Perinatal risk factors and genetic susceptibility for childhood psychopathology

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DESCRIPTION (provided by applicant): A notable recent advance in psychiatry is the recognition that mental health problems can originate in-utero. Research in developmental psychopathology has shown that preterm birth is associated with a 2- to 3-fold increased risk of both disruptive behavior and anxiety disorders. However, no prior studies have examined why preterm birth is associated with a wide range of childhood disorders. Furthermore, few studies have integrated models based on research in perinatal epidemiology and psychiatric genetics to understand the trajectory of developmental psychopathology. The purpose of this Mentored Research Scientist Development Award (K01) is to support the development of the candidate to become an independent scientist whose work will focus on the impact of modifiable prenatal predictors on mental illness, taking into account genetic influences. To achieve this goal, the candidate's multidisciplinary group of mentors will teach her specific methods for studying fetal/child development and psychiatric genetics, and guide her selection of coursework. For the candidate successfully integrate these disparate scientific disciplines, the team of mentors will actively monitor and review the candidate's progress. The research plan was significantly refined and simplified, and proposes a program of research comprised of two related studies: 1) a longitudinal epidemiologic study of 2,022 children who were enrolled in the National Collaborative Perinatal Study - New England and followed into adulthood and 2) a longitudinal study of 225 children at high and low risk for Attention Deficit Hyperactivity Disorder. Two competing hypotheses will be tested: (1) that different causes of preterm birth independently influence the risk of disruptive behavior and anxiety disorders; and (2) that preterm birth, regardless of its cause, interacts with genetic susceptibility to directly increase the risk for each disorder. In this revised application, genetic and epigenetic training at Jackson Lab is proposed in a place of the additional longitudinal statistics workshop. As a part of the training, the candidate will conduct retrospective data collection to gather supplemental information on the early developmental environment during pregnancy while maximizing the infrastructure available in the second study. This research has significant public health implications in helping to elucidate the developmental, biological, and genetic pathways through which childhood disorders develop. Subsequent identification of very early modifiable risk factors for childhood disorders will create new possibilities for earlier and more effective interventions. This may help relieve the burden in families with young children exhibiting psychopathology by informing new treatment approaches for young children. Together, this research and training program will effect the candidate's transition to independence as an investigator and will contribute greatly to our understanding of modifiable risk factors for disruptive behavior and anxiety disorders for planning and testing future interventions.