Biobehavioral inflexibility and risk for juvenile-onset depression

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This REVISED competing renewal application builds on our recent study of the joint regulation of sad, dysphoric affect (mood repair) and cardiac indexes of autonomic nervous system (ANS) functioning (including respiratory sinus arrhythmia, RSA) among youths at varying levels of depression risk. In response to the IRG's comments, we provide information further on about the covariates we assess and sample characteristics; the effects of covariates on key outcomes; explicate further the study's significance; note changes in the Methods, and summarize new findings. Using a high-risk family design, we have been studying a clinical sample of adolescent probands with juvenile-onset depression (JOD) histories, their never- depressed (high-risk) siblings, and healthy controls. We propose 3 synergistic studies as the logical next step, based on our findings and the recent literature. Study 1 addresses the extent to which dysphoric mood in daily life reflects individual differences in features of mood repair responding and/or context, and how well contemporaneous lab-based assessment of mood repair and RSA relate to real-life mood repair. After a lab- protocol, affect and naturalistic mood repair will be sampled via Ecological Momentary Assessment in 100 probands, 100 high-risk siblings, and 100 controls; the 7-day sampling interval will overlap with each subject's birthday to assure a uniform life event with potential affective significance. Study 2 investigates mechanisms: it examines the hypothesis that the capacity to switch attention away from depressogenic material and associated dysphoria is a key mechanism of adaptive mood repair, subject to individual differences in biobehavioral functioning. Using a “proof of concept” approach, probands (n=160) will be randomly assigned to sham attention training or training to improve the ability to switch attention away from negative material; effects of attention training on mood repair will be examined in the context of RSA profiles and prior mood repair success. Study 3, which extends the follow-up period of the prior study, proposes that atypical RSA profiles (non-normative combinations of resting RSA+RSA response to sad mood) and low positive affectivity are bona fide, pre-morbid risk factors for first-onset depression: it will include 175 high-risk siblings and 175 healthy controls who did not yet have clinical depression at their last research evaluation. As a secondary goal, we will characterize developmental trajectories of mood repair repertoires from late childhood into emerging adulthood. Using multilevel modeling, study results will shed further light on when (and how) mood repair fails (or succeeds), attention as a mechanism, and the role of ANS functioning. Results also will serve to identify modifiable pre-morbid predictors of depression risk and developmental as well as contextual moderators of clinical outcomes. Overall therefore, the proposed study will contribute to evolving models of the etiology depression, and also help advance personalized therapeutic and preventive interventions for depression, with the ultimate goal of benefitting public health.