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

描述(由申请人提供)：在低收入城市人口中，创伤暴露和创伤后应激障碍(PTSD)的高比率突出了对这一代表不足的群体进行研究的迫切需要。在这样的样本中，接触创伤可能在生命早期就开始了；对来自类似样本的儿童和年轻人的研究表明，在童年或青春期最初接触创伤是很常见的。此外，女性患焦虑的风险比男性更高；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表仍然不清楚。尤其令人关切的是，精神健康障碍的循环持续存在，因为抑郁或焦虑母亲的孩子本身患焦虑和抑郁的风险更高。风险因素包括生物因素，如遗传因素，以及环境因素，如儿童创伤暴露风险增加。我们最近的研究发现，垂体腺苷酸环化酶激活多肽(PACAP)受体基因多态性是女性创伤后应激障碍的危险基因。这项拟议的研究将利用焦虑的心理生理学生物标记物，针对有创伤和创伤后应激障碍风险的儿童的相同候选基因。这项拟议的研究将在青春期前调查创伤暴露的高风险儿童中的这些生物标志物，并将在青春期后再次测试它们，以检查创伤后应激障碍中出现的性别差异。我们已经开发出几种生理的、基于惊吓的表型，它们与创伤后应激障碍相关。具体地说，我们发现，在战斗和平民创伤的幸存者中，恐惧增强的惊吓抑制受损是创伤后应激障碍的一个强有力的生物标志物。此外，黑暗强化的惊吓与创伤后应激障碍有关，尤其是在女性中，这为衡量焦虑方面的性别差异提供了一个生理指标。从学龄儿童那里收集的低收入城市人口(主要是非裔美国人)的初步数据表明，这些基于惊吓的表型对发育和青春期变化都很敏感。

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.