Neural Correlates of Stress and Perceived Control in Adolescent Depression

项目总结/摘要 感知缺乏控制，特别是在压力下，作为一个核心机制， 潜在的重度抑郁症（MDD），特别是在快感缺失症状升高的情况下。这 这种机制与青春期出现的抑郁症状特别相关， 对于女性青少年来说，与女性青少年相比， 他们的男性同伴然而，MDD中感知控制中断的神经基础仍然很差 明白越来越多的证据表明，感知控制与压力共享一个共同的神经回路 以及根植于腹侧纹状体（VS）和腹内侧前额叶皮层（vmPFC）的MDD。神经影像 研究一致地将减少的VS激活与MDD中的享乐能力缺陷联系起来。而且安 在压力下不能募集vmPFC被认为是MDD中适应不良的压力反应的基础。 与拟议的研究直接相关的是，感知到的缺乏控制也与减少 在健康成人中激活相同的VS-vmPFC电路。然而，迄今为止的研究还没有检查 MDD中感知控制的神经机制，以及压力如何调节感知控制相关的神经机制。 神经回路此外，知觉控制的神经成像尚未扩展到青少年 人口。目前的K23提案旨在填补这些关键的知识空白。因此，女性 患有和不患有MDD的青少年（年龄：14-18）将经历压力诱导， 磁共振成像（fMRI）。一个新的功能磁共振成像任务，旨在操纵控制的看法， 在应激诱导之前和之后施用。为了评估“现实生活”压力的神经预测因素， 反应和快感缺失症状，生态瞬时评估（EMA）协议将 在扫描后两周以及三个月和六个月的随访中进行。我们假设- 在MDD青少年中，与感知控制相关的vmPFC激活/连接将减弱 与健康的青少年相比。我们还预计，相对于健康的青少年， 将显示从之前到之后与感知控制相关的VS-vmPFC激活/连接减少 应力使用不同的分析单位，这项研究将提供一个丰富的理解与压力有关的 机制在青少年MDD，并将是第一个利用感知控制相关的神经机制， 预测未来的MDD症状。利用来自导师互补团队的专业知识（Diego博士 Pizzagalli & Erika福布斯）和顾问（Mauricio Delgado博士、Blaise Frederick博士、Kate Harkness博士和 加勒特菲茨莫里斯），申请人将接受青少年MDD功能神经解剖学培训（目标1）， 基于任务的功能磁共振成像（目标#2），压力神经生物学和压力评估（目标#3），以及EMA（目标#4）。的 拟议的培训计划将启动申请人进入一个独立的研究生涯，重点是压力相关的 青少年MDD的潜在机制。

Project Summary/Abstract Perceived lack of control, especially during stress, has garnered substantial interest as a core mechanism underlying major depressive disorder (MDD), particularly in the context of elevated anhedonic symptoms. This mechanism is especially relevant for depressive symptoms that develop during adolescence, and particularly for female adolescents, who show heightened susceptibility to disruptions in their sense of control compared to their male peers. Yet, the neural underpinnings of perceived control disruptions in MDD remain poorly understood. Mounting evidence indicates that perceived control shares a common neural circuitry with stress and MDD that is rooted in the ventral striatum (VS) and ventromedial prefrontal cortex (vmPFC). Neuroimaging studies have consistently linked reduced VS activation to hedonic capacity deficits in MDD. Moreover, an inability to recruit the vmPFC under stress has been posited to underlie maladaptive stress responses in MDD. Directly relevant to the proposed research, perceived lack of control has also been associated with reduced activation of this same VS-vmPFC circuit in healthy adults. However, studies to date have yet to examine neural mechanisms of perceived control in MDD, and how stress may modulate perceived control-related neural circuits. Additionally, neuroimaging of perceived control has not yet been extended to adolescent populations. The current K23 proposal was designed to fill these critical knowledge gaps. Accordingly, female adolescents (age: 14-18) with and without MDD will undergo a stress induction in conjunction with functional magnetic resonance imaging (fMRI). A novel fMRI task designed to manipulate perceptions of control will be administered before and after the stress induction. In order to assess neural predictors of “real-life” stress responses and anhedonic symptoms, an ecological momentary assessment (EMA) protocol will be administered in the two weeks after the scan and at three- and six-month follow-ups. We hypothesize that VS- vmPFC activation/connectivity in relation to perceived control will be blunted in adolescents with MDD compared to healthy adolescents. We also expect that relative to healthy adolescents, adolescents with MDD will show decreases in VS-vmPFC activation/connectivity associated with perceived control from before to after stress. Using different units of analysis, this study will provide a rich understanding of stress-linked mechanisms in adolescent MDD and will be the first to utilize perceived control-related neural mechanisms to predict future MDD symptoms. Drawing on the expertise from a complementary team of mentors (Drs. Diego Pizzagalli & Erika Forbes) and consultants (Drs. Mauricio Delgado, Blaise Frederick, Kate Harkness and Garrett Fitzmaurice), the applicant will receive training in adolescent MDD functional neuroanatomy (Goal #1), task-based fMRI (Goal #2), stress neurobiology and stress assessment (Goal #3), and EMA (Goal #4). The proposed training plan will launch the applicant into an independent research career focusing on stress-related mechanisms underlying adolescent MDD.