Browsing by Subject "Fetal Alcohol Spectrum Disorders"

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    Combined Face-Brain Morphology and Associated Neurocognitive Correlates in Fetal Alcohol Spectrum Disorders
    (Wiley, 2018-09) Suttie, Michael; Wozniak, Jeffrey R.; Parnell, Scott E.; Wetherill, Leah; Mattson, Sarah N.; Sowell, Elizabeth R.; Kan, Eric; Riley, Edward P.; Jones, Kenneth L.; Coles, Claire; Foroud, Tatiana; Hammond, Peter; Medical and Molecular Genetics, School of Medicine
    BACKGROUND: Since the 1970s, a range of facial, neurostructural, and neurocognitive adverse effects have been shown to be associated with prenatal alcohol exposure. Typically, these effects are studied individually and not in combination. Our objective is to improve the understanding of the teratogenic effects of prenatal alcohol exposure by simultaneously considering face-brain morphology and neurocognitive measures. METHODS: Participants were categorized as control (n = 47), fetal alcohol syndrome (FAS, n = 22), or heavily exposed (HE) prenatally, but not eligible for a FAS diagnosis (HE, n = 50). Structural brain MRI images and high-resolution 3D facial images were analyzed using dense surface models of features of the face and surface shape of the corpus callosum (CC) and caudate nucleus (CN). Asymmetry of the CN was evaluated for correlations with neurocognitive measures. RESULTS: (i) Facial growth delineations for FAS, HE, and controls are replicated for the CN and the CC. (ii) Concordance of clinical diagnosis and face-based control-FAS discrimination improves when the latter is combined with specific brain regions. In particular, midline facial regions discriminate better when combined with a midsagittal profile of the CC. (iii) A subset of HE individuals was identified with FAS-like CN dysmorphism. The average of this HE subset was FAS-like in its facial dysmorphism. (iv) Right-left asymmetry found in the CNs of controls is not apparent for FAS, is diminished for HE, and correlates with neurocognitive measures in the combined FAS and HE population. CONCLUSIONS: Shape analysis which combines facial regions with the CN, and with the CC, better identify those with FAS. CN asymmetry was reduced for FAS compared to controls and is strongly associated with general cognitive ability, verbal learning, and recall in those with prenatal alcohol exposure. This study further extends the brain-behavior relationships known to be vulnerable to alcohol teratogenesis.
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    Computed tomography assessment of peripubertal craniofacial morphology in a sheep model of binge alcohol drinking in the first trimester
    (Elsevier, 2015-11) Birch, Sharla M.; Lenox, Mark W.; Kornegay, Joe N.; Shen, Li; Ai, Huisi; Ren, Xiaowei; Goodlett, Charles R.; Cudd, Tim A.; Washburn, Shannon E.; Department of Medical & Molecular Genetics, IU School of Medicine
    Identification of facial dysmorphology is essential for the diagnosis of fetal alcohol syndrome (FAS); however, most children with fetal alcohol spectrum disorders (FASD) do not meet the dysmorphology criterion. Additional objective indicators are needed to help identify the broader spectrum of children affected by prenatal alcohol exposure. Computed tomography (CT) was used in a sheep model of prenatal binge alcohol exposure to test the hypothesis that quantitative measures of craniofacial bone volumes and linear distances could identify alcohol-exposed lambs. Pregnant sheep were randomly assigned to four groups: heavy binge alcohol, 2.5 g/kg/day (HBA); binge alcohol, 1.75 g/kg/day (BA); saline control (SC); and normal control (NC). Intravenous alcohol (BA; HBA) or saline (SC) infusions were given three consecutive days per week from gestation day 4-41, and a CT scan was performed on postnatal day 182. The volumes of eight skull bones, cranial circumference, and 19 linear measures of the face and skull were compared among treatment groups. Lambs from both alcohol groups showed significant reduction in seven of the eight skull bones and total skull bone volume, as well as cranial circumference. Alcohol exposure also decreased four of the 19 craniofacial measures. Discriminant analysis showed that alcohol-exposed and control lambs could be classified with high accuracy based on total skull bone volume, frontal, parietal, or mandibular bone volumes, cranial circumference, or interorbital distance. Total skull volume was significantly more sensitive than cranial circumference in identifying the alcohol-exposed lambs when alcohol-exposed lambs were classified using the typical FAS diagnostic cutoff of ≤10th percentile. This first demonstration of the usefulness of CT-derived craniofacial measures in a sheep model of FASD following binge-like alcohol exposure during the first trimester suggests that volumetric measurement of cranial bones may be a novel biomarker for binge alcohol exposure during the first trimester to help identify non-dysmorphic children with FASD.
