Browsing by Author "Kinyanda, Eugene"

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    The 5-HTTLPR-rs25531 S-A-S-A haplotype and chronic stress moderate the association between acute stress and internalizing mental disorders among HIV+ children and adolescents in Uganda
    (Frontiers, 2021-04-23) Kalungi, Allan; Womersley, Jacqueline S.; Kinyanda, Eugene; Joloba, Moses L.; Ssembajjwe, Wilber; Nsubuga, Rebecca N.; Seedat, Soraya, 1966-; Hemmings, Sian M.
    Background: Internalizing mental disorders (IMDs) among HIV-positive (HIV+) children and adolescents are associated with poor disease outcomes, such as faster HIV disease progression. Although it has been suggested that the development of IMDs is moderated by interaction of stressful life events and vulnerability factors, the underlying etiology is largely unknown. Serotonin transporter gene [solute carrier family 6 member A4 (SLC6A4)] and human tryptophan hydroxylase 2 gene (TPH2) polymorphisms have been implicated in the development of IMDs. This study investigated the association between acute stress and IMDs, and moderation by chronic stress and genetic variants in SLC6A4 and TPH2. Hypothesis: Acute stress acts through genetic and environmental vulnerability factors to increase the risk of developing IMDs. Methods: Polymorphisms in SLC6A4 (5-HTTLPR, rs25531, 5-HTTLPR-rs25531, and STin2 VNTR) and TPH2 (rs1843809, rs1386494, rs4570625, and rs34517220) were genotyped in 368 HIV+ children and adolescents (aged 5–17 years) with any internalizing mental disorder (depression, anxiety disorders, or posttraumatic stress disorder), and 368 age- and sex-matched controls, who were also HIV+. Chronic and acute stress categories were derived by hierarchical cluster analysis. Logistic regression analysis was used to assess the independent moderating effect of chronic stress and each selected polymorphism on the association between acute stress and IMDs. Results: We observed a statistically significant association between severe acute stress and IMDs (p = 0.001). Children and adolescents who experienced severe acute stress were twice as likely to develop IMDs, compared to children and adolescents who experienced mild acute stress (p = 0.001). Chronic stress interacted with severe acute stress to increase the risk of IMDs (p = 0.033). Acute stress was found to interact with 5-HTTLPR-rs25531 S-A-S-A haplotype to increase the risk for IMDs among Ugandan HIV+ children and adolescents (p = 0.049). We found no evidence for a combined interaction of acute stress, chronic stress, and 5-HTTLPR-rs25531 on IMDs. Conclusion: The odds of having an internalizing mental disorder (IMD) were higher among HIV+ children and adolescents who experienced severe acute stress compared to HIV+ children and adolescents who experienced mild acute stress. Chronic stress and 5-HTTLPR-rs25531 independently moderated the association between acute stress and IMDs.
