Browsing Doctoral Degrees (Psychiatry) by Subject "Associated adenylate cyclase activating polypeptide 1 (ADCYAP1)"
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- ItemEpigenomic analysis of posttraumatic stress disorder in female rape survivors in South Africa(Stellenbosch : Stellenbosch University, 2021-03) Nothling, Jani; Hemmings, Sian M. J.; Seedat, Soraya, 1966-; Abrahaams, Naeema; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Psychiatry.ENGLISH SUMMARY : Compared to other trauma types, rape is associated with a high risk of developing posttraumatic stress disorder (PTSD). Women are at increased risk of developing PTSD compared to men and are also more frequently victims of sexual assault. PTSD is a complex, multifactorial disorder and an array of demographic, trauma-related, psychological and genetic putative risk and protective factors mediate or contribute to the development and course of the disorder. Few studies have comprehensively investigated demographic and psychological risk and protective factors for PTSD in a longitudinal prospective design, especially beyond the 3-month post-rape period and in low- to medium-income countries. There are currently no known epigenome-wide association studies (EWASs) investigating differential methylation in relation to PTSD in (1) an African population and (2) a sample of rape-exposed women exclusively. There are also no known studies investigating longitudinal change in the hypothalamic-pituitary-adrenal (HPA) axis associated candidate gene FK506 binding protein (FKBP5) in relation to PTSD in a sample of rape-exposed women exclusively. In this study we investigated the demographic, rape/assault-related, psychological, genetic (FKBP5) and epigenetic (epigenome-wide differential methylation) risk and protective factors associated with the development and course of PTSD symptoms over six months. Self-report measures and specimen collection was completed at baseline (within 20 day after the rape), 3-months and 6-months post-rape as part of the Rape Impact Cohort Evaluation (RICE) study. The RICE sample consisted of 852 Black African rape-exposed women, between the ages of 16 and 40 years and from a low socio-economic background. We found that baseline demographic, rape/assault-related and psychological protective factors were not significant predictors of PTSD symptoms over time. Baseline depression and rape stigma were significant psychological risk factors for the development and course of PTSD post-rape. We also identified one intergenic CpG site (cg01700569) that was differentially methylated in relation to PTSD status at 3-months post-rape on a genome-wide level. Thirty-four differentially methylated regions were identified and included a region in the HPA-axis-associated adenylate cyclase activating polypeptide 1 (ADCYAP1) gene and the neuroendocrine-associated brain-specific serine/threonine-protein kinase 2 (BRSK2) gene. Decreased BRSK2 and ADCYAP1 methylation at 3-months and 6-months post-rape was associated with increased PTSD symptom scores at the same time-points. Decreased FKBP5 methylation was a predictor of increased PTSD symptom scores at 3-months and 6-months post-rape. High childhood trauma and the CC genotype of FKBP5 rs1360780 resulted in decreased FKBP5 methylation and increased PTSD scores at baseline. The study builds on existing literature, highlighting the psychological risk factors for the development and course of PTSD in rape-exposed women. Methylation findings also build on the existing literature regarding the role of epigenetics in PTSD, although the genome-wide finding implicating differential methylation of BRSK2 in the development of PTSD is a novel finding in human studies. The study provides evidence that both psychological and biological factors have an impact on the symptom trajectory of PTSD and that both should be considered when designing and implementing interventions for the treatment of PTSD post-rape.