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

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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.