Mechanisms of rumination change in adolescent depression (RuMeChange): study protocol for a randomised controlled trial of rumination-focused cognitive behavioural therapy to reduce ruminative habit and risk of depressive relapse in high-ruminating adolescents

Abstract

Background Adolescent-onset depression often results in\xa0a 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.\xa0Randomized 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\xa0at the\xa0self-report, behavioral,\xa0and neural levels- using patterns of connectivity between the Default Mode Network (DMN) and Cognitive Control Network (CCN). Disrupted connectivity\xa0is\xa0a\xa0putative 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\xa0were correlated with change in rumination and depressive symptoms. Method This is a phase III two-arm,\xa0two-stage, RCT\xa0of 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\xa0Rumination 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\u2009weeks post-randomization. Secondary outcomes include change in symptoms of depression following treatment, recurrence of depression over 12\u2009months\xa0post-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\xa0in adolescents, and influence the identified\xa0self-report, behavioral, and neural mechanisms of\xa0change. Understanding\xa0mechanisms\xa0that underlie\xa0change in rumination is necessary to improve and further disseminate preventive interventions. Trial registration ClinicalTrials.gov Identifier: NCT03859297 , registered 01 March 2019.