Sensitive Periods, Brain Development and Depression

敏感期、大脑发育和抑郁

基本信息

批准号：
7980016
负责人：
MARTIN H TEICHER
金额：
$ 73.76万
依托单位：
MCLEAN HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-01 至 2015-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7980016
关键词：
16 year old Accounting Age-Years Aggressive behavior Alcoholism Brain Brain region Child Child Abuse Child Sexual Abuse Childhood Clinical Communities Corpus Callosum Depressive disorder Development Diffusion Magnetic Resonance Imaging Disease Dissociation Drug abuse Environment Etiology Event Exposure to Family history of Feeling Female Fostering Functional disorder Genes Genetic Genetic Polymorphism Goals Growth Hippocampus (Brain)Household Individual Inherited Left Magnetic Resonance Imaging Major Depressive Disorder Measures Mental Depression Mission Neurobiology Neurons Personality Disorders Phase Play Population Attributable Risks Post-Traumatic Stress Disorders Predisposition Prefrontal Cortex Prevention program Psychopathology Publishing Recruitment Activity Research Resistance Risk Risk Factors Role Sampling Scanning Shapes Social Network Staging Stress Structure Testing Time base design emotional abuse experience frontal lobe gray matter high risk insight interest male neurogenesis preempt prevent programs psychosocial public health relevance response self esteem stressor

项目摘要

DESCRIPTION (provided by applicant): Exposure to early abuse is a major risk factor for the development of depression. Over the last several years we, and others, have shown that childhood abuse is associated with alterations in brain structure. Recently, we hypothesized that different brain regions have their own individual neurodevelopmental sensitive periods when they are maximally susceptible to the effects of early stress, and have published the first preliminary findings that support these hypotheses. In particular, we found that the hippocampus, corpus callosum and frontal cortex were maximally vulnerable at 3-5, 9=10 and 14-16 years of age, respectively. In addition we hypothesized that the psychiatric sequela of abuse would depend, at least in part, on the timing of the stressor in relation to regional sensitive periods. The aims of this program of research is to ascertain if these preliminary findings of regional neurodevelopmental sensitive periods can be replicated, extended to males and to other forms of adversity besides childhood sexual abuse. Second, we will test our hypothesis that there are discrete sensitive periods when exposure to abuse or loss is maximally associated with risk for developing depression. Further, we will test the hypothesis that sensitive periods for the development of depression overlap with windows of vulnerability for left hippocampus and portions of prefrontal cortex, and will also ascertain if other brain regions have windows of vulnerability that overlap with the sensitive period for depression. Next we will test the hypothesis that hereditary factors increase risk for depression, in part, by amplifying and extending the sensitive period for depression. Finally, we will test the hypotheses that early exposure to tolerable stressors will help to inoculate unexposed child hosts from developing depression if they are subsequently exposed during the sensitive period. Further, experiences that foster neurogenesis, facilitate strong feelings of self-esteem or provide a supportive social network will help to preempt the emergence of depression in exposed hosts. These hypotheses will be tested in a sample of 600 individuals (20-25 years of age, ~50% male) recruited from the community. Degree and timing of developmental exposure to abuse and loss across each childhood stage will be quantified retrospectively using a modified Adverse Childhood Experience score. Neurodevelopmental sensitive periods will be evaluated in 200 of these subjects from volumetric T1 and T2 scans and diffusion tensor images. This information will greatly enhance our understanding of the genesis and etiology of major depression and may provide critical insights necessary to design programs to prevent or preempt the development of depressive disorders. PUBLIC HEALTH RELEVANCE: Exposure to early abuse alters trajectories of brain development and is a major risk factor for the development of depression. We will test the hypothesis that the psychiatric consequences of exposure to early abuse and loss depend on the timing of the stressor in relationship to neurodevelopmental sensitive periods, which are influenced in amplitude and timing by hereditary factors and modulated by protective factors.

描述（由申请人提供）：暴露于早期虐待是抑郁症发展的主要危险因素。在过去的几年中，我们和其他人表明，儿童虐待与大脑结构的改变有关。最近，我们假设不同的大脑区域具有自己的个体神经发育敏感时期，因为它们最大程度地容易受到早期压力的影响，并发表了支持这些假设的第一个初步发现。特别是，我们发现海马，call体和额叶皮层分别在3-5、9 = 10和14-16岁时最大化。此外，我们假设虐待的精神续集至少部分取决于与区域敏感时期有关的压力源的时间。该研究计划的目的是确定区域神经发育敏感时期的这些初步发现是否可以复制，扩展到男性和其他形式的逆境，除了儿童期性虐待。其次，我们将检验我们的假设，即在暴露于滥用或损失的情况下存在离散的敏感时期，与患抑郁症的风险最大相关。此外，我们将检验以下假设：抑郁症的发展敏感时期与左海马脆弱性和前额叶皮层的脆弱性重叠，并且还将确定其他大脑区域是否具有与抑郁症敏感时期重叠的脆弱性窗户。接下来，我们将检验以下假设：遗传因素部分通过扩大和延长抑郁症的敏感时期来增加抑郁症的风险。最后，我们将测试假设，即早期暴露于可忍受的压力源将有助于接种未暴露的儿童宿主，如果抑郁症随后在敏感时期暴露。此外，促进神经发生，促进自尊心或提供支持性社交网络的经验将有助于抢占暴露宿主中抑郁症的出现。这些假设将在从社区招募的600个人（20-25岁，约50％的男性）样本中进行检验。在每个童年阶段遭受虐待和损失的发展程度和时间，将使用修改后的不良儿童体验评分进行回顾性量化。神经发育敏感的周期将在这些受试者中的200个受试者中进行评估，从体积T1和T2扫描以及扩散张量图像。这些信息将大大增强我们对重度抑郁症的起源和病因的理解，并可能为设计计划所必需的关键见解提供预防或抢占抑郁症的发展。公共卫生相关性：暴露于早期虐待会改变大脑发展的轨迹，是抑郁症发展的主要危险因素。我们将检验以下假设：暴露于早期滥用和损失的精神科后果取决于压力源与神经发育敏感时期的关系的时间，这些时期受到遗传因素的振幅和时间影响，并受保护因素的调节。