Browsing by Author "Wozniak, Jeffrey R."

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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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    Facial Curvature Detects and Explicates Ethnic Differences in Effects of Prenatal Alcohol Exposure
    (Wiley, 2017) Suttie, Michael; Wetherill, Leah; Jacobson, Sandra W.; Jacobson, Joseph L.; Hoyme, H. Eugene; Sowell, Elizabeth R.; Coles, Claire; Wozniak, Jeffrey R.; Riley, Edward P.; Jones, Kenneth L.; Foroud, Tatiana; Hammond, Peter; Department of Medical & Molecular Genetics, IU School of Medicine
    Background Our objective is to help clinicians detect the facial effects of prenatal alcohol exposure by developing computer-based tools for screening facial form. Methods All 415 individuals considered were evaluated by expert dysmorphologists and categorized as (i) healthy control (HC), (ii) fetal alcohol syndrome (FAS), or (iii) heavily prenatally alcohol exposed (HE) but not clinically diagnosable as FAS; 3D facial photographs were used to build models of facial form to support discrimination studies. Surface curvature-based delineations of facial form were introduced. Results (i) Facial growth in FAS, HE, and control subgroups is similar in both cohorts. (ii) Cohort consistency of agreement between clinical diagnosis and HC-FAS facial form classification is lower for midline facial regions and higher for nonmidline regions. (iii) Specific HC-FAS differences within and between the cohorts include: for HC, a smoother philtrum in Cape Coloured individuals; for FAS, a smoother philtrum in Caucasians; for control-FAS philtrum difference, greater homogeneity in Caucasians; for control-FAS face difference, greater homogeneity in Cape Coloured individuals. (iv) Curvature changes in facial profile induced by prenatal alcohol exposure are more homogeneous and greater in Cape Coloureds than in Caucasians. (v) The Caucasian HE subset divides into clusters with control-like and FAS-like facial dysmorphism. The Cape Coloured HE subset is similarly divided for nonmidline facial regions but not clearly for midline structures. (vi) The Cape Coloured HE subset with control-like facial dysmorphism shows orbital hypertelorism. Conclusions Facial curvature assists the recognition of the effects of prenatal alcohol exposure and helps explain why different facial regions result in inconsistent control-FAS discrimination rates in disparate ethnic groups. Heavy prenatal alcohol exposure can give rise to orbital hypertelorism, supporting a long-standing suggestion that prenatal alcohol exposure at a particular time causes increased separation of the brain hemispheres with a concomitant increase in orbital separation.
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    Persistent Changes in Stress-Regulatory Genes in Pregnant Women or Children Exposed Prenatally to Alcohol
    (Wiley, 2019-07-22) Sarkar, Dipak K.; Gangisetty, Omkaram; Wozniak, Jeffrey R.; Eckerle, Judith K.; Georgieff, Michael K.; Foroud, Tatiana M.; Wetherill, Leah; Wertelecki, Wladimir; Chambers, Christina D.; Riley, Edward; Zymak-Zakutnya, Natalya; Yevtushok, Lyubov; Medical and Molecular Genetics, School of Medicine
    Background: We have recently shown that binge or heavy levels of alcohol drinking increases DNA methylation and reduces gene expression of POMC and PER2 in adult human subjects (Gangisetty et al., 2019). One hypothesis would be that methylation of these two genes is consistently associated with alcohol exposure and could be used as biomarkers to predict risk of PAE. Results of the present study provided some support for this hypothesis. Methods: We conducted a series of studies to determine DNA methylation changes in stress regulatory genes proopiomelanocortin (POMC) and period 2 (PER2) using biological samples from three separate cohorts of patients i) pregnant women who consumed moderate to high levels of alcohol or low/unexposed controls, ii) children with PAE and non-alcohol exposed controls, and iii) children with PAE treated with or without choline. Results: We found pregnant women who consumed moderate to high levels of alcohol and gave birth to PAE children had higher DNA methylation of POMC and PER2. PAE children also had increased methylation of POMC and PER2. The differences in the gene methylation of PER2 and POMC between PAE and controls did not differ by maternal smoking status. PAE children had increased levels of stress hormone cortisol and adrenocorticotropic hormone (ACTH). Choline supplementation reduced DNA hypermethylation and increased expression of POMC and PER2 in children with PAE. Conclusions: These data suggest that PAE significantly elevates DNA methylation of POMC and PER2 and increases levels of stress hormones. Furthermore, these results suggest the possibility that measuring DNA methylation levels of PER2 and POMC in biological samples from pregnant women or from children may be useful for identification of a woman or a child with PAE.