Evaluating the Relationship Between Depression and Cognitive Function Among Children and Adolescents with HIV in Zambia

Abstract

Depression is common among people living with HIV. Multiple studies demonstrate a link between depression and cognitive dysfunction in adults with HIV, but the association has been minimally investigated in children and adolescents with HIV in Africa. We conducted a cross-sectional analysis as part of the HIV-associated Neurocognitive Disorders in Zambia study, a prospective cohort study in Lusaka, Zambia. We included 208 perinatally-infected children with HIV ages 8-17 taking antiretroviral therapy and 208 HIV-exposed uninfected (HEU) controls. Cognition was assessed with a comprehensive neuropsychological battery. Depressive symptoms were evaluated using self-report and parent-report versions of the NIH Toolbox Sadness module and the Patient Health Questionnaire-9 (PHQ-9). Risk factors for depression and associations between depressive symptoms and cognition were evaluated in bivariable and multivariable regression models. Participants with HIV demonstrated higher levels of depressive symptoms than controls (mean NIH Toolbox Sadness T-Score 50 vs. 44, p < 0.01; mean PHQ-9 score 2.0 vs. 1.5, p = 0.03), and were more likely to have cognitive impairment (30% vs. 13%, p < 0.001). Risk factors for depressed mood included self-reported poor health (OR 7.8, p < 0.001) and negative life events (OR 1.3, p = 0.004) Depressed mood was associated with cognitive impairment in participants with HIV (OR = 2.9, 95% CI 1.2-7.2, p = 0.02) but not in HEU participants (OR 1.7, 95% CI 0.18-15.7, p = 0.6). In conclusion, depressed mood is common among youth with HIV in Zambia, and is associated with cognitive impairment. Depression may be a result of HIV-related stress and stigma, or may be part of the spectrum of HIV-associated neurocognitive disorders. The causal relationship between depressed mood and cognitive impairment is unclear and should be evaluated in future longitudinal studies.

Keywords: Depression; HIV; HIV-associated neurocognitive disorders; Pediatric neurology; Zambia.

Figure 1:

Depressive symptoms by HIV status as measured by the NIH Toolbox Sadness Module Self-report and Parent Report and the Patient Health Questionnaire 9 (PHQ-9). Depressive symptoms were significantly higher on all instruments utilized except for the Parent Report Version of the PHQ-9.

Figure 2:

Scatter plot with superimposed median spline plot of depressive symptoms on the NIH Toolbox Sadness Self-report module vs. NPZ8 score, demonstrating stronger relationship between depressive symptoms and poor cognitive performance in participants with HIV vs. HEU controls.

Figure 3:

Cognitive domain scores by depression status, ordered by difference between depressed and non-depressed participants. Immediate recall, processing speed, attention, and motor speed were all significantly worse in participants with HIV compared to HEU controls.