The Neural Effects of Oxytocin Administration in Autism Spectrum Disorders Studied by fMRI: A Systematic Review

Purpose: Oxytocin (OXT) is a hypothalamic neuropeptide that is released from the posterior pituitary gland and at specific targets in the central nervous system (CNS). The prosocial effects of OXT acting in the CNS present it as a potential therapeutic agent for the treatment of aspects of autism spectrum disorder (ASD). In this article, we systematically review the functional MRI (fMRI) literature that reports task-state and resting-state fMRI (rsfMRI) studies of the neural effects of single or multiple dose intranasal OXT (IN-OXT) administration in individuals with ASD. Method: We searched four databases for relevant documents (PubMed, Web of Science, Scopus, and Google Scholar) using the keywords “autism spectrum disorder”, “Asperger Syndrome”, “oxytocin”, and “fMRI”. Moreover, we made a manual search to assess the quality of our automatic search. The search was confined to English language articles published in the interval February 2013 until March 2021. Results: The search yielded 12 fMRI studies with OXT intervention, including 288 individuals with ASD (age 8–55 years) enrolled in randomized, double-blind, placebo-controlled, parallel designs, within-subject–crossover experimental OXT trials. Studies reporting activation task and rsfMRI were summarized with region of interest (ROI) or whole-brain voxel wise analysis. The systematic review of the 12 studies supported the proposition that IN-OXT administration alters brain activation in individuals with ASD. The effects of IN-OXT interacted with the type of the task and the overall results did not indicate restoration of normal brain activation in ASD signature regions albeit the lack of statistical evidence. Conclusion: A large body of evidence consistently indicates that OXT alters activation to fMRI in brain networks of individuals with ASD, but with uncertain implications for alleviation of their social deficits.