A Dissertation submitted to the Faculty of Medicine in part fulfilment of the requirements for the Degree of Master of Medicine in Psychiatry at the University of the Witwatersrand. / The motivation for undertaking this study stems from the confusion that reigns in the literature regarding the relationship between personality, personality traits and dysthymic disorder. A large body of theorists ancl researchers still claim a definite association between dysthymia and personality. Their views arose to an extent from the concept of dysthymia as it developed through the past few decades. Dysthymia grew out of the concept of depressive neurosis which had a stronger basis in personality pathology. other terms like neurotic depression and depressive reaction preceded depressive neurosis. with the advent of DSM-III and DSM-III-R, dysthymia was moved from the neuroses to the mood disorders category. The DSM-IV Mood Disorders Work Group has also reinforced the classification of dysthymia with mood disorders. The Work Group has embarked on research to determine the symptomatology that should be used for the diagnosis of dysthymia. It is proposed that cognitive, functional and vegetative symptoms be included in DSM-IV to further entrench dysthymia as an affective disorder and extricate it from the personality disorders. / Andrew Chakane 2018

For complex traits, population genetic studies ask: to what extent do genetic variation and environmental variation influence, determine and predict phenotypic variation? More specifically, researchers ask two questions. First, how much of the phenotypic variation is genetic in origin? Second, if the genetic component of a trait has been ascertained, then by what mechanisms do the causal variants contribute to the genetic variation that impacts on the phenotype? Previous studies have indicated a polygenic structure for many complex traits, which means that the genetic variation in those traits is the result of the cumulative effect from hundreds or even thousands of genetic variants. To further decipher the polygenic genetic architecture of a complex trait, genetic studies aim to identify the number, the location in the genome, and the distribution of the effect sizes of causal variants, as well as their individual and interacting effects. Linkage analysis and genome-wide association studies (GWAS), either based on single variants or sets of variants categorized by functional annotations, can be applied to map the potentially causal variants in the genome. The identification of disease-associated loci, however, is only the starting point in identifying causal variants. Causal variants are usually difficult to distinguish from the large number of variants in linkage disequilibrium (LD) within the associated loci, and may be in incomplete LD with genotyped variants. Computational prediction integrated with multi-level ‘Omic’ data will help the prioritization of candidate causal variants, which then become important targets for experimental validation (Chapter 1). Major depressive disorder (MDD) is a complex trait, contributes the second most important burden to global disease. Both genetic and environmental components have been suggested for this disorder in previous studies, although a clear partitioning of the contribution of each component and the identification of major contributing components is yet to be achieved. In efforts to map causal genetic variants, genome-wide association studies of MDD have identified few significant associations so far. The polygenic architecture combined with the widespread clinical and genetic heterogeneity of MDD between populations may impede the identification of causal variants (Chapter 2). In this thesis, I will present three studies; the first study estimated the proportions of the phenotypic variation that are genetic or familial environmental in origin in two depression definitions(chapter 3), followed by two studies where distinct (non- GWAS) methods were used to identify candidate causal genetic variants for MDD (chapter 4,5). In detail, in chapter 3, a variance component analysis was applied to GS:SFHS (Generation Scotland: Scottish Family Health Study) to investigate the relative genetic and environmental contributions to diagnosed major depressive disorder (MDD) and self-declared depression (SDD). Models for MDD and SDD that simultaneously included genetic and environmental effects suggested that narrow-sense heritability could be inflated by the environments shared by nuclear family members. The most parsimonious models selected for both MDD and SDD included SNP and pedigree-associated genetic effects and the effect of the common environment of couples. In chapter 4, I integrated pathway analysis and multi-level regional heritability analyses in a pipeline designed to identify MDD-associated pathways. The pipeline was applied to two independent GWAS studies (GS:SFHS and PGC1-MDD). The NETRIN1 signalling pathway showed the most consistent association with MDD across the two samples. Polygenic risk scores (PRSs) from this pathway showed predictive accuracy better than whole-genome PRSs when using AUC statistics, logistic regression and the linear mixed model. In chapter 5, genome-wide Haplotype-block-based regional heritability mapping (HRHM) was applied to identify haplotype blocks significantly contributing to MDD. A haplotype block across a 24kb region within the TOX2 gene reached genotype-wide significance in GS:SFHS. Single-SNP and haplotype based association tests were used to localize the association signal within the region identified by HRHM, and demonstrated that five out of nine genotyped SNPs and two haplotypes were significantly associated with MDD. The results were replicated in the UK-Ireland group in PGC2-MDD. The brain expression of TOX2 and brain-specific LncRNA RP1-269M15.3 were also significantly regulated by MDD-associated SNPs within the identified haplotype block. The three studies highlight the value of the application of multiple population genetics and bioinformatics methods to multiple family-based and population-based cohorts in identification of risk factors for MDD.

