Abstract
BackgroundAdolescent-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.MethodThis 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.DiscussionRFCBT 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 registrationClinicalTrials.gov Identifier: NCT03859297, registered 01 March 2019.
Highlights
Adolescent-onset depression often results in a chronic and recurrent course, and is associated with worse outcomes relative to adult-onset depression
rumination-focused cognitive behavioral therapy (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
RFCBT is a promising candidate intervention for the prevention of depressive relapse and recurrence in adolescents following prior depressive episode(s), and may improve longer term outcomes for this at-risk population. These findings indicate that RFCBT is able to modify rumination in adolescents, and shows potential as a targeted intervention to reduce risk of depressive relapse in high-risk adolescents
Summary
Adolescent-onset depression often follows a chronic, recurrent course, and is associated with a number of long-term negative outcomes [14,15,16,17,18,19,20,21]. Understanding specific treatment mechanisms that can reduce shortand long-term risk for depressive relapse in young people who have experienced a depressive episode is important in order to improve clinical outcomes. RFCBT was developed to target maladaptive rumination, and has been found to be effective in reducing rumination and, subsequently,risk of depressive relapse in clinical trials with adults, and in a recent pilot trial with adolescents. The current study will use RFBCT in adolescents at risk of depressive relapse, with the goal of achieving both significant clinical change in rumination, and associated changes in connectivity between key DMN and CCN nodes that have been linked to decline in problematic rumination. Enhanced understanding of the neurocognitive mechanisms underpinning rumination and the prevention of depressive relapse could help to develop better targeted personalised intervention strategies
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