Reward-Related Brain Activity: Biomarker for Risk of Depression in Childhood

描述（由申请人提供）：反馈相关负波（FRN）是在头皮处观察到的一种皮层电反应，作为反馈后约300 ms的表观负波，表明与收益相比的金钱损失。我们的工作表明，获得和损失之间的神经分化是由奖励相关的正电位驱动的，该正电位产生于腹侧纹状体-基底神经节的一部分，该部分与奖励相关的神经回路有关。在一系列的研究中，我们发现，FRN在更抑郁的个体中减少，最近在试点研究中将这项工作扩展到了童年中期。这项工作与越来越多的数据相一致，这些数据表明腹侧纹状体中与奖励相关的大脑活动减弱。在目前的建议中，我们将这项工作扩展到一个大样本（N=300）的9岁儿童，他们从3岁起就作为NIMH资助的大型研究的一部分进行了跟踪，以确定FRN是否与童年中期的抑郁症状有关（目标1）;根据我们的试验数据，我们假设童年中期抑郁症状的增加将与奖励和非奖励之间的差异减少有关（即，降低的FRN）。此外，我们想检查FRN是否不仅与当前的抑郁症状有关，而且与样本中MDD的风险增加有关。为了解决这种可能性，本研究将检查FRN与MDD发展相关的两个众所周知的风险因素：积极情绪性和MDD家族史的气质测量。我们预测，气质积极情绪性低的儿童（在6岁时评估）将以FRN降低为特征（目标2）;此外，父母患有MDD的儿童将以FRN降低为特征（目标3）。如果目标2和3得到确认，这些数据表明FRN可能是MDD的风险标志物。本研究的总体目标是评估奖励相关的大脑活动与抑郁症状之间的关系，以及儿童中期MDD的风险。此外，本研究将有助于文献的发展神经生物学的个性和气质的个体差异。 公共卫生相关性：这项研究探讨了奖励相关的大脑活动，抑郁症状和两个最著名的风险因素之间的关系，为后来的发展严重抑郁症（即，父母的抑郁症病史和实验室为基础的积极情绪的措施）在一个样本的300名9奥尔兹。本研究旨在检查奖励相关脑活动的变化是否与这些众所周知的抑郁症风险因素有关;这项工作可以帮助识别风险的神经生物学标志物，并建立对奖励的神经敏感性降低作为从早期风险到后期抑郁症发展的中间结果。

DESCRIPTION (provided by applicant): The feedback-related negativity (FRN) is an electrocortical response observed at the scalp as an apparent negativity approximately 300 ms following feedback indicating monetary loss compared to gain. Our work suggests that the neural differentiation between gains and losses is being driven by a reward-related positive potential that is generated in the ventral striatum-part of the basal ganglia that has been implicated in reward- related neural circuits. In a series of studies, we have found that the FRN is reduced in individuals who are more depressed-and have recently extended this work to middle childhood in pilot studies. This work is consistent with a growing body of data that indicates is characterized by attenuated reward-related brain activity in the ventral striatum. In the current proposal, we extend this work to a large (N=300) sample of 9 year-olds who have been followed as part of a large NIMH-funded study since age 3, to determine whether the FRN is related to depressive symptoms in middle childhood (Aim 1); based on our pilot data, we hypothesize that increasing depressive symptoms in middle childhood will be associated with reduced differentiation between rewards and non-rewards (i.e., a reduced FRN). Moreover, we want to examine whether the FRN is related not only the current depressive symptoms, but to increased risk for MDD in the sample. To address this possibility, the present study will examine the FRN in relation to two well-known risk factors related to the development of MDD: temperamental measures of positive emotionality and familial history of MDD. We predict that children low in temperamental positive emotionality (assessed at age 6) will be characterized by a reduced FRN (Aim 2); further, that children who have a parent who have had MDD will be characterized by a reduced FRN (Aim 3). If Aim 2 and 3 are confirmed, these data would suggest that the FRN may be a risk marker for MDD. The overall goal of this study is to evaluate the relationship between reward-related brain activity and depressive symptoms and risk for MDD in middle childhood. Additionally, the present study will contribute to the literature on the developmental neurobiology of individual differences in temperament and personality. PUBLIC HEALTH RELEVANCE: This study explores the relationship between reward-related brain activity, depressive symptoms, and two of the best-known risk factors for the later development of major depressive disorder (i.e., parental history of MDD and laboratory-based measures of positive emotionality) in a sample of 300 9-year olds. The present study aims to examine whether variation in reward- related brain activity relates to these well-known risk factors for developing depressive disorders; this work could help identify neurobiological markers of risk, and establish diminished neural sensitivity to rewards as an intermediate outcome on the pathway from early risk to the later development of depression.