P50 Translational/Clinical Research Components

Photo of a toddlerP50 Component 6 Neurocognitive Markers of Fetal Alcohol Spectrum Disorders (Co-PIs: Stephen & P. Kodituwakku; Co-I: E. Kodituwakku) will extend their retrospective studies combining neurobehavioral assessment of adaptive skills, executive control and information processing combined with magnetoencephalographic (MEG) / EEG analyses of pro-saccades and a sustained attention to response task (SART) in FASD, attention deficit hyperactivity disorder (ADHD) and typically developing preadolescents, with the goal of identifying the combination of imaging and behavioral measures that optimally differentiates between these three groups.  They now have preliminary data suggesting that MEG measures are more sensitive in differentiating FASD from typically developing controls than behavioral visual prosaccade measures alone.  Furthermore, the preliminary data for the SART suggests that different electrophysiological measures differentiate FASD from controls and ADHD children, respectively.  Combined with behavioral assessments we expect these measures will help identify a unique signature of prenatal ethanol exposure to facilitate identification of alcohol-related neurodevelopmental disorder (ARND) in pre-adolescent children.

P50 Component 7 Serum MicroRNA Biomarkers of Maternal Alcohol Consumption (Co-PIs: Perrone-Bizzozero & Bakhireva; Co-Is: Savage & Rayburn) is a translational research project examining the effect of maternal drinking during pregnancy on human serum microRNA expression.  Preliminary studies have identified at least two miRNAs that are significantly altered in alcohol-consuming pregnant women.  Subjects will be recruited and classified according to Dr. Bakhireva’s screening procedure and blood samples collected at term.  Serum microRNA will be analyzed using an Affymetrix GeneChip miRNA 3.0 array and the most promising biomarker candidates will be confirmed by rt-PCR.  Subsequently, the impact of co-exposure to methadone or nicotine and the effect of ethanol exposure pattern and dose will be systematically evaluated using the mouse model of PAE.  The impact of these manipulations on “ethanol-sensitive” microRNAs will be used to help interpret the miRNA data from the clinical study, where ethanol dose and timing and co-exposures may affect the expression profiles of the panel of candidate miRNA biomarkers.

P50 Pilot Project 8A (Co-PIs: Brown & Bakhireva; Co-Is: Hall & Rayburn) will examine the effect of prenatal ethanol exposure on anatomic and functional prenatal ultrasound measures of fetal development.  Pregnant women enrolled in Dr. Bakhireva’s recruitment program and carefully screened using a combination of alcohol questionnaires and alcohol biomarkers will undergo third trimester three-dimensional ultrasound examination of fetal brain regional volumes and Doppler measures of umbilical and fetal middle cerebral artery blood flow.  This relatively novel ultrasound approach will be performed in conjunction with P50 Component 7 in an effort to build a broader array of clinical and bio-behavioral markers of prenatal ethanol exposure.  This study would also be related to Dr. Bakhireva’s and Dr. Stephen’s pending R01 proposal to conduct a short-term follow-up study of combined behavioral and functional neuroimaging responses in six- and twenty-month-old infants.