Intranasal oxytocin treatment for social deficits and biomarkers of response in children with autism

Abstract

Autism spectrum disorder (ASD) is characterized by core social deficits. Prognosis is poor, in part, because existing medications target only associated ASD features. Emerging evidence suggests that the neuropeptide oxytocin (OXT) may be a blood-based biomarker of social functioning and a possible treatment for ASD. However, prior OXT treatment trials have produced equivocal results, perhaps because of variability in patients' underlying neuropeptide biology, but this hypothesis has not been tested. Using a double-blind, randomized, placebo-controlled, parallel design, we tested the efficacy and tolerability of 4-wk intranasal OXT treatment (24 International Units, twice daily) in 32 children with ASD, aged 6-12 y. When pretreatment neuropeptide measures were included in the statistical model, OXT compared with placebo treatment significantly enhanced social abilities in children with ASD [as measured by the trial's primary outcome measure, the Social Responsiveness Scale (SRS)]. Importantly, pretreatment blood OXT concentrations also predicted treatment response, such that individuals with the lowest pretreatment OXT concentrations showed the greatest social improvement. OXT was well tolerated, and its effects were specific to social functioning, with no observed decrease in repetitive behaviors or anxiety. Finally, as with many trials, some placebo-treated participants showed improvement on the SRS. This enhanced social functioning was mirrored by a posttreatment increase in their blood OXT concentrations, suggesting that increased endogenous OXT secretion may underlie this improvement. These findings indicate that OXT treatment enhances social abilities in children with ASD and that individuals with pretreatment OXT signaling deficits may stand to benefit the most from OXT treatment.

Keywords: autism; biomarkers; clinical trial; oxytocin; social functioning.

Fig. 1.

The CONSORT flow diagram details the progress of participants through the double-blind, randomized, placebo-controlled 4-wk oxytocin treatment trial.

Fig. 2.

OXT treatment efficacy and biomarkers of social improvement. (A) OXT compared with placebo treatment enhances social abilities in children with ASD as measured by improvement in the trial’s primary outcome measure, the SRS. Data are presented as least squares means ± SE. (B) The pretreatment blood OXT concentration robustly predicts treatment response, such that individuals with the lowest pretreatment OXT concentrations show the greatest SRS Total Raw Score improvement. (C) Study placebo responders are identifiable by a robust posttreatment increase in blood OXT concentrations that accompany their SRS Total Raw Score improvement. Data are corrected for the blocking factors in the analysis. Placebo-treated children are depicted in blue; OXT-treated children are depicted in orange.

Fig. S1.

OXT compared with placebo treatment did not ameliorate nonsocial core or associated features of autism spectrum disorder. (A) No significant difference was observed between posttreatment repetitive behaviors as measured by the RBS-R Total Score. (B) No significant difference was observed between posttreatment anxiety symptoms as measured by the Spence Children’s Anxiety Scale Total Score. Data are corrected for the blocking factors in the analysis and are presented as least squares mean ± SE.