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    POSTNATAL BRAIN DYSMORPHOLOGY INDUCED BY PRENATAL ALCOHOL EXPOSURE: A PRECLINICAL MRI STUDY
    (Office of the Vice Chancellor for Research, 2012-04-13) Ai, H.; Liang, Y.; Anthony, B.; Wetherill, L.; Ward, R.; Zhou, F.C.; CIFASD Consortium
    Brain dysmorphology is one of the most critical features of Fetal Alcohol Spectrum Disorders (FASD). This study was designed to use high resolution preclinical MRI system to compare the brain structures between alcohol exposed C57BL/6 mice with control. The objective is to examine how alcohol affects a dose- and timing-dependent brain dysmorphology during development comparable to that of human FASD. Three treated groups, ALC (pre- and pregnancy alcohol with 4.2 % (v/v) alcohol liquid), PF (pre alcohol and a calorically matched liquid pregnancy diet), and CHOW (ad lib chow/water), were examined. Mouse heads were imaged using 9.4T preclinical MRI system with 3D gradient echo (GRE) sequence to acquire volumetric images with voxel size as low as 40 microns. Whole brain, olfactory bulbs, cortex, hypothalamus, and cerebellum were segmented and the volumes were calculated. Data was examined by ANOVA followed with paired comparison between treatment groups to test the effect of prenatal alcohol exposure. ALC group had shown consistently smaller mean volumes of difference brain regions than the other two groups. Volume of total brain, olfactory bulbs and cerebellum were observed to be significantly different for ALC compared to PF pups. This indicated that prenatal alcohol exposure caused retarded fetal brain development. Comparing PF with CHOW pups, only cerebellum volume was observed to be significantly different. For cortex volume, no significant difference was shown for any pairwise comparison. These results suggest that alcohol effect contribute to brain dysmorphology, and match with our previous craniofacial dysmorphology study. This could be important to assist in the understanding of clinical variants of human FASD patients in brain dysmorphology.
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    Retinal Wnt signaling defect in a zebrafish fetal alcohol spectrum disorder model
    (PLOS, 2018-08-01) Muralidharan, Pooja; Sarmah, Swapnalee; Marrs, James A.; Biology, School of Science
    Fetal alcohol spectrum disorder caused by prenatal alcohol exposure includes ocular abnormalities (microphthalmia, photoreceptor dysfunction, cataracts). Zebrafish embryos exposed to ethanol from gastrulation through somitogenesis show severe ocular defects, including microphthalmia and photoreceptor differentiation defects. Ethanol-treated zebrafish had an enlarged ciliary marginal zone (CMZ) relative to the retina size and reduced Müller glial cells (MGCs). Ethanol exposure produced immature photoreceptors with increased proliferation, indicating cell cycle exit failure. Signaling mechanisms in the CMZ were affected by embryonic ethanol exposure, including Wnt signaling in the CMZ, Notch signaling and neurod gene expression. Retinoic acid or folic acid co-supplementation with ethanol rescued Wnt signaling and retinal differentiation. Activating Wnt signaling using GSK3 inhibitor (LSN 2105786; Eli Lilly and Co.) restored retinal cell differentiation pathways. Ethanol exposed embryos were treated with Wnt agonist, which rescued Wnt-active cells in the CMZ, Notch-active cells in the retina, proliferation, and photoreceptor terminal differentiation. Our results illustrate the critical role of Wnt signaling in ethanol-induced retinal defects.