Sex Differences in Early Brain Development; Brain Development in Turner Syndrome

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DESCRIPTION (provided by applicant): The goal of this K01 application is to complement the candidate's extensive background in developmental neuroendocrinology and psychology with intensive training in neuroimaging (particularly diffusion tensor imaging) and training in genetics. The training plan includes coursework, tutorials, and 2 focused research projects that will allow the candidate to succeed as an independent investigator studying the developmental mechanisms which modulate differential vulnerability to and expression of neurodevelopment disorders in each sex. Relative risk for many psychiatric disorders differs dramatically in males and females. Early-onset disorders, such as autism, occur more often in males; other conditions, such as schizophrenia, occur at similar rates in males and females, but the sexes differ in expression. It has been hypothesized that the prevalence and expression of these disorders is related to sex differences in brain development. X- chromosome effects and early exposure to gonadal hormones are strong candidates for a causal role. The aims of the research are (1) to characterize sex differences in brain development from birth to age 2; (2) to test whether brain development is altered in infants with Turner syndrome, a well-defined genetic disorder resulting from the partial or complete loss of one of the sex chromosomes. To address aim 1, high resolution MRI, including diffusion tensor imaging (DTI), will be used to characterize sex differences in brain development from birth to age 2 in a longitudinal cohort of 250 children. To address aim 2, high resolution MRI, including DTI, will be used to compare brain development in 30 infants with Turner syndrome (X monosomy) to 30 matched controls. PUBLIC HEALTH RELEVANCE: the first few years of life are the most dynamic phase of postnatal brain growth; changes in this period may be critical in the development psychiatric disorders such as autism and schizophrenia. Currently, very little is known about sexual dimorphism in this period. A better knowledge of early neurobiological sex differences and the mechanisms through which they develop is critical to understand differential vulnerability to and expression of neurodevelopment disorders in each sex. Ultimately, this will have important implications for early diagnosis and treatment. In addition, this study will provide new information on when brain abnormalities arise in Turner Syndrome and help clarify the potential role of hormone therapies in creating and/or ameliorating abnormal brain development.