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    Agreement and discrepancy on emotional and behavioral problems between caregivers and HIV-infected children and adolescents from Uganda
    (Frontiers Media, 2019) Van den Heuvel, Leigh L.; Levin, Jonathan; Mpango, Richard S.; Gadow, Kenneth D.; Patel, Vikram; Nachega, Jean B.; Seedat, Soraya; Kinyanda, Eugene
    Background: HIV-infected children and adolescents (CA-HIV) face significant mental health challenges related to a broad range of biological and psychosocial factors. Data are scarce on the agreement and discrepancy between caregivers and CA-HIV regarding emotional and behavioral problems (EBPs) in CA-HIV. Objectives: We determined agreement between self- versus caregiver- reported EBPs and describe factors associated with informant discrepancy among caregiver–youth dyads who participated in the “Mental health among HIV-infected CHildren and Adolescents in KAmpala and Masaka, Uganda” (CHAKA) study. Methods: In a cross-sectional sample, caregiver-reported EBPs were assessed with the Child and Adolescent Symptom Inventory-5 (CASI-5), and self-reported problems were evaluated with the Youth Inventory-4 (YI-4) in 469 adolescents aged 12–17 years and the Child Inventory-4 (CI-4) in 493 children aged 8–11 years. Adolescents were questioned about experiences of HIV stigma. Caregiver psychological distress was assessed with the Self-Reporting Questionnaire (SRQ-20). Linear regression models were applied to identify variables associated with discrepancy scores. Results: Self-reported emotional problems (EPs) were present in 28.8% of adolescents and 36.9% of children, and 14.5% of adolescents self-reported behavioral problems (BPs). There was only a modest correlation (r ≤ 0.29) between caregiver- and CA-HIVreported EBPs, with caregivers reporting more EPs whereas adolescents reported more BPs. Informant discrepancy between adolescents and caregivers for BPs was associated with adolescent age and caregiver’s employment and HIV status. Among adolescents, EP discrepancy scores were associated with adolescent’s WHO HIV clinical stage, caregiver level of education, and caregivers caring for other children. Among children, EP discrepancy scores were associated with child and caregiver age, caregiver level of education, and caregiver self-rated health status. HIV stigma and caregiver psychological distress were also associated with discrepancy, such that adolescents who experienced HIV stigma rated their EPs as more severe than their caregivers did and caregivers with increased psychological distress rated EBPs as more severe than CA-HIV self-rated. Conclusions: EBPs are frequently endorsed by CA-HIV, and agreement between informants is modest. Informant discrepancy is related to unique psychosocial and HIVrelated factors. Multi-informant reports enhance the evaluation of CA-HIV and informant discrepancies can provide additional insights into the mental health of CA-HIV.
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    Association between serotonin transporter gene polymorphisms and increased suicidal risk among HIV positive patients in Uganda
    (BioMed Central, 2017-07-25) Kalungi, Allan; Seedat, Soraya; Hemmings, Sian M. J.; Van der Merwe, Lize; Joloba, Moses L.; Nanteza, Ann; Nakassujja, Noeline; Birabwa, Harriet; Serwanga, Jennifer; Kaleebu, Pontiano; Kinyanda, Eugene
    Background: Persons living with HIV/AIDS (PLWHA) are at an increased risk of suicide. Increased suicidal risk is a predictor of future attempted and completed suicides and has been associated with poor quality of life and poor adherence with antiretroviral therapy. Clinical risk factors have low predictive value for suicide, hence the interest in potential neurobiological correlates and specific heritable markers of suicide vulnerability. The serotonin transporter gene has previously been implicated in the aetiology of increased suicidal risk in non-HIV infected study populations and its variations may provide a platform for identifying genetic risk for suicidality among PLWHA. The present cross-sectional study aimed at identifying two common genetic variants of the serotonin transporter gene and their association with increased suicidal risk among human immunodeficiency virus (HIV)-positive adults in Uganda. Results: The prevalence of increased suicidal risk (defined as moderate to high risk suicidality on the suicidality module of the Mini Neuropsychiatric Interview (M.I.N.I) was 3.3% (95% CI, 2.0–5.3). The 5-HTTLPR was found to be associated with increased suicidal risk before Bonferroni correction (p-value = 0.0174). A protective effect on increased suicidal risk was found for the 5-HTTLPR/rs25531 S A allele (p-value = 0.0046)- which directs reduced expression of the serotonin transporter gene (5-HTT). Conclusion: The S A allele at the 5-HTTLPR/rs25531 locus is associated with increased suicidal risk among Ugandan PLWHA. Further studies are needed to validate this finding in Ugandan and other sub-Saharan samples.
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    Internalizing mental disorders and accelerated cellular aging among perinatally HIV-infected youth in Uganda
    (Frontiers Media, 2019) Kalungi, Allan; Womersley, Jacqueline S.; Kinyanda, Eugene; Joloba, Moses L.; Ssembajjwe, Wilber; Nsubuga, Rebecca N.; Levin, Jonathan; Kaleebu, Pontiano; Kidd, Martin; Seedat, Soraya, 1966-; Hemmings, Sian M. J.
    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.
