Neural Substrates of Depression Risk after Child Abuse

虐待儿童后抑郁风险的神经基础

• 批准号: 7145582
• 负责人: CHRISTINE M HEIM
• 金额: $ 12.33万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7145582
• 关键词: behavioral /social science research tag; behavioral genetics; bioimaging /biomedical imaging; child abuse; clinical research; cortisol; developmental psychology; early experience; emotional adjustment; female; functional magnetic resonance imaging; genetic polymorphism; genetic susceptibility; human genetic material tag; human subject; interview; major depression; neuroendocrine system; neuroimaging; neuroregulation; positron emission tomography; serotonin transporter; statistics /biometry; stress

DESCRIPTION (provided by applicant): The goal of this K01 application is to complement the candidate's previous training in clinical psychobiology with specialized research training in functional brain imaging, affective neuroscience, and human genetics. The training plan includes formal coursework, tutorials and research practice that will provide foundation in skills necessary to study the relationship between stress and depression, as well as the genetic moderation of this relationship, at the neural systems level. The multidisciplinary training components are applied in a specific experiment. The research plan directly builds on evidence that early-life stress (ELS) increases risk for developing depressive disorders in adulthood, likely by inducing sensitization to additional stress. Findings from neuroimaging studies in depression suggest variable functional changes in cortical-limbic networks, reflecting a combination of risk, illness and compensatory mechanisms, though ELS-related risk and resilience have never been studied. It is the principal goal of the proposed project to identify neural markers of depression risk and resilience, relative to markers of depressive illness, in ELS. Sixty women will be recruited into 3 groups, including 20 controls, 20 never-depressed women with a history of childhood sexual/physical abuse, and 20 women with a diagnosis of current major depressive disorder (MOD) and a history of childhood sexual/physical abuse. Two well-validated activation probes that directly target depression pathways and have demonstrated sensitivity to detect risk, resilience and illness markers will be applied, i.e. (a) positron-emission tomography (PET) of cerebral blood flow during sad mood induction and (b) functional magnetic resonance imaging (fMRI) of self-referential emotional processing. Analysis of variance will be used to contrast neural markers of risk, resilience and MOD in ELS. The independent contributions of neuroendocrine stress response and genetic status (5HTTLPR polymorphism) to neural activation patterns will be studied and interactions with ELS-MDD group status will be evaluated. The study will enhance our understanding of the neural mechanisms, by which ELS is translated into depression and will promote insight into the interaction between ELS, genetic risk and neuroendocrine status at the neural level. This K01 award will provide the candidate with depth and breadth in distinct disciplines, which is critical for considering the multifactorial contributors to complex psychiatric disorders in the future.

描述（由申请人提供）：本 K01 申请的目标是通过功能性脑成像、情感神经科学和人类遗传学方面的专门研究培训来补充候选人之前在临床心理生物学方面的培训。培训计划包括正式课程、教程和研究实践，这些将为研究压力和抑郁之间的关系以及在神经系统层面上对这种关系的遗传调节提供必要的技能基础。多学科培训组件应用于特定实验。该研究计划直接建立在以下证据之上：早期生活压力（ELS）可能通过诱导对额外压力的敏感性增加成年后患抑郁症的风险。抑郁症的神经影像学研究结果表明，皮质边缘网络存在可变的功能变化，反映了风险、疾病和补偿机制的综合作用，尽管 ELS 相关的风险和恢复力从未被研究过。该项目的主要目标是在 ELS 中识别抑郁风险和恢复力的神经标记（相对于抑郁疾病的标记）。 60 名女性将被分为 3 组，其中包括 20 名对照组、20 名有童年性/身体虐待史的从未抑郁过的女性，以及 20 名被诊断患有当前重度抑郁症 (MOD) 且有童年性/身体虐待史的女性。将应用两种经过充分验证的激活探针，它们直接针对抑郁途径，并已证明对检测风险、恢复力和疾病标记物具有敏感性，即（a）悲伤情绪诱导期间脑血流的正电子发射断层扫描（PET）和（b）自我参照情绪处理的功能磁共振成像（fMRI）。方差分析将用于对比 ELS 中风险、弹性和 MOD 的神经标记。将研究神经内分泌应激反应和遗传状态（5HTTLPR 多态性）对神经激活模式的独立贡献，并评估与 ELS-MDD 群体状态的相互作用。该研究将增强我们对 ELS 转化为抑郁症的神经机制的理解，并将促进对 ELS、遗传风险和神经内分泌状态之间在神经水平上的相互作用的深入了解。 K01 奖项将为候选人提供不同学科的深度和广度，这对于考虑未来复杂精神疾病的多因素影响至关重要。