title: Plasma oxytocin concentrations and OXTR polymorphisms predict social impairments in children with and without autism spectrum disorder.
abstract: The neuropeptide oxytocin (OXT) and its receptor (OXTR) regulate social functioning in animals and humans. Initial clinical research suggests that dysregulated plasma OXT concentrations and/or OXTR SNPs may be biomarkers of social impairments in autism spectrum disorder (ASD). We do not know, however, whether OXT dysregulation is unique to ASD or whether OXT biology influences social functioning more generally, thus contributing to, but not causing, ASD phenotypes. To distinguish between these possibilities, we tested in a child ASD cohort, which included unaffected siblings and unrelated neurotypical controls (ages 3-12 y; n = 193), whether plasma OXT concentrations and OXTR SNPs (i) interact to produce ASD phenotypes, (ii) exert differential phenotypic effects in ASD vs. non-ASD children, or (iii) have similar phenotypic effects independent of disease status. In the largest cohort tested to date, we found no evidence to support the OXT deficit hypothesis of ASD. Rather, OXT concentrations strongly and positively predicted theory of mind and social communication performance in all groups. Furthermore, OXT concentrations showed significant heritability between ASD-discordant siblings (h(2) = 85.5%); a heritability estimate on par with that of height in humans. Finally, carriers of the "G" allele of rs53576 showed impaired affect recognition performance and carriers of the "A" allele of rs2254298 exhibited greater global social impairments in all groups. These findings indicate that OXT biology is not uniquely associated with ASD, but instead exerts independent, additive, and highly heritable influences on individual differences in human social functioning, including the severe social impairments which characterize ASD.
authors.affiliation: Department of Psychiatry and Behavioral Sciences and kjparker@stanford.edu.
authors.forename: Karen J
authors.initials: KJ
authors.lastname: Parker
authors.affiliation: Department of Psychiatry and Behavioral Sciences andDepartment of Comparative Medicine, Stanford University School of Medicine, Stanford, CA 94305.
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Garner
authors.affiliation: Department of Psychiatry and Behavioral Sciences and.
authors.forename: Robin A
authors.initials: RA
authors.lastname: Libove
authors.affiliation: Department of Psychiatry and Behavioral Sciences and.
authors.forename: Shellie A
authors.initials: SA
authors.lastname: Hyde
authors.affiliation: Department of Psychiatry and Behavioral Sciences and.
authors.forename: Kirsten B
authors.initials: KB
authors.lastname: Hornbeak
authors.affiliation: Department of Psychiatry and Behavioral Sciences and.
authors.forename: Dean S
authors.initials: DS
authors.lastname: Carson
authors.affiliation: Department of Psychiatry and Behavioral Sciences and.
authors.forename: Chun-Ping
authors.initials: CP
authors.lastname: Liao
authors.affiliation: Department of Psychiatry and Behavioral Sciences and.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Phillips
authors.affiliation: Department of Psychiatry and Behavioral Sciences and.
authors.forename: Joachim F
authors.initials: JF
authors.lastname: Hallmayer
authors.affiliation: Department of Psychiatry and Behavioral Sciences and.
authors.forename: Antonio Y
authors.initials: AY
authors.lastname: Hardan
mesh_terms: D016022:Case-Control Studies; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000097:blood / Q000235:genetics / Q000523:psychology*; D002675:Child, Preschool; D005260:Female; D006801:Humans; D008297:Male; D010121:Oxytocin / Q000097:blood*; D010641:Phenotype; D011110:Polymorphism, Genetic; D018045:Receptors, Oxytocin / Q000235:genetics*; D012919:Social Behavior
chemical_list: D018045:Receptors, Oxytocin; D010121:Oxytocin
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