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.

Public Health Relevance

In this revised competing renewal application focusing on mood repair and autonomic nervous system (ANS) functioning, we continue to conceptualize depression as a condition of bio-behavioral inflexibility and apply this framework to youths with juvenile-onset depression, their never-depressed high-risk siblings, and emotionally well controls. Three partially overlapping studies will examine: a) the relations of mood repair history and physiological/behavioral performance in the lab, to mood repair and its context in daily life, b) the ability to switch attention from negative material as a putative mechanism that undergirds adaptive mood repair, and c) the long-term predictive values of maladaptive mood repair and indices of atypical ANS functioning as bona fide risk factors for first onset clinical depression. The public health significance of this project derives from the fact that it will yield knowledge that can improve efforts to detect, prevent, and treat early-onset depression.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH084938-07
Application #
9303459
Study Section
Biobehavioral Mechanisms of Emotion, Stress and Health Study Section (MESH)
Program Officer
Murphy, Eric Rousseau
Project Start
2009-07-01
Project End
2021-06-30
Budget Start
2017-07-01
Budget End
2018-06-30
Support Year
7
Fiscal Year
2017
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Psychiatry
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Rottenberg, Jonathan; Kovacs, Maria; Yaroslavsky, Ilya (2018) Non-response to sad mood induction: implications for emotion research. Cogn Emot 32:431-436
Panaite, Vanessa; Bylsma, Lauren M; Kovacs, Maria et al. (2018) Dysregulated behavioral responses to hedonic probes among youth with depression histories and their high-risk siblings. Emotion :
Daches, Shimrit; Kovacs, Maria; George, Charles J et al. (2017) Childhood adversity predicts reduced physiological flexibility during the processing of negative affect among adolescents with major depression histories. Int J Psychophysiol 121:22-28
Kovacs, Maria; Lopez-Duran, Nestor L; George, Charles et al. (2017) The Development of Mood Repair Response Repertories: I. Age-Related Changes Among 7- to 14-Year-Old Depressed and Control Children and Adolescents. J Clin Child Adolesc Psychol :1-10
Yaroslavsky, Ilya; Rottenberg, Jonathan; Bylsma, Lauren M et al. (2016) Parasympathetic nervous system activity predicts mood repair use and its effectiveness among adolescents with and without histories of major depression. J Abnorm Psychol 125:323-36
Kovacs, Maria; Bylsma, Lauren M; Yaroslavsky, Ilya et al. (2016) Positive Affectivity is Dampened in Youths with Histories of Major Depression and Their Never-Depressed Adolescent Siblings. Clin Psychol Sci 4:661-674
Bylsma, Lauren M; Yaroslavsky, Ilya; Rottenberg, Jonathan et al. (2016) Familiality of mood repair responses among youth with and without histories of depression. Cogn Emot 30:807-16
Kovacs, Maria; Yaroslavsky, Ilya; Rottenberg, Jonathan et al. (2015) Mood repair via attention refocusing or recall of positive autobiographical memories by adolescents with pediatric-onset major depression. J Child Psychol Psychiatry 56:1108-17
Rimay, Timea; Benak, Istvan; Kiss, Eniko et al. (2015) BDNF Val66Met polymorphism and stressful life events in melancholic childhood-onset depression. Psychiatr Genet 25:249-55
Nunley, Karen A; Ryan, Christopher M; Orchard, Trevor J et al. (2015) White matter hyperintensities in middle-aged adults with childhood-onset type 1 diabetes. Neurology 84:2062-9

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