Internalizing Mental Disorders and Accelerated Cellular Aging Among Perinatally HIV-Infected Youth in Uganda

Abstract

Introduction: Internalizing mental disorders (IMDs) in HIV+ children and adolescents are associated with impaired quality of life and non-adherence to anti-retroviral treatment. Telomere length is a biomarker of cellular aging, and shorter telomere length has been associated with IMDs. However, the nature of this association has yet to be elucidated. Objective: We determined the longitudinal association between IMDs and relative telomere length (rTL) and the influence of chronic stress among Ugandan perinatally HIV-infected youth (PHIY). Methods: IMDs (depressive disorders, anxiety disorders, and post-traumatic stress disorder) and IMDs were assessed using the locally adapted Child and Adolescent Symptom Inventory-5. In 368 PHIY with any IMD and 368 age- and sex-matched PHIY controls without any psychiatric disorder, rTL was assessed using quantitative polymerase chain reaction. Hierarchical cluster analysis was used to generate the three chronic stress classes (mild, moderate, and severe). t -tests were used to assess the difference between baseline and 12 month rTL and the mean difference in rTL between cases and controls both at baseline and at 12 months. Linear regression analysis was used to model the effects of chronic stress on the association between IMDs and rTL, controlling for age and sex. Results: We observed longer rTL among cases of IMDs compared with controls ( p < 0.001). We also observed a statistically significant reduction in rTL between baseline and 12 months in the combined sample of cases and controls ( p < 0.001). The same statistical difference was observed when cases and controls were individually analyzed ( p < 0.001). We found no significant difference in rTL between cases and controls at 12 months ( p = 0.117). We found no significant influence of chronic stress on the association between IMDs and rTL at both baseline and 12 months. Conclusion: rTL is longer among cases of IMDs compared with age- and sex-matched controls. We observed a significant attrition in rTL over 12 months, which seems to be driven by the presence of any IMDs. There is a need for future longitudinal and experimental studies to understand the mechanisms driving our findings.

TERT rs2736100 and TERC rs16847897 genotypes moderate the association between internalizing mental disorders and accelerated telomere length attrition among HIV+ children and adolescents in Uganda

“…For IMDs combined, rates of between 12 and 27% have been documented in Uganda and South Africa, respectively [ 1 , 9 ]. Among people living with HIV/AIDS, IMDs have been associated with a number of other negative outcomes, including accelerated cellular aging [ 10 ], faster HIV disease progression [ 11 , 12 ], poor adherence to medication [ 12 , 13 ], risky sexual behavior [ 13 , 14 ], poor linkage to care for newly diagnosed HIV+ persons [ 15 ], increased HIV transmission (through the promotion of HIV drug resistance) [ 16 ] and impaired academic and social functioning [ 13 ].…”

“…We previously found evidence to suggest accelerated TL attrition that was driven by IMDs among Ugandan HIV+ children and adolescents [ 10 ]. There is, however, a dearth of data on the mechanisms by which IMDs lead to TL attrition.…”

“…We have previously determined an association between IMDs and TL in a sample of Ugandan HIV+ children and adolescents [ 10 ]. Specifically, TL was significantly longer in IMDs cases at baseline but did not differ from control TL at 12-month follow-up, suggesting that TL shortening over the one-year period was greater in participants with IMDs.…”

“…Given that TERT and TERC are involved in TL maintenance [ 30 ], the present study investigated whether genetic variation in TERT (rs2736100, rs7726159, rs10069690 and rs2853669) and TERC (rs12696304, rs16847897 and rs10936599) moderated the association between IMDs and baseline and 12-month TL. Having observed that IMDs were driving accelerated TL attrition in the previous study [ 10 ], we modelled IMDs as the independent variable and TL as the dependent variable. We thus assessed for the interaction between IMDs and TERT and TERC on TL.…”

Chronic comorbidities in children and adolescents with perinatally acquired HIV infection in sub-Saharan Africa in the era of antiretroviral therapy

“…67 [67][68][69] It is possible that the neuropathological effects of HIV infection may augment risk. 70 Mental health disorders impact adherence to ART and are associated with an impaired quality of life, yet they typically receive little attention in the face of physical health concerns.…”