Sensitive Periods, Brain Development and Depression

描述（由申请人提供）：暴露于早期虐待是抑郁症发展的主要风险因素。在过去的几年里，我们和其他人已经表明，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有自己的神经发育敏感期，当它们最容易受到早期压力的影响时，并发表了支持这些假设的第一个初步研究结果。特别是，我们发现，海马，胼胝体和额叶皮层是最脆弱的3-5，9=10和14-16岁，分别。此外，我们假设，精神病后遗症的虐待将取决于，至少部分地，在有关区域敏感期的压力源的时间。 这项研究计划的目的是确定这些区域神经发育敏感期的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，即存在离散的敏感期，在这些敏感期内，暴露于虐待或损失与抑郁症的风险最大程度地相关。此外，我们将检验抑郁症发展的敏感期与左海马和部分前额叶皮层的脆弱窗口重叠的假设，并确定其他大脑区域是否有与抑郁症敏感期重叠的脆弱窗口。 接下来，我们将检验遗传因素增加抑郁症风险的假设，部分原因是放大和延长了抑郁症的敏感期。最后，我们将测试的假设，早期暴露于可容忍的压力源将有助于防止未暴露的儿童主机从发展抑郁症，如果他们随后暴露在敏感期。此外，促进神经发生、促进强烈的自尊感或提供支持性社会网络的经历将有助于预防暴露宿主出现抑郁症。 这些假设将在从社区招募的600人（20-25岁，约50%男性）样本中进行测试。将使用修改后的不良童年经历评分对每个童年阶段遭受虐待和损失的发育程度和时间进行回顾性量化。将通过容积T1和T2扫描和扩散张量图像对其中200例受试者的神经发育敏感期进行评价。 这些信息将大大提高我们对重性抑郁症的起源和病因的理解，并可能提供必要的关键见解，以设计预防或先发制人的抑郁症的发展方案。

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.