NCANDA Administrative Supplement for Clinical Readings and Analysis

Sri International, Menlo Park CA

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Abstract

PROJECT SUMMARY / ABSTRACT A significant outcome of prospective studies using noninvasive neuroimaging with Magnetic Resoance Imaging (MRI) is the recognition that brain structural anomalies occur even in individuals apparently free of neurological disorders. Recently, we found that 0.6% of 833 adolescent and young adult participants in a large, NIAAA- funded project (NCANDA) had anomalies identified as gray matter heterotopias. These isolated clumps of gray matter neurons located in the wrong part of the brain are thought to be associated with seizures. This incidence of heterotopias was high given that participants with a history of a seizure disorder were excluded from study. We pursued this finding by investigating heterotopia incidence in another larger NIAAA-funded project (ABCD). In a computerized search of 7,863 neuroradiological readings, 84 (1.07%) participants were identified with gray matter heterotopias. Given that heterotopias have been reported in animal models of fetal alcohol exposure, we sought to examine the relation between hetertopias and prenatal alcohol exposure in the ABCD data. Retrospective questioning of mothers of ABCD participants indicated a high incidence of heterotopias in offspring of mothers who answered in the affirmative that they had drunk alcohol while but before finding out they were pregnant. These findings raise the possibility that the incidence of heterotopias in a population enriched with fetal alcohol exposure (FAE) and fetal alcohol syndrome (FAS) should be higher than in unaffected controls and would support the inference that prenatal alcohol exposure causes heterotopias in the cortex of exposed individuals. Accordingly, in collaboration with a clinical neuroradiologist, we will oversee blind clinical readings of the MRIs of 60 FAE, 60 FAS, and 60 control subjects to seek gray matter heterotopias, in addition to other structural anomalies, in these subjects with known outcomes of prenatal alcohol exposure. Such a finding would be novel and clinically significant, serving as a warning to health-care providers of the potential of seizures and as further reason to refrain from drinking alcohol when intending to become pregnant.