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

描述（由申请人提供）：反馈相关的负性（FRN）是在头皮观察到的一种皮层电反应，在反馈后大约300毫秒出现明显的负性，表明金钱损失与收益相比。我们的研究表明，获得和损失之间的神经分化是由与奖励相关的正电位驱动的，该电位产生于基底神经节的腹侧纹状体，与奖励相关的神经回路有关。在一系列的研究中，我们发现，在抑郁程度较高的个体中，FRN会减少。最近，我们在试点研究中将这项工作扩展到了儿童中期。这项工作与越来越多的数据一致，表明腹部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9岁儿童的大样本（N=300），这些儿童从3岁开始作为nimh资助的一项大型研究的一部分被跟踪，以确定FRN是否与儿童中期的抑郁症状有关（目的1）；根据我们的试点数据，我们假设儿童中期抑郁症状的增加将与奖励和非奖励之间的差异减少（即FRN减少）有关。此外，我们想要检查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。为了解决这一可能性，本研究将研究FRN与两个众所周知的与重度抑郁症发展相关的风险因素的关系：积极情绪的气质测量和重度抑郁症的家族史。我们预测，气质积极情绪低的儿童（在6岁时评估）将以FRN降低为特征（目的2）；此外，父母一方患有重度抑郁症的孩子将以FRN减少为特征（Aim 3）。如果目的2和目的3得到证实，这些数据将表明FRN可能是重度抑郁症的风险标志。本研究的总体目标是评估儿童中期奖励相关脑活动与抑郁症状和MDD风险之间的关系。此外，本研究将有助于在气质和个性的个体差异的发育神经生物学的文献。

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.