ArticleResearch square2026
Association of HIV infection and alcohol use on resting-state functional connectivity and mental health in youth living with perinatal HIV.
Article in Research square, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Background: Youth living with perinatally acquired HIV (YPHIV) are at increased risk for developing mental health disorders, particularly depression and anxiety, which may be compounded by alcohol use. Research in adults living with HIV indicates that both HIV infection and alcohol use have been linked to altered resting-state functional connectivity (RSFC) in limbic and striatal circuits, and that this, in turn, is associated with severity of anxiety and depressive symptoms. However, the combined effects of perinatal HIV infection, alcohol use and mental health on RSFC in YPHIV remain understudied. Methods: We conducted a cross-sectional analysis of 155 participants (73 HIV-negative controls (HC), 82 (YPHIV) from the Cape Town Adolescent Antiretroviral Cohort Substance, Imaging and Mental Health (CTAAC-SIM) study. All underwent 3T anatomical and resting-state functional MRI scanning, mental health assessments, urine dipstick for commonly used substances and self-reported substance use screening using the Alcohol, Smoking and Substance Involvement Screening Test (ASSIST). Seed-based connectivity (SBC) analyses focused on the medial prefrontal cortex and 16 bilateral subcortical seeds (four striatal nuclei, amygdala, hippocampus, thalamus and ventral tegmental area). We conducted an analysis of covariance and multivariate linear regression to assess RSFC differences between HC with/without reported alcohol use and YPHIV with/without reported alcohol use. In addition, we explored the association between RSFC and anxiety and depression symptom scores within the different groups. We controlled for age, gender and education. All results were FDR-corrected for multiple comparisons. Results: In YPHIV with alcohol use compared to YPHIV with no alcohol use, we found significantly greater RSFC of the right caudate to temporal, occipital and cerebellar regions. In YPHIV (with/without alcohol use) and HC (with/without alcohol use), altered RSFC of the thalamus and amygdala were associated with higher depression symptoms but not anxiety. Conclusion: Alcohol use in YPHIV may be associated with alterations in subcortical RSFC as well as depression severity. Our findings are consistent with previously reported RSFC changes in emotion- and reward-related circuitry in HIV.
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