在正常人群中发现潜在的抑郁症、焦虑症易患者是早期预防心理疾病的关键。近年来，对抑郁症脆弱者脑内变化的研究虽得到了更多的关注，但大多数研究是依据家族史或幼年精神创伤史等来定义抑郁症脆弱性的。事实上，不是所有的有家族史或幼年精神创伤史的都是抑郁症脆弱者，有些人也可成为抑郁症抵御者。依据大脑对刺激的动态变化来定义抑郁症脆弱性应该是一个更客观的测量指标。本项目将利用反复的精神压力诱发的脑内动态变化建立抑郁症脆弱性的新模型，同时研究与这一生物标记相关的心理因素与环境因素，并验证这一生物学标记的可信度。我们将采集血样本，为日后研究基因与环境对脑功能的影响打下基础。.因我们将依据脑内对压力刺激的动态反应变化来观察判断每个人的结果，这不仅可以检测潜在的抑郁症焦虑症易患者，又可避免因脑功能成像信号的个体差异大而难以用来做个体化诊断的弊病。该方法将为脑功能成像在个体化诊断的临床应用上提供一个新方向。

Identifying individuals who are potentially vulnerable to.depression is an important step toward prevention of depression. There is an.increasing interest in investigating underlying neural mechanisms of depression.vulnerability to identify biomarkers for vulnerable individuals. So far, family.history, risk genes, or early life stress (ELS) are typically used to define.depression vulnerability. However, it is well-known that some individuals with ELS.can develop resilience to depression. Therefore, using neural responses through.functional magnetic resonance imaging (fMRI) to directly identify depression.vulnerable individuals would be ideal and objective. However, because of large.individual differences in fMRI responses, one can hardly use fMRI responses for.individualized diagnosis. To compensate this weakness, we propose to observe neural.responses to a repeated stressor dynamically and use the changing trend in neural.activation within each subject to identify depression vulnerable individuals. In.response to a repeated stressor, such as meeting deadlines for multiple grant.submissions, some people habituate and neural responses in their emotional.processing system decrease quickly (habituated emotional response, HER). But.others may have prolonged emotional responses (PER) and even become sensitized to.the stressor such that brain responses get amplified over time. We hypothesize that.HER vs. PER in response to a repeated stressor differentiates those who are resilient.to depression from who are vulnerable to depression..Our pilot study revealed that decreased activation in an emotion regulatory.region, the ventromedial prefrontal cortex (vmPFC), and increased activation in an.emotion processing region, the amygdala, in later stressful trials relative to early.trials could be an index of PER; whereas continuously heightened activation in the.vmPFC but quickly dropped activation in the amygdala could be the feature of HER..In this proposed project, we will examine 200 nondepressed college students to.further investigate neural activation patterns (PER vs. HER) in response to a.repeated stressor and their underlying phenotypes. We will follow up all subjects.for two years to validate the PER and HER patterns. We will also examine differences.in neural circuits as a function of depression vulnerability or resilience as.measured by ELS and personality traits (rumination and mindfulness). Genotypes will.also be examined as an exploratory aim..The major innovative elements of this effort are: 1) setting up a new model.for detecting depression vulnerability at an individual level which even can be.considered as a new way for fMRI in clinical application; 2) translating personality.factors and exposure to early life stress into individual differences in depression.vulnerability and resilience.