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IntroductionThe phenotypic expression of mental health (MH) conditions among people with HIV (PWH) in Uganda and worldwide are heterogeneous. Accordingly, there has been a shift toward identifying MH phenotypes using data-driven methods capable of identifying novel insights into mechanisms of divergent MH phenotypes among PWH. We leverage the analytic strengths of machine learning combined with inferential methods to identify novel MH phenotypes among PWH and the underlying explanatory features.MethodsA total of 277 PWH (46% female, median age = 44; 93% virally suppressed [ 33). Clusters 2 (n = 32; anxiety phenotype) and 3 (n = 130; mixed anxiety/depression phenotype) reported minimal PTSD symptoms, with modest BAI (Cluster 2) and PHQ-9 (Cluster 3) elevations. Cluster 4 (n = 39; minimal symptom phenotype) reported no clinical MH symptom elevations. Comparisons revealed higher rates of sexual abuse during childhood among the PTSD phenotype vs. the minimal symptom phenotype (p = 0.03).DiscussionWe identified unique MH phenotypes among PWH and confirmed the importance of early life adversity as an early risk determinant for unfavorable MH among PWH in adulthood.

Abstract Background Adolescent-onset depression often results in a chronic and recurrent course, and is associated with worse outcomes relative to adult-onset depression. Targeting habitual depressive rumination, a specific known risk factor for relapse, may improve clinical outcomes for adolescents who have experienced a depressive episode. Randomized controlled trials (RCTs) thus far have demonstrated that rumination-focused cognitive behavioral therapy (RFCBT) reduces depressive symptoms and relapse rates in patients with residual depression and adolescents and young adults with elevated rumination. This was also observed in a pilot RCT of adolescents at risk for depressive relapse. Rumination can be measured at the self-report, behavioral, and neural levels- using patterns of connectivity between the Default Mode Network (DMN) and Cognitive Control Network (CCN). Disrupted connectivity is a putative important mechanism for understanding reduced rumination via RFCBT. A feasibility trial in adolescents found that reductions in connectivity between DMN and CCN regions following RFCBT were correlated with change in rumination and depressive symptoms. Method This is a phase III two-arm, two-stage, RCT of depression prevention. The trial tests whether RFCBT reduces identified risk factors for depressive relapse (rumination, patterns of neural connectivity, and depressive symptoms) in adolescents with partially or fully remitted depression and elevated rumination. In the first stage, RFCBT is compared to treatment as usual within the community. In the second stage, the comparator condition is relaxation therapy. Primary outcomes will be (a) reductions in depressive rumination, assessed using the Rumination Response Scale, and (b) reductions in resting state functional magnetic resonance imaging connectivity of DMN (posterior cingulate cortex) to CCN (inferior frontal gyrus), at 16 weeks post-randomization. Secondary outcomes include change in symptoms of depression following treatment, recurrence of depression over 12 months post-intervention period, and whether engagement with therapy homework (as a dose measure) is related to changes in the primary outcomes. Discussion RFCBT will be evaluated as a putative preventive therapy to reduce the risk of depressive relapse in adolescents, and influence the identified self-report, behavioral, and neural mechanisms of change. Understanding mechanisms that underlie change in rumination is necessary to improve and further disseminate preventive interventions. Trial registration ClinicalTrials.gov Identifier: NCT03859297 , registered 01 March 2019.