Major Depressive Disorder: Longitudinal Analysis of Impact on Clinical and Behavioral Outcomes in Uganda.

BACKGROUND: There is still wide variability in HIV disease course and other HIV-related outcomes, attributable in part to psychosocial factors such as major depressive disorder (MDD), a subject that has received little attention in sub-Saharan Africa. METHODS: Using a longitudinal cohort of 1099 HIV-positive antiretroviral therapy-naive persons, we investigated the impact of MDD on 4 HIV-related negative outcome domains in Uganda. MDD was assessed using a Diagnostic Statistical Manual IV-based tool. Also collected were data on surrogate measures of the HIV-related outcome domains. Data were collected at the 3 time points of baseline, 6, and 12 months. Multiple regression and discrete time survival models were used to investigate the relationship between MDD and indices of the HIV outcomes. RESULTS: MDD was a significant predictor of "missed antiretroviral therapy doses" [adjusted odds ratio (aOR) = 4.75, 95% confidence interval (CI): 1.87 to 12.04, P = 0.001], "time to first visit to healthy facility" (aOR = 1.71; 95% CI: 1.07 to 2.73; P = 0.024), "time to first self-reported risky sexual activity" (aOR = 2.11, 95% CI: 1.27 to 3.49; P = 0.004) but not of "CD4 counts at months 6 and 12" (estimated effect 29.0; 95% CI: -7.8 to 65.7; P = 0.12), and "time to new WHO stage 3 or 4 clinical event" (aOR = 0.52, 95% CI: 0.12 to 2.20, P = 0.37). CONCLUSIONS: MDD significantly impacted 3 of the 4 investigated outcome domains. These results by demonstrating the adverse consequences of an untreated mental health disorder (MDD) on HIV-related outcomes further strengthen the need to urgently act on WHO's call to integrate mental health care in general HIV care.

Association between major depressive disorder and pro-inflammatory cytokines and acute phase proteins among HIV-1 positive patients in Uganda.

BACKGROUND: Major depressive disorder (MDD) is a common psychiatric complication of HIV/AIDS. While considerable research has been undertaken to understand the psychosocial risk factors of MDD, there is a paucity of data on its biological risk factors including immunological factors. To address this we undertook a study to investigate the association between MDD and pro-inflammatory cytokines and acute phase proteins among persons living with HIV/AIDS (PLWHA) in Uganda. We collected clinical and laboratory data on 201 PLWHA attending two HIV clinics in central and southwestern Uganda. Clinical data included DSM-IV based MDD diagnosis, while laboratory data included the concentrations of IL-6, TNF-α and CRP measured using ELISA. Multiple logistic linear regression analysis was used to determine which proteins were independently significantly associated with MDD controlling for study site, sex, age and highest educational attainment. RESULTS: The prevalence of MDD was 62/201 (30.8%). Adjusting for confounders, the odds of MDD increased with increasing levels of IL-6 [each unit increase in IL-6 titres was associated with an aOR = 0.98 (95% CI, 0.97-0.99); p < 0.001]. Participants with low levels of TNF-α were at reduced risk of MDD compared to participants with no TNF-α [those with a TNF-α of 1- <50 pg/ml titres had an aOR = 0.35(95% CI,0.10-1.16)], but as the level of TNF-α increased, the risk of MDD increased, and in particular participants with high levels of TNF-α (of 500 or above) were at a significantly increased risk of MDD [e.g. those with a TNF-α of 500- < 1000 pg/ml titres had an aOR = 3.98 (95% CI,1.29-12.33)] compared to participants with no TNF-α. There was no evidence that MDD was associated with the level of CRP titres [aOR = 0.95 (0.78-1.15); p = 0.60)]. CONCLUSION: In this study, the pro-inflammatory proteins IL-6 and TNF-α were significantly associated with MDD, while CRP was not.

Association between serotonin transporter gene polymorphisms and increased suicidal risk among HIV positive patients in Uganda.

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.

Major depressive disorder and suicidality in early HIV infection and its association with risk factors and negative outcomes as seen in semi-urban and rural Uganda.

INTRODUCTION: There is a paucity of research into the psychiatric problems associated with early stage HIV clinical disease in sub-Saharan Africa. METHODS: A cross sectional study was undertaken among 899 adult ART naïve persons in early stage HIV clinical disease (participants with CD4≥250 and who were at WHO clinical Stage I or II) attending a semi-urban and a rural clinic in Uganda. RESULTS: The prevalence of major depressive disorder in this study was 14.0% [95% CI 11.7-6.3%] while that of 'moderate to high risk for suicidality' was 2.8% [95% CI 1.7%; 3.9%]. Multivariable analyses found that factors in the socio-demographic, vulnerability/protective and stress (only for major depressive disorder) domains were significantly associated with both major depressive disorder and 'moderate to high risk for suicidality'. Major depressive disorder but not 'moderate to high risk for suicidality' was significantly associated with impaired psychosocial functioning, greater utilisation of health services and non-adherence to septrin/dasone. Neither major depressive disorder nor 'moderate to high risk for suicidality' was associated with CD4 counts, risky sexual behaviour nor with non-utilisation of condoms. LIMITATIONS: The bidirectional nature of some of the relationships between the investigated psychiatric problems, risk factors and outcomes in this cross sectional study makes it difficult to elucidate the actual direction of causality. CONCLUSION: Early stage HIV clinical disease is associated with considerable major depressive disorder and 'moderate to high risk for suicidality'. Therefore there is a need to integrate mental health into HIV interventions that target early stage HIV disease.

Incidence and Persistence of Major Depressive Disorder Among People Living with HIV in Uganda.

Data on the course of major depressive disorder (MDD) among people living with HIV (PLWH) are needed to inform refinement of screening and interventions for MDD. This paper describes the incidence and persistence rate of MDD in PLWH in Uganda. 1099 ART-naïve PLWH attending HIV clinics in Uganda were followed up for 12 months. MDD was assessed using the DSM IV based Mini-International Neuropsychiatric Interview with a prevalence for MDD at baseline of 14.0 % (95 % CI 11.7-16.3 %) reported. Multivariable logistic regression was used to determine predictors of incident and persistent MDD. Cumulative incidence of MDD was 6.1 per 100 person-years (95 % CI 4.6-7.8) with significant independent predictors of study site, higher baseline depression scores and increased stress. Persistence of MDD was 24.6 % (95 % CI 17.9-32.5 %) with independent significant predictors of study site, higher baseline depression scores, and increased weight. Risks of incident and persistent MDD observed in this study were high. Potentially modifiable factors of elevated baseline depressive scores and stress (only for incident MDD) were important predictors of incident and persistent MDD.