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

发育、创伤和基因型对儿童焦虑生物标志物的影响

基本信息

批准号：
9241440
负责人：
Tanja Jovanovic
金额：
$ 39万
依托单位：
EMORY UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-07-01 至 2019-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9241440
关键词：
Adolescence Adolescent Adult Affect African American Age Alleles Anxiety Anxiety Disorders Biological Biological Factors Biological Markers Candidate Disease Gene Child Childhood Clinical Research Darkness Data Depressed mood Development Diagnosis Disease Endocrine Environment Environmental Risk Factor Estrogens Exposure to Fright Genes Genetic Genetic Polymorphism Genomics Genotype Goals High Risk Woman Hormonal Hormones Impairment Life Literature Low income Measures Mental Depression Mental disorders Methods Methylation Minority Mothers Neurosciences Outcome Measure PACAPR-1 protein Phenotype Physiological Play Population Post-Traumatic Stress Disorders Psychopathology Psychophysiology Puberty Research Risk Risk Factors Role Sampling School-Age Population Sex Characteristics Stress Survivors Symptoms Testing Testosterone TimeLine Trauma United States Urban Population Woman Work age effect age related anxious base combat design high risk indexing insight lower income families men neurobiological mechanism novel pituitary adenylate cyclase activating polypeptide primary outcome prospective public health relevance receptor risk variant traumatic event young adult

项目摘要

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.

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）的发生率很高，这凸显了对这一代表性不足的群体进行研究的迫切需要。在这些样本中，遭受创伤的经历可能在生命早期就开始了。对类似样本的儿童和年轻人的研究表明，儿童期或青春期初次遭受创伤是很常见的。此外，女性比男性面临更高的焦虑风险；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作用，但这些性别差异出现的时间仍不清楚。特别值得关注的是周期性心理健康障碍的持续存在，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。风险因素包括遗传等生物因素以及儿童创伤暴露风险增加等环境因素。我们最近的研究发现垂体腺苷酸环化酶激活多肽 (PACAP) 受体的基因多态性是女性 PTSD 的风险基因型。拟议的研究将利用焦虑的心理生理生物标志物，针对有创伤和创伤后应激障碍风险的儿童中的相同候选基因。拟议的研究将调查青春期前遭受创伤高危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。我们已经开发出几种与 PTSD 相关的基于惊吓的生理表型。具体来说，我们发现，对于战斗和平民创伤的幸存者来说，对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，黑暗增强的惊吓与创伤后应激障碍（PTSD）相关，特别是在女性中，这为测量焦虑的性别差异提供了一个生理指标。从低收入、主要是非裔美国城市人口中收集的学龄儿童的初步数据表明，这些基于惊吓的表型对发育和青春期的变化很敏感。