Após um ano de tratamento encontramos uma diminuição da 5-HT plaquetária nos pacientes com depressão maior com relação aos níveis basais, bem como um aumento da forma total da enzima GSK3B (GSKT), uma diminuição da forma fosforilada (pGSK) e da razão entre pGSK e GSKT (rGSK). Quando comparados os níveis de GSK3B de pacientes tratados por um ano e controles, observamos uma maior expressão de GSKT em pacientes; enquanto a pGSK e rGSK se mostraram equivalentes. Pudemos observar, portanto, uma modulação da 5-HT e da GSK3B pelo uso de sertralina. Essa modulação pode indicar que a ação antidepressiva deste fármaco pode estar associada a essas vias de sinalização / Depression is the most common affective disorders. It affects at least 10% of the elderly population of Brazil. In the elderly, some factors related to metabolism appear to be closely related to this disorder, such as lower concentration of noradrenaline and serotonin (5-HT) and increased monoamine oxidase activity in relation to young adults. The selective serotonin reuptake inhibitors (SSRI), especially sertraline are the first choice in treating acute and maintenance of depressive episodes in the elderly. Platelets have been widely used as a model to study in peripheral changes that occur in Central Nervous System. Although 5-HT is primarily expressed in the brain, it can also be found in platelets. This neurotransmitter is involved in numerous aspects of normal brain function since the regulation of mood to the hormonal regulation. A deficiency in 5-HT levels may be closely related to an abnormality in glycogen synthase kinase 3B (GSK3B) activity. This enzyme plays several functions in cell metabolism, ranging from cell survival, metabolism and protein processing, to cognitive processes. The GSK3B activity is tightly regulated by phosphorylation. Phosphorylation on Ser9 site inactives the enzyme, whereas dephosphorylation in the same site actives the enzyme. Several studies have shown that the inactive form of the enzyme plays a neuroprotective effect. The objective of this study was to investigate the influence of sertraline in elderly patients diagnosed with major depression, on platelet 5-HT and GSK3B after 3 and 12 months of treatment. Quantification of 5-HT was performed by HPLC and GSK3B by ELISA and western blotting. The methods for platelet GSK3B determination showed to be equivalent. After one year of treatment we found a decrease of platelet 5-HT in patients with major depression relative to their baseline levels, as well as an increase in the total form of GSK3B enzyme (GSKT), a decrease in phosphorylated form (pGSK) and the ratio between pGSK and GSKT (rGSK). Comparing the levels of GSK3B of patients with one year of treatment and controls, we found a higher GSKT expression in patients; while pGSK and rGSK showed to be equivalent. Therefore we observed a modulation of 5-HT and GSK3B by sertraline. This modulation may indicate that the antidepressant action of this drug may be associated with these signaling pathways

Cardiovascular disease (CVD) is the leading cause of death in the United States. Nearly half of the people diagnosed with heart failure (HF) die within 5 years of diagnosis. Brain abnormalities secondary to CVD have been observed in many discrete regions, including the hippocampus. Nearly 25% of patients with CVD also have major depressive disorder (MDD), and hippocampal dysfunction is a characteristic of both diseases. In this study, the hippocampus and an area of the hippocampal formation, the dentate gyrus (DG), were studied in a canine model of HF. Using this canine HF model previously, we have determined that myocardial infarction with mitral valve regurgitation (MI/MR) + spinal cord stimulation (SCS) can preserve cardiac function. The goal of this study was to determine if the SCS can also protect the brain in a similar fashion. Both the entire hippocampus and the DG tissues were dissected from canine brains and analyzed. These findings provide strong evidence that, in addition to the cardioprotective effects observed previously, SCS following MI/MR induces neuroprotective effects in the brain.