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    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
    (BMC (part of Springer Nature), 2021-01-06) Kalungi, Allan; Kinyanda, Eugene; Womersley, Jacqueline S.; Joloba, Moses L.; Ssembajjwe, Wilber; Nsubuga, Rebecca N.; Kaleebu, Pontiano; Levin, Jonathan; Kidd, Martin; Seedat, Soraya; Hemmings, Sian M. J.
    Background: Internalizing mental disorders (IMDs) (depression, anxiety and post-traumatic stress disorder) have been associated with accelerated telomere length (TL) attrition; however, this association has not been investigated in the context of genetic variation that has been found to influence TL. We have previously reported an association between IMDs and accelerated TL attrition among Ugandan HIV+ children and adolescents. This study investigated the moderating effects of selected single nucleotide polymorphisms in the telomerase reverse transcriptase gene (TERT) (rs2736100, rs7726159, rs10069690 and rs2853669) and the telomerase RNA component gene (TERC) (rs12696304, rs16847897 and rs10936599) on the association between IMDs and TL, among Ugandan HIV+ children (aged 5–11 years) and adolescents (aged 12–17 years). Results: We found no significant interaction between IMDs as a group and any of the selected SNPs on TL at baseline. We observed significant interactions of IMDs with TERT rs2736100 (p = 0.007) and TERC rs16847897 (p = 0.012), respectively, on TL at 12 months. Conclusions: TERT rs2736100 and TERC rs16847897 moderate the association between IMDs and TL among Ugandan HIV+ children and adolescents at 12 months. Understanding the nature of this association may shed light on the pathophysiological mechanisms underlying advanced cellular aging in IMDs.
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    Validation of brief screening tools for depressive and alcohol use disorders among TB and HIV patients in primary care in Zambia
    (BioMed Central, 2011-05-04) Chishinga, Nathaniel; Kinyanda, Eugene; Weiss, Helen A.; Patel, Vikram; Ayles, Helen; Seedat, Soraya
    This study was conducted to evaluate the diagnostic accuracy and determine the optimum cut-off scores for clinical use of the Center for Epidemiological Studies Depression scale (CES-D) and Alcohol Use Disorders Identification Test (AUDIT) against a reference psychiatric diagnostic interview, in TB and anti-retroviral therapy (ART) patients in primary care in Zambia. Methods. This was a cross-sectional study in 16 primary level care clinics. Consecutive sampling was used to select 649 participants who started TB treatment or ART in the preceding month. Participants were first interviewed using the CES-D and AUDIT, and subsequently with a psychiatric diagnostic interview for current major depressive disorder (MDD) and alcohol use disorders (AUDs) using the Mini-International Neuropsychiatric Interview (MINI). The diagnostic accuracy was calculated using the Area Under the Receiver Operating Characteristic curve (AUROC). The optimum cut-off scores for clinical use were calculated using sensitivity and positive predictive value (PPV). Results. The CES-D and AUDIT had high internal consistency (Cronbach's alpha = 0.84; 0.98 respectively). Confirmatory factor analysis showed that the four-factor CES-D model was not a good fit for the data (Tucker-Lewis Fit Index (TLI) = 0.86; standardized root-mean square residual (SRMR) = 0.06) while the two-factor AUDIT model fitted the data well (TFI = 0.99; SRMR = 0.04). Both the CES-D and AUDIT demonstrated good discriminatory ability in detecting MINI-defined current MDDs and AUDs (AUROC for CES-D = 0.78; AUDIT = 0.98 for women and 0.75 for men). The optimum CES-D cut-off score in screening for current MDD was 22 (sensitivity 73%, PPV 76%) while that of the AUDIT in screening for AUD was 24 for women (sensitivity 60%, PPV 60%), and 20 for men (sensitivity 55%, PPV 50%). Conclusions. The CES-D and AUDIT showed high discriminatory ability in measuring MINI-defined current MDD and AUD respectively. They are suitable mental health screening tools for use among TB and ART patients in primary care in Zambia.