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Identifying Genetic and Epigenetic Signatures of Treatment Response to Oxytocin in Humans and Mice

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Siecinski, Stephen

Gregory, Simon

Duke University

$60,800.00

2 years

Weatherstone Predoctoral Fellowship

Durham

North Carolina

United States

2016

http://www.duke.edu

https://plu.mx/autismspeaks/grant/autismspeaks-10136

The SOARS-B clinical trial is evaluating the use of intranasal oxytocin (OT) in a large cohort of high and low functioning individuals with ASD. Previous research demonstrates the prosocial effects of exogenous OT in both humans and animal models, and SOARS-B aims to use the neuropeptide to address core social deficits of ASD via a 48 week twice-daily treatment course. I will profile genome-wide expression and DNA-methylation from participant blood samples to identify predictive biomarkers of treatment response and how these profiles are altered during treatment course. I will also genotype all participants for single nucleotide polymorphisms in the oxytocin signaling pathway which have been previously associated with social deficits, to determine their specific interactions with OT treatment. We also will use established mouse models to observe brain region specific effects of OT in socially deficient mice (C58J), and how dysregulation of DNA-methylation plasticity interacts with OT treatment and normal social development (C57BL/6-TET1-KO). This unique combination of a large clinical cohort, chronic OT treatment and detailed genetic / epigenetic studies, paired with behavioral profiling of both human and model systems, will significantly improve our ability to identify clinical biomarkers from SOARS-B while further developing our understanding of the mechanistic impacts of chronic OT exposure in both blood and the socially relevant brain regions.

Multivariate Analyses, Expression Profiling, Epigenetics, Biomarkers, Genetics, Clinical Trial, Association Analysis, Biology, Screening/ Diagnosis/ Phenotyping, Treatment/ Prevention, Children (3-12 Years), Adolescents/ Young Adults (13-25 Years), Autism Spectrum Disorder, Aspergers/ High-Functioning Individuals With ASD, Low-Functioning/ Non-Verbal Individuals With ASD, Mice

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