African Americans have a higher proclivity to depression than other ethnic groups in the United States and also have a greater propensity to avoid seeking professional mental health treatment. The available research has shown that racial and cultural barriers such as perceived discrimination and self-concealment are the primary factors that negatively affect African Americans' attitudes toward mental health itself and mental health treatment. Perceived discrimination and self-concealment may also negatively affect whether African Americans seek help for depression and from whom, but further investigation was needed. The quantitative survey study provided answers to which factors influence whether and where African Americans seek help for major depression. A total of 147 participants were recruited through word of mouth, local churches, community organizations, and virtual venues such as electronic mail and social media. Multivariate analysis of variance revealed the mean scores of African Americans' use of natural supports and their use of outpatient treatment (dependent variables) were not equal across all levels of their self-concealment, perceived discrimination, and depressive symptoms (independent variables). Multivariate analysis of covariance revealed that the mean scores remained the same when controlling for gender, income, education, and relationship status (covariates). The results suggest that the latter factors influence African Americans' decisions on where to seek help for depression regardless of their gender and socioeconomic status. Increasing the propensity of African Americans to seek professional help for depression should improve the mental health of the population as a whole and reduce the incidents of serious mental illness of those who are treated.

Major depressive disorder (MDD) is a debilitating disorder characterized by significant mood disturbance. In laboratory studies, MDD has been characterized by both blunted positive (PER) and negative emotional reactivity (NER). However, mood disordered persons' emotional reactivity has rarely been studied in naturalistic settings, and it is unknown how less severe forms of depression relate to emotional reactivity. To address these issues, the current study utilized two naturalistic sampling methods (the Day Reconstruction Method and the Experience Sampling Method) to examine PER and NER to daily life events in 35 individuals currently experiencing a major depressive episode (MDD), 26 individuals currently experiencing a minor depressive episode (mD), and 38 healthy controls. Both methods demonstrated that individuals with major and minor depression exhibited blunted PER relative to controls. In surprising contrast to previous laboratory findings, both individuals with MDD and mD showed increased NER relative to controls. Correlational analyses with severity measures indicated that depression and anxiety severity were positively related to NER and negatively related to PER. Findings suggest that NER in mood disorders may diverge as a function of assessment context and may be heightened in naturalistic environments. Despite the fact that mD is a milder mood disorder, findings suggest that mD results in similar emotional impairments as found in MDD.

Recent research in Australia has found that people with a mental illness experience higher mortality rates from preventable illnesses, such as cardiovascular disease, respiratory disease and diabetes compared to the general population. Lifestyle and other behavioural factors contribute significantly to these illnesses. Lifestyle behaviours that affect these illnesses include lack of physical activity, consumption of a poor diet and cigarette smoking. Research on the influence of these factors has been mainly directed towards the mainstream population in Australia. Consequently, there remains limited understanding of health behaviours among individuals with psychiatric disabilities, their health needs, or factors influencing their participation in protective health behaviours. This thesis presents findings from two studies. Study 1 evaluated the utility of the main components of Roger’s (1983) Protection Motivation Theory (PMT) to explain health behaviours among people with a mental illness. A clinical population of individuals with schizophrenia (N=83), Major Depressive Disorder (MDD) (N=70) and individuals without a mental illness (N=147) participated in the study. Respondents provided information on intentions and self-reported behaviour of engaging in physical activity, following a low-fat diet, and stopping smoking. Study 2 investigated the health care service needs of people with psychiatric disabilities (N=20). Results indicated that the prevalence of overweight, cigarette smoking and a sedentary lifestyle were significantly greater among people with a mental illness compared to that reported for individuals without a mental illness. Major predictors of the lack of intentions to adopt health behaviours among individuals with schizophrenia and MDD were high levels of fear of cardiovascular disease, lack of knowledge of correct dietary principles, lower self-efficacy, a limited social support network and a high level of psychiatric symptoms. In addition, findings demonstrated that psychiatric patients are disproportionately higher users of medical services, but they are under-users of preventive medical care services. These differences are primarily due to a lack of focus on preventive health, feelings of disempowerment and lower satisfaction of patient-doctor relationships. Implications of these results are discussed in terms of designing education and preventive programs for individuals with schizophrenia and MDD.