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

• 批准号: 8479512
• 负责人: Tanja Jovanovic
• 金额: $ 39万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2018-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8479512
• 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; Data; Depressed mood; Development; Diagnosis; Disease; Endocrine; Environment; Environmental Risk Factor; Estrogens; Event; Exposure to; Family; Fright; Genes; Genetic; Genetic Polymorphism; Genomics; Genotype; Goals; High Risk Woman; Hormonal; Hormones; 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; base; combat; design; high risk; indexing; insight; men; neurobiological mechanism; novel; pituitary adenylate cyclase activating polypeptide; primary outcome; prospective; public health relevance; receptor; young adult

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）：低收入城市人口的高创伤暴露率和创伤后应激障碍（PTSD）强调了这一代表性不足的群体的迫切需求。在这样的样本中，可能会在生命的早期开始受到创伤的暴露。对来自类似样本的儿童和年轻人的研究表明，在儿童期或青春期期间的初始创伤暴露很常见。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在这种差异中起作用的特定遗传和内分泌因素，但这些性别差异的出现时间表仍不清楚。特别关心的是循环心理健康障碍的延续，因为沮丧或焦虑的母亲的孩子面临焦虑和抑郁本身的较高风险。危险因素包括生物学因素，例如遗传学以及环境因素，例如增加儿童创伤风险。我们最近的研究确定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。拟议的研究将使用焦虑的心理生理生物标志物来针对具有创伤和PTSD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有创伤风险的儿童中的这些生物标志物，并将在青春期后重新测试它们，以检查PTSD中性别差异的出现。我们开发了几种与PTSD相关的基于惊吓的表型。具体而言，我们发现抑制恐惧的惊吓受损是PTSD在战斗和平民创伤幸存者中的强大生物标志物。此外，黑暗增强的惊吓与PTSD有关，特别是女性，为衡量焦虑的性别差异提供了生理指数。来自学龄儿童的低收入（主要是非裔美国人城市人口）的初步数据表明，这些相同的基于惊吓的表型对发育和青春期变化敏感。