Developing rumination-focused treatment to reduce risk for depression recurrence (RDR) in adolescence

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Emerging evidence suggests that the recurrent form of Major Depressive Disorder (MDD) tends to worsen, with more severe and longer episodes as people move into adulthood. Yet, we are still a very long way from treatments that can reduce short- and long-term Risk for Depressive Relapse (RDR). Understanding specific mechanisms of RDR is urgently needed to promote relapse prevention (and may have long-term benefits for treatment). The present proposal uses a treatment that has evidence for modifying the ruminative habit, a tendency to approach difficulties and associated negative emotions with a repetitive, passive and abstract mental pattern (habit). In contrast, we teach adolescents to utilize adaptive, concrete and specific mental patterns (e.g., problem-solving, emotion processing). Rumination focused CBT (RFCBT) was developed to specifically target and reduce or modify the ruminative habit. Initial work among adults and our pilot data among adolescents suggests that rumination can be effectively reduced with RFCBT. In addition, work by our group and a few other small studies suggests that the ruminative habit can be measured at the neural level in connectivity of brain nodes in the Default Mode Network (DMN, increased within network connectivity) as well as in patterns of connectivity between the DMN and Cognitive Control Network (CCN). As such, we proposed to use RFBCT to modify the ruminative habit in 160 adolescents (age 14-18) with remitted MDD (via KSAD-PL) and elevated rumination (above T of 50), with the goal of achieving significant clinical change in rumination, and to observe changes in connectivity between key DMN and CCN nodes associated with decline in the ruminative habit. The latter knowledge may provide information on how to use alternative therapies (e.g., neuromodulation) to effectively modify the ruminative habit and the associated neural network pathways, which would lead to greater precision in the targeting of treatment. The RFCBT arm (N=30) is compared to an assessment only (AO) arm (N=30) for the R61, and to an active therapy, Relaxation Therapy (RelaxT) for the R33 (N = 50 in each group), that shares some of the active strategies for change.. For R61, we expect that (Aim 1) RF-CBT will result in (a) significant decreases in rumination and (b) decreased connectivity from LPPC to RIFG, both "Go" criteria for continuation to the R33 phase. For (Aim 2), we expect that degree of homework engagement will relate to degree of change in (a) ruminative habit, (b) in LPCC-RIFG rs-fMRI connectivity, and degree of increased activation during exploratory rumination induction task. Stability of RRS changes will also be evaluated at 12 months. This R61/R33 has the same Go criteria of RRS change (effect size of .5) and LPCC - RIFG connectivity changes (.5 effect size). In addition, the R33 adds prediction of MDD recurrence (Aims 3a (dimensional) and Aim 3b(categorical)) to proceed to the RO1 multisite phase. Our preliminary data suggest that even if our Go criteria are not met, we will make iterative gains in gaining a better understanding neural network targets, both in maintenance of or compensation for the ruminative habit, as well as for RDR.