Diss. Univ. Zürich, 2003. / Online-Datei+Arbeitsbericht (17 Bl.)+die einzelnen Seiten der Homepage in ausgedruckter Form.

The study was based on the clinical data summaries ("item sheets") of children who attended the Maudsley Hospital during the late 1960s and early 1970s. These summaries were used to identify a group of 80 child and adolescent psychiatric patients with an operationally defined depressive syndrome. The depressed children were individually matched with 80 non-depressed psychiatric controls on demographic variables and non-depressive childhood symptoms by a computer algorithm. At follow-up, on average 18 years after the initial contact, information was obtained on the adult psychiatric status of 82% of the total sample. Adult assessments were made "blind" to case/control status, and included standardized measures of "lifetime" psychiatric disorder and psychosocial functioning. The depressed group was at increased risk for affective disorder in adult life, and had elevated risks of psychiatric hospitalization and psychiatric treatment. Depressed children were no more likely than control children to have non-depressive adult psychiatric disorders. These findings suggest that there is substantial specificity in the continuity of affective disturbances between childhood and adult life.

Thesis (doctoral)--University of Uppsala, 1981. / Bibliography: p. 47-56.

Thesis (M.S.)--University of Wisconsin--Madison, 1991. / Typescript. eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references (leaves 101-109).

No description available.

Major Depressive Disorder is a prevalent and pervasive problem in the United States, and this mental disorder disproportionately affects adolescents of color. In particular, there is little research understanding how Hispanic/Latinx adolescents utilize and engage with mental health services, such as psychotherapy, to reduce their symptoms of depression, including factors that are positively and negatively related to engagement. As such, the aims of this study were to understand whether there were any relationships between presenting characteristics of adolescents seeking therapy for depression and their subsequent engagement with therapeutic services, with a focus on analyses examining trends in Hispanic/Latinx adolescents. To investigate these aims, we utilized data from a pilot study in which adolescents (n=42) received a mind-body intervention for depression called Mind-Body Skills Groups. We examined possible relationships between depression severity, age, Hispanic/Latinx background, and their interactions with engagement, as measured by attendance rates, self-reported motivation, and at-home skills practice. We hypothesized that high depression severity, high age, and being Hispanic/Latinx would all negatively influence engagement; we also hypothesized the depression-engagement and age-engagement relationships would be moderated by Hispanic/Latinx background. Results revealed initial relationships between lower age and being Hispanic/Latinx with higher attendance rates; depression severity was not related to attendance. When these relationships were further analyzed using hierarchical regression, no significant relationships between predictor and outcomes variables, as well as their interactions, were discovered. In an exploratory analysis investigating factors of adolescent depression using subscales, greater interpersonal problems predicted higher attendance rates. Results are interpreted relative to limitations of the small sample size and possible measurement concerns within this study, including a discussion of possible ways to improve related studies on Hispanic/Latinx youth in the future.

Thesis (Ph.D. in Epidemiology) -- University of Colorado Denver, 2008. / Typescript. Includes bibliographical references (leaves 103-109). Free to UCD Anschutz Medical Campus. Online version available via ProQuest Digital Dissertations;

Carisbamate (CRS) and lamotrigine (LTG) are anticonvulsants which act mainly on neuronal voltage-gated sodium channels, that have been shown to have antidepressant-like effects in animal models of depression. In vivo electrophysiological recordings were carried out following 2 and 14 days of CRS or LTG administration. Overall firing activity in the dorsal raphe, locus coeruleus and ventral tegmental area were decreased with CRS. Similarly, a decrease in the dorsal raphe was also observed with LTG. Despite these presynaptic decreases in firing activity, both anticonvulsants exhibited significant enhancement of serotonergic transmission in the hippocampus as demonstrated by increased tonic activation of postsynaptic 5-HT1A receptors. This may be attributed to the observed desensitization of the terminal 5-HT1B autoreceptors. This study suggests that the enhanced serotonergic effect may be associated with an antiglutamatergic effect, and may contribute to the antidepressant-like effect of CRS in the forced swim test and the antidepressant properties of LTG.