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M.A. / Irritable bowel syndrome has the dubious honour of being one of the most widely researched, yet poorly understood gastrointestinal disorders. Vast amounts of research have been conducted into every facet of this disorder, yet the investigations yield results that are often contradictory and more conducive to complication than clarification. In light of the quote above, it becomes apparent that research into IBS has fulfilled the requirements for 'serious research', leaving medical practitioners and researchers with more questions than answers. Irritable bowel syndrome is a bowel disorder characterised by abdominal pain and either diarrhoea or constipation (Bennett, 1989). It is estimated to affect 8 to 15% of the population, and accounts for between 50% and 70% of referrals to gastroenterology clinics (Whitehead & Schuster, 1985). Such a common disorder should be well understood but it is not. In fact, there is little consensus amongst clinicians and researchers concerning the underlying cause of this syndrome. Organic causes which have been suggested include abnormal motor activity of the intestinal tract (Snape et al., 1976), abnormal gut hormone secretion and sensitivity (Ritchie, 1973, in Lynn & Friedman, 1993) and diet (Jones et al., 1982, in Corney et al., 1991). Many studies have also indicated that psychological factors are important and that patients with this syndrome are more neurotic, depressed or anxious than others (Hislop, 1971; Young et al., 1976). Research findings have tended to be contradictory, yet one common thread throughout the literature has been the role that stress seems to play in both the onset and maintenance of IBS. A number of studies have been conducted in this area, yet once again the findings have been contradictory and little clarity has been achieved. It is against this background that the aims of the present study can be described. The aims of the present study are twofold. The first, and most specific aim is to clarify the relationship between psychological stress and IBS. In particular, the present investigation will explore the differences in daily and occupational stress between healthy individuals and those suffering from IBS. The second aim of this research more general, and concerns theory building. This is particularly important in a field where there has been so much ambiguity and confusion.

Circulating cell-free mitochondrial DNA (cf-mtDNA) is an emerging biomarker of psychobiological stress and disease which predicts mortality and is associated with various disease states. First, I present a systematic review of the literature that shows cf-mtDNA levels respond to common real-world stressors. The review discusses current knowledge on the mechanisms of cf-mtDNA release, its molecular forms of transport, potential physiological functions, cellular and neuroendocrine triggers, and factors that may contribute to cf-mtDNA removal from the circulation. Second, to evaluate the contribution of cf-mtDNA to health and disease states, standardized high-throughput procedures are needed to quantify cf-mtDNA in relevant biofluids. I describe the development of MitoQuicLy: Mitochondrial DNA Quantification in cell-free samples by Lysis. I demonstrate high agreement between MitoQuicLy and a commonly used column-based method, although MitoQuicLy is faster, cheaper, and requires a smaller input sample volume. I find that cf-mtDNA levels between concurrently collected plasma, serum, and saliva from the same individual differ on average by up to two orders of magnitude and are poorly correlated with one another, pointing to different cf-mtDNA biology or regulation between commonly used biofluids in clinical and research settings. Finally, I deploy MitoQuicLy in a highly phenotyped cohort of participants with mitochondrial disease and healthy controls to quantify the impact of a brief psychological stressor on cf-mtDNA levels in three biofluids and evaluate how cf-mtDNA release varies between individuals, biofluids, and mitochondrial disease status. These studies set the stage for a research agenda identifying novel links between psychological stress and physiological response, which may improve our understanding of how stressful experiences increase disease risk. In the future, cf-mtDNA release or its downstream effects may be targeted to modulate the impact of psychological stress on human health.

This empirical study assessed the perceived stressors in medical school environment and psychological outcomes in undergraduate medical students in a non - western sample. The sample consisted of African and Indian students in the Clinical group (N = 149) and a matched Control group, the Pre-clinical group (N = 158) bringing the total number of participants to 307. The research dealt with perceived stressors, coping mechanisms and outcomes in a medical school environment. Outcome was assessed using self-report instruments which examined stress symptoms and psychological distress. Both bivariate and multivariate correlational analyses were performed to investigate correlations and the predictive value of risk factors for psychological distress. The findings indicate that there are no significant differences in the perception of stressors in the medical school environment between the Pre-clinical and Clinical groups. Maladaptive coping strategies, perceived stressors and female gender have important roles to play in predicting psychological distress. High self-esteem and good social support for both groups, as well as optimism in the Clinical group protects against psychological distress. Strengths and limitations of this study as well as implications for intervention strategies among undergraduate medical students are also discussed. / Thesis (Ph.D.)-University of KwaZulu-Natal, 2003.

M.Sc.

Background: Sexual minority women (SMW; e.g., lesbian, bisexual women) are at substantially higher risk for hazardous drinking (HD) than their heterosexual, cisgender counterparts. There is considerable evidence that minority stressors at the individual (e.g., internalized stigma) and interpersonal (e.g., discrimination) levels are associated with HD among SMW, but minority stressors at the structural level (e.g., structural stigma) are understudied. Further, there is a wide gap in the literature on the relationships between multilevel minority stressors and HD. Additionally, there is evidence that these associations may differ by race/ethnicity and sexual identity, but relatively little is known about these differences, particularly in a multilevel context. Methods: This dissertation includes three studies that were guided by an adaptation of the minority stress model and the social ecological model. In the first study we conducted a systematic review of quantitative research studies that examined associations between structural stigma and alcohol-related outcomes among sexual and gender minority (SGM) adults in the United States. In the second study we used data from a diverse sample of SMW enrolled in the Chicago Health and Life Experiences of Women (CHLEW) study to determine whether structural stigma at Wave 4 (2017-2019) was prospectively associated with HD at Wave 5 (2019-2022), and whether this association was attenuated when accounting for individual- (i.e., internalized stigma, stigma consciousness) and interpersonal- (i.e., discrimination, sexual identity concealment) level minority stressors. In the third study we used data from Waves 4 and 5 of the CHLEW study to examine whether associations between multilevel minority stressors (i.e., internalized stigma, stigma consciousness, discrimination, sexual identity concealment, structural stigma) and HD varied by race/ethnicity and sexual identity. Results: The systematic review included 11 studies. There was moderate to strong support for a positive association between structural stigma and poor alcohol-related outcomes among SGM people, with differences by gender, sexual identity, race, and ethnicity. All studies used cross-sectional designs, and nearly half utilized non-probability samples. Transgender and nonbinary people, SGM people of color, and sexual identity subgroups beyond gay, lesbian, and heterosexual were underrepresented. Multilevel stigma and resiliency factors were understudied. In the second study, structural stigma was positively associated with HD alone, and when combined with interpersonal-level minority stressors. With the addition of individual-level minority stressors, the association between structural stigma and HD was attenuated, with partial attenuation (i.e., structural stigma was still significant) in the model combining all three levels, and full attenuation (i.e., structural stigma was no longer significant) in the model with only structural stigma and individual-level stressors. Discrimination was negatively associated with HD in the fully combined model and was not associated with HD in any other models. In the third study, we found that associations between structural stigma and HD did not vary by race/ethnicity or sexual identity. However, the associations between individual-level minority stressors (i.e., internalized stigma, stigma consciousness) and interpersonal-level minority stressors (i.e., sexual identity concealment) with HD varied somewhat by race/ethnicity and sexual identity. Conclusions: Findings from this dissertation highlight the importance of structural stigma in SMW’s HD and underscore the importance of both structural-level and multilevel minority stressors in designing interventions to effectively address HD drinking disparities and inequities among SMW. Future research is needed using intersectional approaches with probability samples, longitudinal designs, expanded measures of structural stigma, and samples that reflect the diversity of SGM people.