Browsing Doctoral Degrees (Psychiatry) by Author "Kalungi, Allan"
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- ItemInternalizing mental disorders in HIV : the role of environment, telomere length and selected genetic variants(Stellenbosch : Stellenbosch University, 2020-03) Kalungi, Allan; Hemmings, Sian M. J.; Kinyanda, Eugene; Seedat, Soraya, 1966-; Womersley, Jacqueline S.; Joloba, Moses; Stellenbosch University. Faculty of Medicine and Health Sciences. Dept. of Psychiatry.ENGLISH SUMMARY : Background: HIV+ children and adolescents (CA-HIV) suffer from a considerable burden of internalizing mental disorders (IMDs), which are associated with negative outcomes, such as poor academic functioning and faster HIV disease progression. IMDs are complex disorders with unknown etiology, despite significant research efforts. This PhD study aimed to investigate whether acute stress interacts with vulnerability factors (genetic, acquired or a combination of both) to influence the occurrence of IMDs. Methods: The study used data from 736 Ugandan CA-HIV who were recruited into a larger study examining mental health among children and adolescents living with HIV/AIDS in Kampala and Masaka districts of Uganda (CHAKA Study). Cases (n = 368) were CA-HIV who had any internalizing mental disorder (IMD) (depressive disorders, anxiety disorders and PTSD). Controls (n = 368) were CA-HIV who did not have these disorders and were matched with cases on age, site, socio-economic status and sex. Psychiatric disorders were assessed using the Child and Adolescent Symptom Inventory-5 (CASI-5) and the Youth Inventory-4R. Chronic and acute stress classes were determined by hierarchical cluster analysis using an index derived from data on social disadvantage variables. DNA extracted from blood was used for targeted genetic investigations. Specifically, variants in the serotonin transporter gene (SLC6A4: 5-HTTLPR, rs25531, 5-HTTLPR/rs25531 and STin2 VNTR), and tryptophan hydroxylase gene (TPH2: (rs1843809, rs1386494, rs4570625 and rs345177220) were determined. Relative telomere length (TL) was also determined using these samples. Statistical analysis: Socio-demographic variables were compared between cases and controls. Linear regression was used to determine the association between TL and IMDs. Logistic regression was used to: i) determine the association between acute stress and IMDs, and ii) assess the moderating effect of each of the vulnerability factors on the associations identified in (i). Results: Presence of IMDs was associated with accelerated TL attrition over a 12-month period. The T-allele of TERT rs2736100 and the C-allele of TERC rs16847897 were associated with accelerated TL attrition among cases of IMDs (p = 0.007 and p = 0.012, respectively). CA-HIV who experienced severe acute stress were twice as likely to have an IMD compared to CA-HIV who experienced mild acute stress (p = 0.001). Acute stress significantly interacted with chronic stress (p = 0.033) and 5-HTTLPR/rs25531 haplotype (p = 0.049) to influence the likelihood of having an IMD. CA-HIV who experienced severe acute stress and severe chronic stress were four times more likely to be a case of IMDs as compared to those under mild acute stress and mild chronic stress. CA-HIV who possessed the S-A-S-A haplotype and experienced moderate or severe acute stress were respectively fifteen and twelve times more likely to be diagnosed with an IMD compared to CA-HIV who possessed the L-A-L-A haplotype and experienced mild acute stress. Conclusions: IMDs were associated with accelerated TL attrition. Severe chronic stress and 5-HTTLPR/rs25531 haplotype independently interacted with acute stress to increase risk for IMDs among Ugandan CA-HIV. These data support previously identified relationships between IMDs and accelerated biological aging, and provide evidence for the role of serotonin gene-environment interactions in the risk of developing IMDs among CA-HIV in Uganda.