Plasma Oxytocin and Vasopressin Concentrations In Autism Spectrum Disorders

Background: The neuropeptides oxytocin and vasopressin are critically involved in social behavior and social cognition in animals. Impairments in social functioning are the defining, core feature of autism spectrum disorders (ASD), but at present, no widely applicable neurochemical markers with diagnostic or prognostic utility have been identified. Preliminary research using small study samples of mostly male participants suggests that plasma oxytocin and vasopressin levels are abnormal in individuals with ASD compared to typically developing control individuals. Here we extend this initial work to investigate plasma concentrations of both neuropeptides in a large and well characterized case-control study cohort which includes female subjects and siblings of individuals with ASD.

Objectives: The aims of this research were two-fold: (1) test whether abnormalities in plasma neuropeptide levels were most pronounced in children with ASD compared to typically developing control children, and intermediate in their siblings, consistent with the notion of a broader autism phenotype and (2) test whether plasma neuropeptide levels were associated with social functioning.

Methods: Participants included children with ASD (N=50 males and 16 females), their siblings (N=36 males and 19 females), and typically developing control children (N=29 males and 25 females) between 3 and 12 years of age. An extensive behavioral phenotype battery was completed on all subjects. Autism diagnosis was based on the Autism Diagnostic Observation Schedule, Autism Diagnostic Interview-Revised, and expert clinical opinion. Blood samples were collected from all subjects and oxytocin and vasopressin concentrations were subsequently quantified using commercially available enzyme immunoassays after solid phase extraction.

Results: There was a significant difference in plasma oxytocin concentrations between experimental groups (p=0.02). Specifically, male children with ASD exhibited elevated plasma oxytocin concentrations compared to male control children (p=0.04). Oxytocin levels in male siblings were intermediate, and did not differ from either group. No significant group differences in plasma oxytocin levels were found for female subjects, nor were any group differences observed for plasma vasopressin concentrations. We performed sparse canonical correlation analysis between neuropeptide levels and behavioral phenotypes and identified a set of social variables that were maximally correlated with neuropeptide levels in all study subjects.  

Conclusions: This research implicates a possible role for oxytocin, but not vasopressin, as a neurochemical marker of the social impairments in ASD. While our experimental findings need to be replicated in a larger cohort of female subjects, these preliminary findings suggest that a better understanding of oxytocin biology may ultimately lead to improved diagnostic and possibly therapeutic approaches for children with autism.