Reward-related Brain Functioning as an Endophenotype for Depression

描述(由申请者提供)：拟议的这项指导性研究科学家发展奖(MRSDA)的目的是培训候选人在情感神经科学和青少年发展方面的相关知识，以了解积极情绪性(一种潜在的内在表型)在青少年抑郁症发展中的作用。了解内表型的作用对于识别那些抑郁症风险最大的人至关重要。虽然许多研究表明，积极的情绪性与抑郁和抑郁风险有关，但很少有人研究与奖励相关的大脑功能，以对抑郁的内表型进行关键测试。青春期是解决这一问题的一个特别重要的人生阶段，因为青春期是抑郁症的发病高峰期。应聘者擅长使用行为和自我报告方法评估积极情绪，抑郁父母的子女的童年早期发展，青年抑郁症，以及纵向数据分析。他寻求通过这个MRSDA以此专业知识为基础：(1)从专家导师和顾问那里学习有关功能磁共振成像(FMRI)方法的知识，以调查青少年大脑发育、与奖励相关的大脑功能和抑郁症的病理生理学；(2)完成情感神经科学、功能磁共振成像、数据分析和研究伦理方面的课程；(3)参加关于功能磁共振成像和神经成像数据分析的研讨会；以及(4)进行一项研究，探讨作为奖励相关大脑功能的积极情绪的关键测试，作为抑郁症的内部表型。匹兹堡大学在情感神经科学、青少年发展和青少年抑郁症领域拥有广泛的资源，因此是进行这种培训的绝佳环境。这位候选人的导师埃里卡·福布斯博士和詹妮弗·西尔克博士在抑郁症、青少年发育和青少年抑郁症的情感相关大脑功能方面拥有丰富的专业知识。拟议的培训将在一项纵向研究的背景下进行，研究：(1)父母有抑郁史(N=45)和没有抑郁史(N=30)的非抑郁青少年之间与奖赏相关的大脑功能的差异；(2)18个月期间与奖赏相关的大脑功能与抑郁症状之间的预期关系；以及(3)通过与奖赏相关的大脑功能和积极情绪的自我报告测量来预测抑郁症状的发展。这将为每种识别抑郁症风险的方法的比较效用提供证据。与国家精神卫生研究所概述的优先事项一致，拟议的MRSDA有可能通过调查行为和生物过程来解决风险机制。此外，培训和研究的结合将成为候选人独立研究生涯的跳板，进一步阐明积极情绪在青春期抑郁发展中的作用。

DESCRIPTION (provided by applicant): The aim of the proposed This Mentored Research Scientist Development Award (MRSDA) is to train the candidate in affective neuroscience and adolescent development relevant to understanding the role of positive emotionality, a potential endophenotype, in the development of depression in youth. Understanding the role of endophenotypes is critical for identifying those at greatest risk for depression. Although a number of studies demonstrate that positive emotionality is implicated in depression and risk for depression, few have examined reward-related brain function in the service of conducting critical tests of endophenotypes for depression. Adolescence is a particularly important point in the lifespan to address this issue because it is the peak time of onset for depression. The candidate has expertise in assessing positive emotionality using behavioral and self- report methods, early childhood development in offspring of depressed parents, youth depression, and longitudinal data analysis. He seeks to build on this expertise through this MRSDA to (1) learn from expert mentors and consultants about functional magnetic resonance imaging (fMRI) approaches to investigating adolescent brain development, reward-related brain function, and pathophysiology of depression; (2) complete coursework in affective neuroscience, fMRI, data analysis, and research ethics; (3) attend workshops on fMRI and neuroimaging data analysis; and (4) conduct a study examining critical tests of positive emotionality, operationalized as reward-related brain functioning, as an endophenotype for depression. The University of Pittsburgh is a phenomenal environment to pursue this training as it has extensive resources in the areas of affective neuroscience, adolescent development, and adolescent depression. The candidate's mentors, Drs. Erika Forbes and Jennifer Silk, have extensive expertise in affect-related brain functioning in depression, adolescent development, and adolescent depression. The proposed training will occur in the context of a longitudinal study examining: (1) differences in reward-related brain functioning between non-depressed adolescents of parents with (N = 45) and without (N = 30) a history of depression; (2) the prospective relationship between reward-related brain functioning and depressive symptoms over an eighteen month period; and (3) prediction of the development of depressive symptoms prospectively predicted by reward- related brain functioning and self-report measures of positive emotionality. This will provide evidence for the comparative utility of each approach of identifying those at risk for depression. Consistent with the priorities outlined by the National Institute of Mental Health, the proposed MRSDA has the potential to address mechanisms of risk through investigating behavioral and biological processes. Further, the combination of training and research will serve as a spring board for the candidate's independent research career to further elucidate the role of positive emotionality in the development of depression during adolescence.