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The human cerebral cortex, the outermost layer of the brain, is typically considered in imaging studies to consist of grey matter (GM), with white matter (WM) lying below it. With better imaging techniques, a third tissue type, found between GM and WM, can be identified. This layer contains myelinated axons and is found in the cortex, thus we call it intracortical myelin (ICM), or myelinated grey matter (GMm). We examined the cortical thickness measurements in female patients with bipolar I or II disorders (BD) versus healthy controls. Previous studies have only examined the thickness of the entire cortex, the GM. We developed a processing pipeline and a statistical tool for examining the ICM thickness between two groups. Results show that there are potential differences in GMm between BD and control groups. Further regional and statistical analysis is required to identify the regions of greatest difference, and to confirm significant differences between BD and control groups. / Thesis / Master of Science (MSc)

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Despite an abundance of older and more recent retrospective and considerably fewer prospective-longitudinal studies in bipolar disorders I and II, there are still remarkable deficits with regard to our knowledge about the natural course and burden. The considerable general and diagnosis-specific challenges posed by the nature of bipolar disorders are specified, highlighting in particular problems in diagnostic and symptom assessment, shifts in diagnostic conventions and the broadening of the diagnostic concept by including bipolar spectrum disorders. As a consequence it still remains difficult to agree on several core features of bipolar disorders, such as when they begin, how many remit spontaneously and how many take a chronic course. On the basis of clinical and epidemiological findings this paper summarizes (i) a significant need to extend the study of the natural course of bipolar disorder in clinical samples beyond the snapshot of acute episodes to the study of the mid-term and long-term symptom course, associated comorbidities and the associated burden of the disease. (ii) In terms of epidemiological studies, that are also of key importance for resolving the critical issues of threshold definitions in the context of the bipolar spectrum concept, there is a clear need for identifying the most relevant risk factors for the first onset and those for the further illness progression in early stages. Since there are some indications that these critical processes might start as early as adolescence, such studies might concentrate on young cohorts and clearly before these prospective patients come to clinical attention. (iii) The value of both types of studies might be enhanced, if beyond the use of standardized diagnostic interview, special attempts are made to use prospective life- and episode-charting methods for bipolar illnesses.

Bipolar disorder is a relatively common form of mental illness that depends strongly on genetic inheritance for expression. The author of this study has sought to evaluate whether the gender of subjects influences which genetic variants are associated with the disease. A portion of the cases from a previously published study were analyzed using PLINK software and the association of single-nucleotide polymorphisms was evaluated separately for all cases, for female subjects alone, and for male subjects alone. The results obtained for male subjects alone reached higher levels of statistical significance than when both genders were evaluated together or when female subjects were evaluated alone. The most significantly scoring polymorphisms were distinctly different for the 2 genders. In particular, a site downstream of the ion exchanger SLC24A3 and upstream of the Rab5-interacting protein RIN2 gene on chromosome 20 (rs6046396) yielded very high significance in men (p=3.91 X 10-9).

This thesis presents research investigating the relationship between, and methods of, measuring circadian rhythms in mood disorders in a population of currently depressed and euthymic individuals with both depression and bipolar disorder. This was first assessed by comparing group differences in subjective sleep and circadian measures with objective sleep and circadian measures. The objective circadian measures involved actigraphy and melatonin profiling. This analysis showed group differences in subjective sleep and circadian parameters compared to controls, however no robust differences between mood groups. Objective melatonin profiling showed a mild agreement with subjective circadian parameters. Next, we studied the external validity of a subjective rating scale measuring biological rhythm disturbance, the Biological Rhythms Interview for Assessment in Neuropsychiatry (BRIAN), against objective measures of sleep and circadian activity rhythmicity. The BRIAN demonstrated some promising external validity, namely correlations with wake after sleep onset (WASO) and sleep efficiency, as well as melatonin levels in each group. These studies provide evidence of the extent to which a self-report may help in assessing parameters of sleep and circadian rhythms in the clinical setting. In doing so, it is expected that the use of subjective ratings will provide insight into the impact of biological rhythms disturbances and mood disorders. Lastly, we conducted an overview of the preclinical and clinical literature investigating the impact of circadian disturbance on cognitive performance. The results from this literature review yielded patterns of rhythmicity in specific parameters in each of the attention, memory, and executive function domains in humans, whereas attention and memory are more of a primary focus in animal studies. However, we also found that there are significant gaps in the understanding of how disturbances in circadian rhythms may influence cognitive function. This review also highlights the importance of cross-species translational validity from a methodological perspective, in order to generate positive clinical results beginning at the preclinical stage in neuropsychiatric disorders. / Thesis / Master of Science (MSc)

In this thesis I set out to show that the bioethical literature concerning the treatment of chronic suicidal ideation occupies a serious omission: it does not discuss the critical function that self-trust serves in the recovery process. Self-trust is a core component of autonomy, and therefore plays a pivotal role in the shaping of one’s sense of self and his or her capacity to effectively engage in therapeutic interventions. I begin by discussing the relationship between agency and self-trust, and how this influences one’s ability to make decisions and self-advocate. Secondly, I evaluate how self-trust relates to aspects of the suicidal mind, including existential distress and negative urgency. Finally, I will offer recommendations as to how the explicit (re-) development of self-trust skills can significantly enhance the effectiveness and timeliness of contemporary dialectical treatment practices. / Thesis / Master of Arts (MA)

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