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: 7254700
• 负责人: CHRISTINE M HEIM
• 金额: $ 12.58万
• 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/7254700
• 关键词: Address; Adrenal Glands; Adverse event; Affect; Analysis of Variance; Animal Model; Battered Women; Behavioral; Biological; Biological Neural Networks; Brain; Brain Stem; Brain imaging; Cerebrovascular Circulation; Child Abuse; Childhood; Clinical; Clinical Research; Complement; Complex; Depressed mood; Depressive disorder; Depth; Development; Diagnosis; Discipline; Disease; Disease susceptibility; Emotional; Emotions; Endocrine; Epidemiologic Studies; Exhibits; Failure; Foundations; Functional Magnetic Resonance Imaging; Future; Genes; Genetic; Genetic Polymorphism; Genetic Risk; Genetic Status; Goals; HPSE gene; Hippocampus (Brain); Human; Human Genetics; Individual; Laboratories; Lesion; Life; Life Stress; Literature; Major Depressive Disorder; Measures; Mental Depression; Mental disorders; Mentored Research Scientist Development Award; Moods; Neurons; Neurosecretory Systems; Neurotic Disorders; Pathway interactions; Patients; Pattern; Personal Satisfaction; Persons; Pituitary Gland; Positron-Emission Tomography; Principal Investigator; Process; Recording of previous events; Recruitment Activity; Regulation; Relative (related person); Reporting; Research; Research Training; Risk; Risk Factors; Risk Marker; Stress; Stress Tests; System; Training; Translating; Woman; affective neuroscience; biological adaptation to stress; depressive symptoms; early experience; emotional trauma; hypothalamic-pituitary-adrenal axis; insight; multidisciplinary; neural circuit; neuroimaging; neuromechanism; neuronal circuitry; physical abuse; programs; psychobiology; psychosocial; relating to nervous system; research study; resilience; response; serotonin transporter; skills; social stress; trait

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）：该K01应用的目的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的临床心理生物学培训。培训计划包括正式的课程，教程和研究实践，这些课程将为研究压力与抑郁之间的关系以及在神经系统层面上的遗传适度提供必要的技能。多学科培训组件用于特定的实验。该研究计划直接建立在证据的基础上，表明早期生活压力（ELS）会增加成年后发展抑郁症的风险，这可能是通过引起对额外压力的敏感性的。来自抑郁症的神经影像学研究的结果表明，尽管从未研究过与ELS相关的风险和弹性，但反映了风险，疾病和补偿机制的结合，反映了皮质膜网络的可变功能变化。它是拟议项目的主要目标，旨在确定与抑郁疾病标志的抑郁症风险和韧性的神经标记。 60名妇女将分为3组，其中包括20个对照，20名不抑郁的妇女有童年的性/身体虐待史以及20名患有当前重度抑郁症（MOD）的妇女以及儿童期性/身体虐待的历史。两个直接针对抑郁途径的验证的充分的激活探针，并显示出对检测风险，韧性和疾病标志物的敏感性，即（a）（a）在悲伤情绪诱导过程中，脑血流的正电子发射层析成像（PET）以及（B）功能磁共振成像（FMRI）的自我磁性情感处理（FMRI）。方差分析将用于对比EL中的风险，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，并将评估与ELS-MDD组状态的相互作用。这项研究将增强我们对神经机制的理解，通过这些神经机制，ELS被转化为抑郁症，并将促进对ELS相互作用，遗传风险和神经内分泌状态在神经水平上的相互作用的见解。该K01奖将为候选人提供不同学科的深度和广度，这对于考虑将来对复杂精神病的多因素贡献者至关重要。