Despite prevalent population exposure to phthalates and bisphenol A (BPA), and evidence that human neurodevelopment is likely to be altered by their potential disruption of gonadal hormones, there are few, if any, human studies of these exposures and neurodevelopment. Adolescence is a key period of vulnerability to gonadal hormones which profoundly affect not only transition to reproductive maturity, but also adolescent transition to cognitive and behavioral maturity. Underlying this adolescent transition is substantial brain organizational development and growth, including growth in brain regions demonstrating sexual dimorphisms likely related to gonadal steroid effects. In fact, brain disorders that typically start in adolescence, e.g. schizophrenia, may, in part, reflect deficient development in these areas. The primary aim of this pilot project is to assess the relation of adolescent exposure to phthalates and BPA with adolescent neurobehavior. The proposal builds on an ongoing longitudinal study of 788 children who have been followed since birth to assess the relation of early life contaminant exposures (organochlorines and metals) with subsequent neurodevelopment. The study will use this parent study's established infrastructure (including adolescent neurobehavioral exams) and wealth of existing data to address 2 new themes: (1) the potential developmental toxicities of adolescent phthalate and BPA exposures, and (2) the identification of adolescent neurobehavioral outcomes likely to be sensitive to these exposures based on: (a) experimental studies of gonadal steroids and brain function, (b) animal or human evidence of sexual dimorphism in performance, or (c) analogy with Project 4's rodent model. New data collection will be urine samples (at adolescent, 13-15 yrs neurobehavior testing) for measurement of phthalate and BPA metabolites. The relation of these exposures with psychometric measures of: visual motor abilities, verbal abilities, working memory, behaviors related to Attention Deficit Hyperactivity Disorder (ADHD), and psychiatric symptoms (e.g., depression and anxiety) will be assessed. Secondary aims will be assessment of the potential for associations of phthalates or BPA with neurobehavior to differ by sex or by pubertal status. Comparing this work with Project 4's parallel animal model will, where there is convergence, increase confidence that observed effects are, in fact, exposure related. This will be among the first studies to provide insight into the role of these compounds as risk factors for adverse neurodevelopment in adolescence, an age at high risk for exposure effects, and an age when maladaptive neurobehavioral development can be a source of substantial disability.
Despite near universal population exposure to phthalates and bisphenol A, there is a lack of human data regarding their neurodevelopmental effects. This study will provide insight into the role of these compounds as risk factors for adverse neurodevelopment in adolescence, an age at high risk for exposure effects, and an age when maladaptive neurobehavioral development can be a source of substantial disability. This will contribute to public health efforts to reduce the burden of childhood developmental disorders.
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