Malleability of rumination: An exploratory model of CBT-based plasticity and long-term reduced risk for depressive relapse among youth from a pilot randomized clinical trial.

Early-onset depression is associated with increased lifespan chronicity, suicidality, and the functional burdens associated with recurrent episodes. Reduction of these negative long-term outcomes requires an understanding of what interventions reduce vulnerabilities or ameliorate their associated neural patterns. Rumination-Focused Cognitive Behavior Therapy (RFCBT), an evidence-based treatment which directly targets a well-known risk for depressive relapse (i.e., ruminative habit), has shown preliminary success for reducing relapse rates among adolescents and adults in remission from Major Depressive Disorder (rMDD). In the current pilot study, clinical outcomes and neuroimaging predictors are explored over two years following a randomized controlled trial of eight weeks of RFCBT (n = 17) or Assessment Only (AO; n = 16) to prevent depressive relapse among adolescents. Baseline neural activation during a rumination induction task, neural change during treatment, and treatment group are examined as predictors of relapse. Regions selected were based upon hyperactivation patterns in rMDD compared to healthy adolescents, and occurred largely in default mode, somatomotor, visual and salience network regions. Twenty-five adolescents successfully completed quality fMRI scans at Baseline and after eight weeks of RFCBT or AO. RFCBT-treated youth maintained lower depression scores over the two-year period, relapsed at slower and less frequent rates, and were hospitalized less often for suicidality than AO. Although both groups reported lower ruminative tendencies after one year, at two-year follow-up, RFCBT maintained reductions whereas AO reported a return of ruminative tendencies. Adolescents who demonstrated higher activation at Baseline in default mode and limbic regions during rumination induction reported reduced depressive symptoms over the follow-up period. These data offer preliminary evidence that targeting rumination can stave off depressive relapse among vulnerable adolescents, and that such targeted treatment may aid a compensation process for disease-related brain functioning reducing risk to further depressive episodes. Clinical trials registration NCT01905267, https://clinicaltrials.gov/ct2/show/NCT01905267