The biological mechanisms proposed to underlie primary mood disorder do not usually include a neuropathological component. Over recent years, a significant imaging literature attests to structural abnormalities in various brain regions in mood disorder, and has encouraged neuropathological investigations. Although the neuropathological understanding of mood disorder is still rudimentary, structural correlates have begun to emerge. The studies described in this thesis investigate the neuropathology of the anterior cingulate cortex in mood disorder. The anterior cingulate cortex is extremely diverse and complex, particularly in respect to its cytoarchitecture and functional organisation. These details are important when considering the precise localisation and clinical correlates of the neuropathological changes of this region in disease. Accordingly, I performed a detailed analysis of the cytoarchitecture of the human anterior cingulate cortex, as a prelude to investigations of this region in mood disorder. I measured several morphometric parameters within different anatomical levels and both hemispheres of the anterior cingulate cortex. Overall I found a clear distinction in the cellular composition of the supragenual and subgenual regions of the anterior cingulate cortex. The subgenual region demonstrated a lower glial density and smaller neurons in comparison to the supragenual region. A modest difference in neuronal density was also observed, with a higher density in the deep layers of the subgenual cortex compared to the deep layers of the supragenual cortex. Total cortical depth was also thinner in the subgenual region. This work may have important implications for the interpretation of imaging and pathological data in mood disorder. To assess the cytoarchitecture of this brain region in mood disorder, I examined several morphometric indices in addition to various parameters of gene expression in post mortem brains. I found a range of cytoarchitectural abnormalities in the supragenual anterior cingulate cortex in mood disorder. The most prominent change included a reduction in glial density, which was evident in all layers of the cortex. Glial fibrillary acidic protein was also reduced, providing some evidence for astrocyte involvement. Various neuronal changes were also observed in the mood disorder group. These included layer-specific reductions in pyramidal neuron density and a modest change in the density of cairetinin-immunoreactive neurons. I did not find any evidence supporting synaptic pathology in the anterior cingulate cortex in mood disorder. These findings extend previous evidence of cytoarchitectural alterations in the anterior cingulate cortex in mood disorder and in particular emphasise the prominent involvement of glial cells in the neuropathology of this disease. The origins of the glial (and neuronal) deficits in mood disorder remain to be established, but they are likely to have pathophysiological consequences.

The majority of adolescents diagnosed with Major Depressive Disorder (MDD) and admitted to a psychiatric hospital in Gauteng complained of being tired of 1'talk therapy" . This study used imagery as a technique in the treatment of two adolescents suffering from MDD. The initial identification was based on the results of the Beck Depression Inventory (BDI). After a number of sessions of implementing imagery techniques, the BDI was readministered. To determine the long-term effectiveness of imagery, the BDI was again administered a month-and-a-half after completion of the sessions. The results before and after indicate a reduction in the severity of depression. The results at the month-and-a-half follow-up session indicated a further reduction in the level of depression in both cases. This indicates the long-tenn effectiveness of imagery in treating depression. Further research is required, but there are significant indications that imagery may be an effective technique in the treatment of depressed adolescents under psychiatric supervision. / Educational studies / M.Ed (Guidance and Counseling)

Although the effects of both the menstrual and circadian cycles on mood have been well documented, the question of whether the two interact to influence mood has not yet been addressed, despite evidence for such an interaction on other variables. Blood sugar level is a major contributor to the mediation of mood and is easily regulated by dietary intervention; there is also evidence that it is influenced by both the menstrual and circadian cycles. The present research takes a positive psychological approach to managing mood; the aims were to identify where natural variations in mood occur in relation to its underlying physiology, taking an applied approach to suggest ways of effectively managing positive mood and maintaining psychological well-being. A series of studies was carried out to measure fluctuations in mood in relation to biological rhythms, and in response to cognitively demanding situations and simple interventions. Mood was measured throughout the research using the UWIST Mood Adjective Checklist. The most consistent results were in relation to the Energetic Arousal dimension. This was shown to be influenced by both the menstrual cycle and the time of day, as well as an interaction between these two factors, and was consistently related to changes in blood glucose levels. Energetic Arousal also appeared to be more sensitive to the effectsof the suggested interventions. Diurnal changes in mood throughout the course of a normal day were more evident among women in their premenstrual to menstrual phases, and also become more apparent in response to cognitive tasks. Trait Anxiety was a mediating factor in how individuals reacted to such tasks. Mood was closely related to blood glucose levels, and raising blood glucose to a robust but safe level effectivelyenhanced positive mood in cognitively demanding situations. Oral contraceptives generally tended to eliminate menstrual cycle-related effects on mood and responses to intervention. It was concluded that mood states among healthy women are influenced by a complex interplay between biological rhythms, physiological states, individual differences and the context in which these moods take place. Simple interventions that can easily be incorporated into one’s daily routine may be efficacious in maintaining a positive mood state, which has beneficial implications for psychological well-being.

