A single dose of intranasal oxytocin did not significantly enhance reward-related brain activation in men with or without autism, with Bayesian analysis providing moderate evidence for no effect.
No significant effectBayesian analysis provided moderate evidence that intranasal oxytocin genuinely had no effect on reward-related brain activation in men with or without autism — an important null finding for the field.
What the researchers found
In a randomized, double-blind, placebo-controlled crossover study of 37 men with autism and 37 controls, a single 24-IU dose of intranasal oxytocin did not significantly influence neural processes related to the anticipation of social or monetary rewards in either group.
Bayesian analyses provided moderate evidence favoring the null model over the alternative, suggesting the lack of effect is likely genuine rather than a power issue. Results were inconclusive regarding possible oxytocin effects on amygdala responsiveness to social rewards during reward consumption. Notably, there were no significant differences in reward-related brain function between autism and control groups under placebo either.
Why it matters
Oxytocin has been widely promoted as a potential treatment for social difficulties in autism, partly based on its role in social bonding. This well-designed negative study is important because it provides rigorous evidence against the hypothesis that single-dose oxytocin broadly enhances reward circuitry in autism, helping to set realistic expectations and redirect research toward more targeted approaches.
How the study worked
This was a randomized, double-blind, placebo-controlled, crossover fMRI study. Participants received either 24 IU intranasal oxytocin or placebo in separate sessions and performed an incentive delay task measuring neural activity during anticipation and receipt of both monetary and social rewards. Both frequentist and Bayesian statistical analyses were used to evaluate results.
What this study cannot tell us
The study tested only a single dose, so chronic oxytocin effects remain unknown. Only men without intellectual impairment were included, limiting generalizability to women and those with co-occurring intellectual disability. The sample size (37 per group), while reasonable, may still have been insufficient to detect subtle effects. The incentive delay task may not capture all aspects of social reward processing relevant to autism.
How to read the evidence
This is a well-designed randomized, double-blind, placebo-controlled crossover trial with both frequentist and Bayesian analyses. The methodology is strong, and the null result is well-supported. However, it tests only a single dose in a specific subpopulation of autism.
When this study was published
Published in 2022, this study contributes to a growing body of more rigorous oxytocin-autism research that has tempered initial enthusiasm about oxytocin as a treatment for social difficulties in autism.
The bigger picture
The oxytocin-autism hypothesis has generated enormous research interest and public hope. However, accumulating evidence from rigorous trials like this one suggests the relationship is more complex than initially thought. Single-dose oxytocin may not be sufficient to modulate reward circuits, pointing toward the need for different dosing regimens, longer treatment durations, or more targeted patient selection to identify who might benefit.
Questions still open
- Would repeated or chronic oxytocin dosing produce brain reward circuit changes that a single dose cannot?
- Are there subgroups within autism who might respond to oxytocin based on baseline oxytocin levels or genetic variants?
- Does the lack of reward processing differences between autism and control groups under placebo challenge fundamental assumptions about reward deficits in autism?
Common questions
Why has oxytocin been studied as a treatment for autism?
Does this mean oxytocin definitely doesn't work for autism?
Read the original research
Assessment of Reward-Related Brain Function After a Single Dose of Oxytocin in Autism: A Randomized Controlled Trial.
Biological psychiatry global open science, 2(2), 136-146
Citation
Mayer, Annalina V; Preckel, Katrin; Ihle, Kristin; Piecha, Fabian A; Junghanns, Klaus; Reiche, Stefan; Rademacher, Lena; Müller-Pinzler, Laura; Stolz, David S; Kamp-Becker, Inge; Stroth, Sanna; Roepke, Stefan; Küpper, Charlotte; Engert, Veronika; Singer, Tania; Kanske, Philipp; Paulus, Frieder M; Krach, Sören. (2022). Assessment of Reward-Related Brain Function After a Single Dose of Oxytocin in Autism: A Randomized Controlled Trial.. Biological psychiatry global open science, 2(2), 136-146. https://doi.org/10.1016/j.bpsgos.2021.10.004