Perinatal risk factors and genetic susceptibility for childhood psychopathology

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DESCRIPTION (provided by applicant): One remarkable recent advance in psychiatry is the recognition that mental health problems can originate in utero. Research in developmental psychopathology has shown that preterm birth (PTB) is associated with a 2- to 3-fold increased risk of both disruptive behavior and anxiety disorders. However, no prior studies have examined why PTB 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 an independent scientist, whose work will be devoted to the examination of perinatal problems that are related to modifiable prenatal predictors of mental illness, taking into account genetic influences. To achieve this goal, in this revised application, the candidate has strengthened her multidisciplinary group of mentors reflecting a more focused program of research. They will teach her specific methods for studying fetal/child development and psychiatric genetics, and monitor her coursework. For the candidate to have a successful integration of apparently disparate disciplines, plans for the team of mentors to monitor and review the candidate's progress have been put in place. As suggested in the previous set of reviews, the research plan was significantly refined and simplified to test two competing hypotheses: (1) that different causes of PTB independently influence the risk of disruptive and anxiety disorders; and (2) that PTB, regardless of its cause, interacts with genetic susceptibility to directly increase the risk for each disorder. The research plan proposes a program of research comprised two related studies: 1) a longitudinal epidemiologic study of 2,022 children (Study 1) who were enrolled in the National Collaborative Perinatal Study - NewEngland and followed into adulthood and 2) a longitudinal study of 225 children at high and low risk for Attention Deficit Hyperactivity Disorder (Study2). Additionally, retrospective data collection of early developmental environment during pregnancy from mothers is included, where the candidate will collect her own data to test her hypotheses maximizing the infrastructure available in Study 2. This research has significant public health implications. First, it will help 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. That may help relieve the burden in families with young children who have developmental psychopathology as well as providing new possibilities for treatment of the children themselves. Together, the research and training program are central to the candidate's transition to independence as an investigator and will contribute greatly to our understanding of modifiable risk factors for disruptive and anxiety disorders for future interventions.