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Grant Abstract: Longitudinal neuroprotective effects of periconceptional folic acid supplements in help-seeking youth with psychiatric symptoms and healthy controls

Grant Number: 1R01MH120402-01A1
PI Name: Roffman
Project Title: Longitudinal neuroprotective effects of periconceptional folic acid supplements in help-seeking youth with psychiatric symptoms and healthy controls

Abstract: The prenatal environment contributes substantially to risk for serious mental illnesses that can emerge decades after birth. As such, prenatal life may be a propitious time to intervene in ways that reduce risk. Indeed, replicated, robust evidence from recent public health studies associates early prenatal exposure to folic acid with an approximately 50% reduction in autism risk. Further, our recent work associated increased fetal exposure to population-wide folic acid fortification of grain products with specific changes in brain development, characterized by delayed thinning of the cerebral cortex during adolescence and associated reduction in risk for psychosis symptoms. These changes were most pronounced in regions subserving frontoparietal control and limbic networks, which have been broadly implicated across categories of psychiatric illness, and specifically linked to variation in blood folate levels in healthy adults and patients with schizophrenia by our group. These findings are unprecedented, and of potentially substantial PUBLIC HEALTH RELEVANCE: The fetal environment substantially influences risk for severe mental illnesses (SMI), some of which do not fully emerge until early adulthood. The proposed studies will build upon our previous cross-sectional work suggesting that increased exposure to folic acid during early pregnancy confers protection against postnatal SMI risk through longitudinal effects on cerebral cortical development. We will conduct prospective MRI, clinical, and cognitive assessments of children who are at clinical high risk for SMI, to determine whether exposure to folic acid supplements early in pregnancy favorably alters their neurodevelopmental trajectories and risk for psychopathology in adolescence, and explore neural mechanisms that could mediate these effects.

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