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

描述(申请人提供)：反馈相关负波(FRN)是在头皮观察到的一种皮层反应，在反馈后约300ms表现为明显的负波，表明与获得相比，金钱损失。我们的工作表明，得失之间的神经分化是由腹侧纹状体产生的奖赏相关正电位驱动的，腹侧纹状体是基础神经节的一部分，参与了奖赏相关的神经回路。在一系列研究中，我们发现抑郁程度较高的人的FRN减少--最近在试点研究中将这项工作扩展到童年中期。这项工作与越来越多的数据相一致，这些数据表明，大脑腹侧纹状体的奖赏相关大脑活动减弱。在目前的提案中，我们将这项工作扩展到9岁儿童的大样本(N=300)，作为NIMH资助的大型研究的一部分，从3岁开始跟踪调查，以确定FRN是否与童年中期的抑郁症状有关(目标1)；根据我们的试点数据，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区别减少(即，FRN减少)有关。此外，我们想要检查FRN是否不仅与目前的抑郁症状有关，而且与样本中MDD风险的增加有关。为了解决这一可能性，本研究将研究FRN与两个与MDD发展相关的众所周知的危险因素：积极情绪的气质测量和MDD的家族史。我们预测，气质积极情绪性低的儿童(在6岁时评估)将表现为FRN减少(目标2)；此外，父母患有MDD的儿童将表现为FRN减少(目标3)。如果目标2和目标3得到证实，这些数据将表明FRN可能是MDD的危险标志物。这项研究的总体目标是评估与奖励相关的大脑活动与童年中期抑郁症状和MDD风险的关系。此外，本研究还将有助于关于个体气质和个性差异的发育神经生物学的文献。 公共卫生相关性：这项研究在300名9岁儿童的样本中探索了与奖励相关的大脑活动、抑郁症状和两个最著名的严重抑郁障碍发展的危险因素(即，MDD的父母病史和基于实验室的积极情绪测量)之间的关系。本研究旨在检验奖赏相关大脑活动的变化是否与这些众所周知的抑郁障碍发展风险因素有关；这项工作可能有助于识别风险的神经生物学标记物，并建立对奖赏的神经敏感性减弱作为从早期风险到后来抑郁发展的中间结果。

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.