Neurobehavioral Predictors of Emotional Deficits in Youth at Risk for Depression

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DESCRIPTION (provided by applicant): Depression rates dramatically increase during adolescence when offspring of depressed parents are 3-4 times more vulnerable compared to their peers. Adolescence is a sensitive period in the development of neural circuits supporting cognitive-affective processes involved in emotion processing and regulation. Research has implicated motivational and emotional deficits in depression. Emotions are based on a motivational system that guides an individual to adaptively and flexibly respond to features of the environment. However, little is known regarding the development of neural correlates involved in processing emotionally salient information that may be implicated in depression vulnerability or how these neural correlates relate to the development of depression symptoms over time. Further, it is largely unknown how these neural mechanisms correspond to real world behaviors, which is key to understanding their clinical significance and developing targeted treatments. The candidate proposes to examine neurobehavioral markers of emotional processing and regulation in a sample of 45 youth at high risk for depression (by virtue of having a parent with early onset depression) and 45 low risk peers. These youth and their families have already been followed extensively through Dr. Maria Kovacs' longitudinal childhood depression research studies from which extensive archival clinical data is available. In an innovative design, the candidate will examine neural indices of emotional processing using Event Related Potentials (ERPs), with a focus on the Late Positive Potential (LPP) and Feedback Negativity (FN). The candidate will integrate these neural indices with a 9-day Ecological Momentary Assessment (EMA) protocol of emotional reactions and regulation responses in daily life in order to identify brain-behavior relationships involved in emotional processing. Aim 1 will examine the extent to which high risk youth exhibit altered LPP and FN in response to emotional processing and regulation tasks. Aim 2 will examine the degree to which high and low risk youth differ on their emotional reactions and regulation responses in daily life. Aim 2 will also determine the brain-behavior relationships between neural and daily life indices of emotion. Aim 3 will examine the extent to which neural and daily life measures of emotion predict the longitudinal course of depressive symptoms over a 1-year follow-up. The candidate's long-term career goal is to become an independent investigator with expertise in the developmental affective neuroscience of depression. To address the research and training aims of this proposal, the candidate seeks to build upon her strong foundation in the experimental psychopathology of emotion through the following training aims: 1) gain conceptual expertise in developmental affective neuroscience; 2) achieve a deeper understanding of the clinical assessment of youth and developmental aspects of depression, including use of longitudinal high risk designs; 3) gain a deeper methodological expertise in collecting, processing, and analyzing ERP data of emotional processing in youth; and 4) achieve methodological expertise in collecting, processing, and analyzing EMA data measuring emotional responding and regulation in youth, including the conceptual and technical ability to integrate daily life measure with neural indices. The Department of Psychiatry at the University of Pittsburgh School of Medicine is an outstanding environment in which to engage in interdisciplinary training and integrative research necessary to achieve these research and training goals. The candidate's mentorship team (Drs. Ladcouer, Silk, and Kovacs) and consultant team (Drs. Hajcak Proudfit, Kuppens, and Wallace) have extensive experience in developmental affective neuroscience methods (including use of ERP methods), longitudinal high risk designs, use of EMA methods to examine emotion in daily life, conceptual and practical issues in measuring emotion regulation, and statistical expertise in multilevel and longitudinal analyses. The proposed study is the first to integrate neurobehavioral measures in a longitudinal design with youth at high risk for depression before they experience their first depressive episode. Findings will inform the design of larger R01 studies to examine bi-directional brain-behavior relationships, to elucidate specific developmental processes related to gender and social environment of high risk youth, and to identify specific targets for intervention and prevention of pediatric mood disorders. In conclusion, the proposed K01 application would provide the candidate with the training and research background to conduct independent research that integrates developmental and neurobehavioral affective neuroscience approaches to understand mechanisms underlying emotional dysfunction in youth vulnerable to developing depression.