The autism spectrum disorders (ASDs) are a heterogeneous group of developmental disorders with specific core features, including impaired social interaction and abnormal repetitive behavior. Several ongoing studies, including our own, are assessing the use of the drug oxytocin to ameliorate social deficits in individuals with ASDs and other psychosocial disorders. We hypothesize that behavioral response to oxytocin treatment is mediated by genetic and epigenetic factors and that these factors, particularly epigenetic mediators of gene expression, may be pivotal to baseline response and/or may change during oxytocin exposure. This proposal will explore the role of the epigenome and genetic predisposition to oxytocin treatment response in longitudinal samples that have already been collected as part of an ongoing clinical trial in high and low functioning children with ASDs; we will investigate the transcriptome and epigenome (5mC and 5hmC) in regions of the brain and periphery of a mouse model of ASD known to have positive response to oxytocin treatment; we will also examine novel regulatory mechanisms of oxytocin's receptor OXTR via 5-hydroxy methyl cytosine. The data generated by these aims will not only serve to develop (epi)genetic predictors of oxytocin response, but they will inform other trials using oxytocin to treat psychosocial disorders.

Public Health Relevance

The autism spectrum disorders (ASDs) are a heterogeneous group of developmental disorders with specific core features, including impaired social interaction and abnormal repetitive behavior. Several ongoing studies, including our own, are assessing the use of the drug oxytocin to ameliorate social deficits in children with ASDs. This proposal will explore the role of the epigenome and genetic predisposition to oxytocin treatment response in humans and an established animal model of oxytocin response, and will identify novel regulatory mechanisms of oxytocin's receptor OXTR.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD088007-05
Application #
10105203
Study Section
Pathophysiological Basis of Mental Disorders and Addictions Study Section (PMDA)
Program Officer
Kau, Alice S
Project Start
2017-02-14
Project End
2022-01-31
Budget Start
2021-02-01
Budget End
2022-01-31
Support Year
5
Fiscal Year
2021
Total Cost
Indirect Cost
Name
Duke University
Department
Neurology
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
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