While human behavioral phenotypes are invariably heterogeneous, an emerging literature supports the supposition that both genetic heritability and environmental influences contribute to behavioral conditions and disorders commonly diagnosed in children. Nevertheless, the pathways by which genetics, as well as maternal stress, depression and anxiety influence childhood behavior remain obscure. Utilizing a publically available, unbiased genome-wide association study (GWAS), we identified polymorphisms in genes associated with measures of childhood conduct problems, inattention, hyperactivity emotional symptoms, peer problems and prosocial behavior in children with ADHD. We hypothesize that maternal mental illness during pregnancy, or its pharmacological treatment, may alter the offspring's vulnerability to later psychopathology and that genetic variation will increase the offspring's risk developing childhood psychopathology. This hypothesis will be tested by examining associations of 1) polymorphisms in evidence-based candidate genes with phenotypes prospectively-evaluated, high-risk children born to women who were mentally ill during pregnancy 2) methylation patterns of those candidate genes in placental tissue with traits and behaviors measured in these children, and 3) the expression of mRNA encoded by those genes in placental tissue. This research proposal along with the didactic coursework and interaction with the multidisciplinary mentoring team provides a training platform designed to accomplish the following training goals: acquiring proficiency with 1) phenotypic characterization and the biological underpinnings of childhood psychopathology 2) the principles of bioinformatics and biostatistics as they apply to the design, conduct, and analysis of family-based association studies and 3) the technical and methodological issues related to methylation and gene expression analysis as they apply to psychiatric genetic research. Upon completion of the proposed project and the formal training described in the education plan, the candidate will have made significant progress towards initiating an independent academic career.
The children of women with mood or anxiety disorders ate at increased risk for the development of psychopathology. The examination of environmental and genetic predictors in prospectively- evaluated children will provide insight into the development of mental illness and will help to identify those requiring intervention.
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