Neurobehavioral Predictors of Emotional Deficits in Youth at Risk for Depression

描述（由申请人提供）：抑郁症的发病率在青春期急剧上升，抑郁父母的后代比同龄人容易受到3-4倍的伤害。青春期是神经回路发育的敏感时期，神经回路支持参与情绪加工和调节的认知-情感过程。研究表明，抑郁症中存在动机和情感缺陷。情绪是建立在一种激励系统的基础上的，它引导个体对环境的特征做出适应性和灵活的反应。然而，关于处理情绪显著信息的神经相关物的发展，可能与抑郁易感性有关，或者这些神经相关物如何随着时间的推移与抑郁症状的发展有关，我们所知甚少。此外，这些神经机制如何与现实世界的行为相对应在很大程度上是未知的，这是理解其临床意义和开发靶向治疗的关键。候选人建议在45名抑郁症高风险青年（由于其父母患有早发性抑郁症）和45名低风险同龄人的样本中检查情绪处理和调节的神经行为标记。这些年轻人和他们的家庭已经通过Maria Kovacs博士的纵向儿童抑郁症研究进行了广泛的跟踪研究，从中可以获得大量的档案临床数据。在创新设计中，

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.