The goal of this Mentored Research Career Award (K23) application is to provide training and innovative models for research on the biological, genetic and behavioral mechanisms underlying the intergenerational transmission of psychiatric risk from mother to infant. The training will provide (1) advanced education in clinical and biological research methodology, and (2) extensive, mentored research experience in assessment and interpretation of neurobiological and genetic data. The training components will include formal coursework in the University of Michigan Clinical Research Design and Statistical Analysis Program (CRDSA) under the Michigan CTSA, and extended laboratory experiences through the University of Michigan Genetics Laboratory and Trauma, Stress, and Anxiety Research Group's neurobiological and psycho-physiological laboratories. Models will be developed to study intergenerational transmission of risk, focusing on mothers with PTSD, infant's genetic risk factors, and their impact on infants'neurobiological stress regulation. Two-hundred mothers (100 PTSD-positive and 100 trauma-exposed PTSD-negative) and their 7-month old infants will be studied. Infants will be genotyped for the """"""""risk"""""""" allele polymorphisms on the serotonin transporter promoter gene, which has been robustly identified in the current literature as related to unique variation in capacity for distress regulation. Mother-infant dyads will be studied in several low-and high challenge interactions (Free Play, Teaching Task, and Still Face Paradigm) with measurement of behavioral and neurobiological stress responses (cortisol, heart rate variability). We hypothesize that (1) maternal PTSD will predict less optimal infant neurobiological stress regulation, and this link will be mediated by maternal behavior;(2) presence of genetic """"""""risk"""""""" in the infant will predict less optimal infant neurobiological stress regulation, and this relation will be moderated by maternal behavior. The combination of didactic training, mentored research experience and model development will provide the applicant with the knowledge, skills, and high quality preliminary data needed for the subsequent success as an independently funded clinical scientist, studying the complex, transactional, and longitudinal pathways of intergenerational risk transmission.
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