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 Ressonância Magnética e a Espectroscopia por Ressonância Magnética de Hidrogênio têm sido empregadas em estudos anatômicos e neuroquímicos do Transtorno Depressivo Maior (TDM). Dezenove crianças com TDM e 24 controles saudáveis foram avaliados em um magneto de 1,5 Tesla (Philips Intera 8.1.1.). Em comparação aos controles saudáveis, crianças com TDM apresentaram: menores volumes de hipocampo esquerdo; e no voxel único em CPFDL esquerdo: menores níveis dos compostos de colina, e maiores níveis de mio-inositol em CPFDL esquerdo. Menores níveis dos compostos de colina podem refletir uma diminuição da renovação de membranas. Maiores níveis de mio-inositol podem representar uma alteração no sistema de segundos mensageiros intracelulares / Magnetic resonance imaging and proton magnetic resonance spectroscopy have been applied to anatomical and neurochemical studies of Major Depressive Disorder (MDD). Nineteen children with MDD and 24 healthy controls were evaluated on a 1.5 Tesla (Philips Intera 8.1.1.) MRI. Compared to healthy controls, children with MDD presented: smaller left hippocampal volumes; and lower levels of choline-containing-compounds and higher myo-inositol levels in the left DLPFC. Lower levels of choline-containing-compounds in pediatric patients with MDD may reflect lower cell membrane turn-over. Higher myo-inositol levels in MDD may represent a disturbed secondary messengers system

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

A Ressonância Magnética e a Espectroscopia por Ressonância Magnética de Hidrogênio têm sido empregadas em estudos anatômicos e neuroquímicos do Transtorno Depressivo Maior (TDM). Dezenove crianças com TDM e 24 controles saudáveis foram avaliados em um magneto de 1,5 Tesla (Philips Intera 8.1.1.). Em comparação aos controles saudáveis, crianças com TDM apresentaram: menores volumes de hipocampo esquerdo; e no voxel único em CPFDL esquerdo: menores níveis dos compostos de colina, e maiores níveis de mio-inositol em CPFDL esquerdo. Menores níveis dos compostos de colina podem refletir uma diminuição da renovação de membranas. Maiores níveis de mio-inositol podem representar uma alteração no sistema de segundos mensageiros intracelulares / Magnetic resonance imaging and proton magnetic resonance spectroscopy have been applied to anatomical and neurochemical studies of Major Depressive Disorder (MDD). Nineteen children with MDD and 24 healthy controls were evaluated on a 1.5 Tesla (Philips Intera 8.1.1.) MRI. Compared to healthy controls, children with MDD presented: smaller left hippocampal volumes; and lower levels of choline-containing-compounds and higher myo-inositol levels in the left DLPFC. Lower levels of choline-containing-compounds in pediatric patients with MDD may reflect lower cell membrane turn-over. Higher myo-inositol levels in MDD may represent a disturbed secondary messengers system

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.

Psychosocial support from family is important in outpatient treatment programs for individuals with depressive disorder. The purpose of this phenomenological study was to explore the lived experiences and perceptions of parents of patients with depressive disorder regarding intensive outpatient treatment. The research question was what are the experiences and perceptions of parents of patients with depression regarding their role as caretakers in intensive outpatient treatment? The conceptual framework was a biopsychosocial framework and family systems theory. Content analysis was used to analyze data provided from interviews with parent participants (n = 8). Many participants reported high levels of involvement with various forms of support. They maintained positive relations with professionals, were involved in patient socialization, and facilitated adherence to patients' treatment plans. The results of this study indicated that family caregivers experienced ambivalent emotions toward their roles and patients. Findings also indicated experiences of exhaustion, strong emotions about the burden of having to support the patient, and concern for their own and the rest of the family's well-being. Future researchers should study these aspects further. Researchers, clinical practitioners, and policy makers must increase efforts to support those who help family members suffering from depression to intensify the search for effective ways to reduce the toll on those caregivers. Because of these findings, researchers could expand literature to illuminate the decisions and practices of psychotherapists, leading to improvements in intensive treatment programs for both patients and their caretakers. This study impacts social change by providing insights to aid policy makers in ensuring that outpatients receive the best treatment program available and that their primary caretakers are psychologically prepared and healthy.

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.

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.

<p>Individuals afflicted with childhood and adolescent mental disorders have an increased risk for poor outcome in adulthood. The progression of psychopathology from childhood to adult life may be influenced by a multitude of interacting variables, both biological and psychosocial. There is limited information on the relationships between child psychopathology and adult personality and personality disorders. The main aim of this thesis was therefore to gain better knowledge concerning adult personality outcome in patients with early onset of mental disorders. </p><p>Former child psychiatric patients as compared to controls had a significantly higher prevalence of all DSM-IV personality disorders (38.0 vs. 10.9 percent, p<0.001) and also a considerably higher personality disorder co-morbidity. They also had more psychosocial and environmental problems. This was exaggerated in those diagnosed with a personality disorder. Major depression, disruptive disorders and substance use disorders at a young age were strong predictors for adult personality disorder.</p><p>Patients with an early onset major depression had more personality disorders and more deviant personality traits than those with a late onset. </p><p>Forensic psychiatric male patients diagnosed with a previous conduct disorder as compared to those without had more cluster B personality disorders, and more repeated violent criminality and mixed abuse. They also exhibited more deviant personality traits and higher psychopathy scores.</p><p>The instrument "Child and Adolescent Psychiatric Screening Inventory-Retrospect" had acceptable sensitivity and specificity for assessment of child psychiatric disorders. Subscales demonstrated good internal reliability (Crohnbach´s alpha = 0.76-0.93).</p><p>The results suggest that adult personality disturbances are prevalent in individuals affected with mental problems at young ages. A better understanding of the transition of psychopathology from childhood to adulthood and a better identification of those at risk will be of help in attempts to prevent permanent impact on the adult personality.</p>

The familial aggregation of Major Depressive Disorder (MDD) has been repeatedly demonstrated. Several studies have investigated associations between various clinical characteristics of MDD in probands and overall rates of MDD in relatives. Few studies, however, have considered the familial aggregation of clinical characteristics of MDD. The aim of the present report is to examine mother–offspring associations of a variety of clinical characteristics of MDD in a general population sample. Data were derived from baseline and 4-year-follow-up data of 933 adolescents and their biological mothers of the Early Developmental Stages of Psychopathology (EDSP) study, a prospective-longitudinal community study. MDD and its characteristics were assessed with the Munich-Composite International Diagnostic Interview. We found that children of mothers who had a lifetime history of severe MDD and high number of symptoms, high impairment and/or melancholia, revealed elevated odds of MDD regarding the same characteristics as their mothers (ORs between 5.2 and 13.9). The observed associations did not differ by the children’s sex. DSM-IV melancholia and severity as well as impairment were found to aggregate within families. This finding can be interpreted as a validation of the DSM-IV MDD severity subtypes as well as of the melancholic specifier. Severe and melancholic MDD reveal a considerable high degree of familiar aggregation making the search for mechanisms involved in the familiar transmission of these forms of MDD particularly promising.