Development, Trauma, and Genotype Effects on Biomarkers of Anxiety in Children

描述（由申请人提供）：低收入城市人口中创伤暴露和创伤后应激障碍（PTSD）的高发病率强调了在这一代表性不足的群体中进行研究的迫切需要。在这些样本中，创伤暴露可能在生命早期就开始开始;对来自类似样本的儿童和年轻人的研究表明，儿童或青春期的初始创伤暴露是常见的。此外，女性比男性更容易焦虑;尽管一些新的研究表明，特定的遗传和内分泌因素在这种差异中发挥了作用，但这些性别差异出现的时间轴仍不清楚。特别令人关切的是，心理健康疾病的周期性持续存在，因为抑郁或焦虑母亲的子女本身患焦虑和抑郁的风险更高。风险因素包括遗传等生物因素以及环境因素，如儿童创伤暴露的风险增加。我们最近的研究确定了垂体腺苷酸环化酶激活多肽（PACAP）受体的基因多态性作为女性PTSD的风险基因型。这项拟议中的研究将利用焦虑的心理生理学生物标志物，针对有创伤和创伤后应激障碍风险的儿童的同一候选基因。这项拟议的研究将调查青春期前创伤暴露高风险儿童的这些生物标志物，并将在青春期后再次对其进行重新测试，以检查PTSD中性别差异的出现。我们已经开发了几种与PTSD相关的生理性、基于惊吓的表型。具体来说，我们已经发现，在战斗和平民创伤的幸存者中，恐惧增强惊吓的抑制受损是PTSD的一个强有力的生物标志物。此外，黑暗增强惊吓与PTSD相关，特别是在女性中，为测量焦虑的性别差异提供了生理指标。从学龄儿童收集的低收入，主要是非洲裔美国人的城市人口的初步数据表明，这些相同的startle-based表型是敏感的发展以及青春期的变化。

DESCRIPTION (provided by applicant): High rates of trauma exposure and post-traumatic stress disorder (PTSD) in low-income, urban populations underscore the urgent need for research in this under-represented group. In such samples, exposure to trauma may begin early in life; studies of children and young adults from similar samples suggest that initial trauma exposure during childhood or adolescence is common. In addition, women are at higher risk for anxiety than men; although some new research indicates specific genetic and endocrine factors that play a role in this difference, the timeline of emergence of these sex differences are still unclear. Of particular concern is the perpetuation of the cycle mental health disorders, in that children of depressed or anxious mothers are at higher risk of developing anxiety and depression themselves. Risk factors include biological factors such as genetics as well as environmental factors, such as increased risk of child trauma exposure. Our recent study identified a gene polymorphism of the pituitary adenylate cyclase-activating polypeptide (PACAP) receptor as a risk genotype for PTSD in women. The proposed study will target the same candidate gene in children at risk for trauma and PTSD, using psychophysiological biomarkers of anxiety. The proposed study will investigate these biomarkers in children at high risk for trauma exposure prior to puberty and will re-test them again after puberty in order to examine the emergence of sex differences in PTSD. We have developed several physiological, startle-based phenotypes that are related to PTSD. Specifically, we have found that impaired inhibition of fear-potentiated startle is a robust biomarker of PTSD in survivors of combat and civilian trauma. Furthermore, dark-enhanced startle is associated with PTSD specifically in women, providing a physiological index for measuring sex differences in anxiety. Preliminary data from a low-income, primarily African American urban population collected from school-age children indicate that these same startle-based phenotypes are sensitive to developmental as well as pubertal changes.