DEVELOPMENTAL MECHANISMS UNDERLYING THE RISK TO DEVELOP ANXIETY AND DEPRESSION

焦虑、抑郁和药物滥用是最常见的精神病理学类型 他们在青春期发病。在童年时期发现的焦虑气质是一个重要的风险因素 为以后这些疾病的发展做准备。由于机械和受控应力暴露实验 不能在儿童身上进行，拟议的研究将使用经过广泛验证的非人类灵长类动物 用最先进的功能成像和分子方法建立模型，了解神经回路和 青春期易患应激性精神病的分子机制。 这些研究的一个重要组成部分是，他们将在年轻的非人类灵长类动物身上使用 类似于人体研究中的评估，包括功能和结构成像，以 前瞻研究儿童杏仁核反应性增强与脑血管紧张素转换酶损伤的关系 青春期应激诱发的精神病理学。重要的是，脑组织将被收集来评估 青少年杏仁核促肾上腺皮质激素释放因子系统失调的程度 易患焦虑症和抑郁症。预计这些研究将发现：1)增加 儿童时期的杏仁核反应性与焦虑的气质有关，并预示着以后的风险。 与青春期精神病理有关的压力适应不良反应包括 适应性前额叶-杏仁核相互作用，以及3)杏仁核CRF活性增加是 容易发展为压力诱发的精神病态。

Anxiety, depression and substance abuse are among the most common types of psychopathology that have their onset during adolescence. Anxious temperament identified during childhood is a significant risk factor for the later development of these illnesses. Since mechanistic and controlled stress exposure experiments cannot be performed in children, the proposed studies will use an extensively validated non human primate model with state of the art functional imaging and molecular methods to understand the neural circuits and molecular mechanisms underlying the adolescent vulnerability to develop stress-induced psychopathology. An important component of these studies is that they will, in young non human primates, use methods of assessment similar to those in the human studies, including functional and structural imaging, to prospectively study the interaction between increased childhood amygdala reactivity and the development of stress-induced psychopathology during adolescence. Importantly, brain tissue will be collected to assess the extent to which dysregulated amygdala corticotropin releasing factor systems underlie the adolescent vulnerability to develop anxiety and depression. It is expected that these studies will find that: 1) increased amygdala reactivity in childhood is associated with anxious temperament and predicts later risk, 2) maladaptive responses to stress that are associated with adolescent psychopathology involve failure of adaptive prefrontal-amygdala interactions, and 3) increased amygdala CRF activity underlies the vulnerability to develop stress-induced psychopathology.