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.

The majority of adolescents diagnosed with Major Depressive Disorder (MDD) and admitted to a psychiatric hospital in Gauteng complained of being tired of 1'talk therapy" . This study used imagery as a technique in the treatment of two adolescents suffering from MDD. The initial identification was based on the results of the Beck Depression Inventory (BDI). After a number of sessions of implementing imagery techniques, the BDI was readministered. To determine the long-term effectiveness of imagery, the BDI was again administered a month-and-a-half after completion of the sessions. The results before and after indicate a reduction in the severity of depression. The results at the month-and-a-half follow-up session indicated a further reduction in the level of depression in both cases. This indicates the long-tenn effectiveness of imagery in treating depression. Further research is required, but there are significant indications that imagery may be an effective technique in the treatment of depressed adolescents under psychiatric supervision. / Educational studies / M.Ed (Guidance and Counseling)

There is growing evidence to suggest that vascular disease plays an important role in late life depressive disorder. The aim of this study was to characterize vascular impairment in late life depression. Assessment of endothelial function, arterial stiffness, and atherosclerosis in a variety of vessel beds was carried out in 25 subjects with late life depression and 21 nondepressed control subjects. All study subjects underwent wave velocity, pulse wave analysis, carotid intima media thickness analysis, and magnetic resonance imaging of the brain and a subset gluteal fat biopsy and direct assessment of small artery endothelial function. There were no baseline differences in demographics or a range of vascular risk factors between the groups. There was a generalised vascular dysfunction in depressed subjects with significantly more atherosclerosis, poorer endothelial function and increased arterial stiffness. On neuroimaging, depressed subjects had significantly more dilated Virchow-Robin spaces in the basal ganglia. White matter lesion volumes in all regions were higher in depressed subjects but not significantly so. Furthermore, subjects with late onset depression (onset >60years) had greater vascular impairment when compared to those with early onset illness. Lastly, depressed subjects who did not respond to antidepressant monotherapy showed more vascular dysfunction compared to responders. The study has a number of limitations including the small sample size and as the study was cross sectional, the observed relationship between vascular dysfunction and depression is associative rather than causal. Further research in larger samples is required to address the methodological limitations of this study. If the study results are confirmed, the use of vasoprotective drugs to improve vascular function or retard atherosclerosis as diasease modifying agents in late life depression would be a rational development.

