Trajectories of reward sensitivity and depression across adolescence

描述(申请人提供)：人们越来越关注发生在青春期的奖励敏感度的变化；特别是青春期，似乎是一个对奖励更敏感的时期。同时，青春期是抑郁症状显著增加的时期，而抑郁的特点是对奖励的敏感度降低。目前的项目将奖励敏感性作为一种潜在特征进行研究，综合运用了脑电、功能神经成像(FMRI)、行为和自我报告的测量方法。按照同样的思路，我们考虑对抑郁症状的多种评估(例如，父母和孩子的报告)，因此抑郁症状也可以被建模为潜在特征。目前的建议对9至14岁的大样本(N=300)女孩的奖赏敏感性和抑郁进行了检查；此外，这一样本将在初次就诊两年后进行检查，以便既可以检查横向关系也可以检查纵向关系。在我们的试点数据中，我们广泛关注反馈相关负性(FRN)，这是一种在头皮观察到的明显负性反应，在反馈后约300ms，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。我们发现，FRN与基于fMRI的纹状体对奖赏反应的测量以及奖赏敏感性的行为指标有关。此外，我们还发现，在抑郁程度较高的成年人和青少年中，FRN都会减少--最近我们发现，与奖励相关的大脑活动减少可以预测青少年抑郁症状在两年内的变化。目前的建议将这项工作扩展到一个更大的纵向样本，并纳入了奖励敏感度、抑郁症状和青春期的多种测量。我们将评估：a)在间隔2年的两个时间点的大样本中，奖励敏感度的多项测量与抑郁症状之间的关系(目标1)；b)奖励敏感度和抑郁症状的正常发育增加，特别是作为青春期阶段的函数(目标2)；c)奖励敏感度和抑郁症状之间的预期关系随着时间的推移，以及第一次评估的奖励敏感度是否可以预测两年后抑郁的变化(目标3)；最后，如果青春期的变化预示着奖励敏感度和后来的抑郁症状之间更紧密的联系(目标3)。还评估了一些次要目标(例如，对抑郁症状而不是焦虑症状的特异性；唾液睾酮作为青春期阶段标志的有效性；应激性生活事件的作用)。这个 本研究将对奖赏的发育神经生物学以及与青春期抑郁个体差异和抑郁风险相关的神经生物学变化的文献做出贡献。 公共卫生相关性：我们采用时序设计，在300名女性(9至14岁)中考察了青春期阶段和变化对奖励敏感性(RS；使用行为、事件相关电位、功能磁共振和自我报告方法测量)和抑郁症状的作用-并评估低RS是否可以预测抑郁。

DESCRIPTION (provided by applicant): There is increasing focus on changes in reward sensitivity that take place across adolescence; in particular, puberty appears to be a time characterized by increased sensitivity to rewards. At the same time, puberty is a time characterized by a significant increase in depressive symptoms, and depression is characterized by reductions in sensitivity to rewards. The current project examines reward sensitivity as a latent trait, capitalizing on a combination of EEG, functional neuroimaging (fMRI), behavioral, and self-report measures. Along the same lines, we consider multiple assessments of depressive symptoms (e.g., parent and child reports) so that depressive symptoms can also be modeled as a latent trait. The current proposal examines both reward sensitivity and depression in a large (N=300) sample of girls, ranging from 9 to 14 years of age; moreover, this sample will be examined two years after the initial visit, so that both cross-sectional and longitudinal relationships can be examined. In our pilot data, we have focused extensively on the feedback-related negativity (FRN), 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. We have found that the FRN relates to fMRI-based measures of striatal response to rewards, as well as behavioral metrics of reward sensitivity. Moreover, we have found that the FRN is reduced in both adults and adolescents who are more depressed-and have recently found that reduced reward-related brain activity can predict changes in depressive symptoms over the course of two years among adolescents. The current proposal extends this work into a much larger and longitudinal sample, and incorporates multiple measures of reward sensitivity, depressive symptoms, and puberty. We will assess: a) the relationship between multiple measures of reward sensitivity and depressive symptoms in a large sample that spans adolescence at two time points, separated by 2 years (Aim 1); b) normative developmental increases in both reward sensitivity and depressive symptoms, especially as a function of pubertal stage (Aim 2); c) prospective relations between reward sensitivity and depressive symptoms over time, and whether reward sensitivity at the first assessment can predict changes in depression two years later (Aim 3); finally, if pubertal changes predicts a stronger link between reward sensitivity and later depressive symptoms (Aim 3). A number of secondary aims are also evaluated (e.g., specificity to depressive symptoms and not anxious symptoms; utility of salivary testosterone as a marker of pubertal stage; role of stressful life events). The present study will contribute to the literature on the developmental neurobiology of reward, as well as the neurobiological changes related to individual differences in depression and risk for depression across adolescence. PUBLIC HEALTH RELEVANCE: We examine the role of pubertal stage and change on reward sensitivity (RS; measured using behavioral, ERP, fMRI, and self-report methods) and depressive symptoms among 300 females (aged 9 to 14) in a time-sequential design-and evaluate if low RS can predicts depression.