Neural Correlates of Stress and Perceived Control in Adolescent Depression

青少年抑郁症中压力与感知控制的神经相关性

• 批准号: 10818855
• 负责人: Emily Belleau
• 金额: $ 5.4万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10818855
• 关键词: Adolescence; Adolescent; Adult; Anhedonia; Behavior; Behavioral; Biological Markers; Cells; Complex; Early Diagnosis; Ecological momentary assessment; Female Adolescents; Functional Magnetic Resonance Imaging; Functional disorder; Future; Goals; Knowledge; Life Stress; Link; Major Depressive Disorder; Mentors; National Institute of Mental Health; Neuroanatomy; Neurobiology; Perception; Population; Predisposition; Prefrontal Cortex; Protocols documentation; Research; Scanning; Stress; Symptoms; Training; Ventral Striatum; Work; biological adaptation to stress; career; child depression; comparison control; coping; depressive symptoms; design; hedonic; interest; male; neural; neural circuit; neural correlate; neuroimaging; neuromechanism; novel; peer; prospective; recruit; vulnerable adolescent

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, Christian Webb, 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.

项目摘要/摘要 被认为缺乏控制力，特别是在压力期间，已经引起了人们作为核心机制的极大兴趣 潜在的严重抑郁障碍(MDD)，特别是在非享乐症状升高的背景下。这 机制与青春期出现的抑郁症状特别相关，尤其是 对于女性青少年来说，她们在控制感方面表现出更高的受扰性 她们的男性同伴。然而，MDD患者感觉到的控制中断的神经基础仍然很差。 明白了。越来越多的证据表明，知觉控制与压力有着共同的神经回路。 起源于腹侧纹状体(VS)和腹内侧额叶皮质(VmPFC)的MDD。神经成像 研究一致地将MDD中的享乐能力缺陷与VS激活减少联系起来。此外，一个 不能在应激状态下招募vmPFC被认为是MDD不良适应应激反应的基础。 与拟议的研究直接相关的是，感觉到的缺乏控制力也与减少 在健康成年人中激活相同的vs-vmPFC电路。然而，到目前为止的研究还没有检查 MDD患者知觉控制的神经机制，以及压力如何调节知觉控制相关 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岁)将接受压力诱导和功能性 磁共振成像(FMRI)。一项旨在操纵控制知觉的新型fMRI任务将是 在应激诱导前后给药。为了评估“现实生活”压力的神经预测因子 响应和非享乐症状，生态瞬时评估(EMA)方案将是 在扫描后两周以及三个月和六个月的随访中进行治疗。我们假设VS- 患有MDD的青少年与感知控制相关的vmPFC激活/连接将变迟钝 与健康的青少年相比。我们还预计，相对于健康的青少年，患有MDD的青少年 将显示与感知控制相关的VS-vmPFC激活/连接性从之前到之后的下降 压力。使用不同的分析单位，这项研究将提供对压力相关的丰富理解 青少年MDD的机制，并将首次利用知觉控制相关的神经机制来 预测未来的MDD症状。利用来自互补的导师团队的专业知识(Diego博士 Pizzagalli&Erika Forbes)和顾问(毛里西奥·德尔加多博士、布莱斯·弗雷德里克博士、凯特·哈克尼斯博士、克里斯蒂安 Webb和Garrett Fitzmaurice)，申请者将接受青少年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)、应激神经生物学和压力评估(目标3)和EMA(目标 #4)。拟议的培训计划将使申请者进入专注于以下方面的独立研究生涯 青春期MDD背后的压力相关机制。

项目成果

Distinct stress-related medial prefrontal cortex activation in women with depression with and without childhood maltreatment.

• DOI: 10.1002/da.23243
• 发表时间: 2022-04
• 期刊: DEPRESSION AND ANXIETY
• 影响因子: 7.4
• 作者: Dong, Daifeng;Belleau, Emily L.;Ironside, Maria;Zhong, Xue;Sun, Xiaoqiang;Xiong, Ge;Cheng, Chang;Li, Chuting;Wang, Xiang;Yao, Shuqiao;Pizzagalli, Diego A.
• 通讯作者: Pizzagalli, Diego A.

Parsing Heterogeneity in Mood Disorders: The Challenges of Modeling Stable Mood Disorder-Related Functional Connectomes.

• DOI: 10.1016/j.bpsc.2021.10.009
• 发表时间: 2022-01
• 期刊: Biological psychiatry. Cognitive neuroscience and neuroimaging
• 作者: Belleau EL

Sex-specific neural responses to acute psychosocial stress in depression.

• DOI: 10.1038/s41398-021-01768-y
• 发表时间: 2022-01-10
• 期刊: Translational psychiatry
• 影响因子: 6.8
• 作者: Dong D;Ironside M;Belleau EL;Sun X;Cheng C;Xiong G;Nickerson LD;Wang X;Yao S;Pizzagalli DA
• 通讯作者: Pizzagalli DA