Cette thèse vise à mettre à l'épreuve les apports théoriques, dans un regard psycho-dynamique à partir d'un ancrage clinique et projectif, afin de comprendre le délicat tissage entre inscription temporelle et processus dans un travail d’articulation ; que propose le questionnement sur la perception des trois temps (passé, présent et futur), et de la spécificité d’inscription dans une situation non-figuratif au test du Rorschach, ainsi que processus d’enregistrement le récit au test du TAT. Si le caractère discontinu des évènements s'avère non structurant chez le déprimé anxieux, sur fond de la non continuité et de défaut de la permanence garanti par une relation objectale, à l'autre insuffisamment étayant, dont le psychisme se décompose dans la dépression anxieuse, revivre le passé et l'attente emporte souvent le sujet dans un abîme d'angoisse dans lequel il se perd. Ne pouvant plus s’ancrer dans le présent dans un mouvement d’élaboration et de symbolisation psychique, et, en miroir, engouffrant tout possible pour l'avenir, le sujet dit « déprimé anxieux » se retrouverait, paradoxalement, enfermé dans une impasse temporelle, se figure dans un spirale temporelle barré, sans écart qui potentialise son investissement pulsionnel, narcissique et objectal. / This thesis aims to test theoretical contributions in a psycho-dynamic look from a projective clinical anchorage and to understand the delicate weaving between time registration and work processes in a joint; proposed questioning the perception of the three times (past, present and future), and specific registration in a non-representational situation in the Rorschach test and the account registration process to test the TAT. If the discontinuous nature of the events proves not structured in anxious depressed, amid the non continuity and lack of permanence secured by a object relation, to the other supporting insufficiently whose psyche decomposes in anxious depression , relive the past and expectation often takes the subject into a abyss of anguish in which he loses. No longer able to anchor in this development in a movement and psychic symbolization, and, mirror, engulfing everything possible for the future, the subject says "anxious depressed" would end up, paradoxically, locked in a dead time if contained in a temporal barred spiral without gap which potentiates its instinctual investment, and object-narcissistic.

Text in English / The purpose of this study is to tell the story around the roles of relationships in the world of depressed women. The epistemological framework of this study is constructivism. This study involved a series of in-depth interviews with three depressed women who had young children. Hermeneutics was the method used to analyse the data. The stories of the participants were recounted through the researcher's lens in the form of themes that emerged. The specific ways each participant tried to cope, and the emerging processes from the researcher's perspective as to what she believed was helpful or unhelpful to the participants, in addition to what the participants themselves regarded as helpful, was discussed. Recurring themes evident in the stories of all three participants were elucidated in the story of the stories. The information gained could serve as guidelines to those working with depressed people from a Western and an African context. / Psychology / M.A. (Psychology)

Adolescent depression is a major public health problem, which is associated with educational problems, long-term psychiatric illness and suicide. One major source of stress during adolescence is peer rejection. In this thesis, I investigate the nature of the relationship between peer rejection and adolescent depression. In a review of longitudinal and experimental studies, I describe a bi-directional relationship between peer rejection and depressive symptoms. I then outline how genetic, cognitive and neural vulnerability may modify the effects of peer rejection on adolescent depression. Finally, I introduce five empirical chapters which test these hypotheses using different methodological approaches. The first study is a molecular genetic analysis of a sample of adolescents with and without a diagnosis of mood disorder. I report an interaction between diagnostic group, environmental stress (though not peer rejection specifically) and 5HTTLPR genotype on symptoms of anxiety, which supports the role of genetic factors in modifying the relationship between environmental stress and adolescent mood disorder. The second study is a behavioural study of negative attention biases in a typically developing sample of adolescents. I report a negative attention bias in adolescents with low (versus high) self-esteem. Although the data do not support a causal role for attention biases in adolescent depression, such biased cognitions could also moderate responses to peer rejection, maintaining affective symptoms. A final set of three fMRI datasets investigates how neural circuitry may influence depressed adolescents’ responses to peer rejection at three distinct stages: i) expectation of peer feedback, ii) the receipt of peer rejection, iii) emotion regulation of peer rejection. Data show distinct behavioural and neural differences between depressed patients and healthy controls during expectation and reappraisal of peer rejection, although heightened emotional reactivity immediately following the receipt of peer rejection did not differentiate behavioural or neural responses in adolescents with and without depression.

Text in English / The purpose of this study is to tell the story around the roles of relationships in the world of depressed women. The epistemological framework of this study is constructivism. This study involved a series of in-depth interviews with three depressed women who had young children. Hermeneutics was the method used to analyse the data. The stories of the participants were recounted through the researcher's lens in the form of themes that emerged. The specific ways each participant tried to cope, and the emerging processes from the researcher's perspective as to what she believed was helpful or unhelpful to the participants, in addition to what the participants themselves regarded as helpful, was discussed. Recurring themes evident in the stories of all three participants were elucidated in the story of the stories. The information gained could serve as guidelines to those working with depressed people from a Western and an African context. / Psychology / M.A. (Psychology)