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Oxytocin and Vasopressin in Autism: Why All the Excitement?

New research provides insight into the role of neuropeptides.

In the last two decades, interest in the neuropeptides oxytocin (OXT) and arginine vasopressin (AVP) has dramatically increased. Why are these brain chemicals of interest in autism spectrum disorder (ASD), and what does recent research say about the topic?

Interest in OXT and AVP, both chemicals released by the pituitary gland, began with findings from animal research, which suggested an important role in romantic bonds, social recognition, and aggressive behaviors. In humans, these chemicals are also implicated in complex social behaviors such as: social stress, social cognition, trust, social approach, and aggression. Given the link between OXT and AVP with social behavior, numerous studies have explored the role of these chemicals in autism, and brain research in the past few years has yielded particularly interesting results.

Neuroscience studies suggest that intranasal OXT (oxytocin delivered via nasal spray) increases response to social stimuli in ASD and increases connectivity between brain regions involved in reward and social/emotional processing. This is exciting, as it directly measures the effect of OXT on the brain in ASD. However, a frustrating problem for autism researchers trying to understand the role of AVP and OXT is lack of high-quality animal models of autism. Although we can study the effects of a single dose of OXT on social perception, that is a far cry from understanding how (and if) OXT or AVP could work as a direct intervention for autism.

Animal models are the most effective way to explore that type of question. Unfortunately, animal models in ASD are largely confined to mouse models—which, although useful for a variety of research questions, are problematic for a few reasons. The most important shortcoming of mouse models in ASD is that mice do not naturally engage in the same social behaviors that are impaired in ASD.

This file is licensed under the Creative Commons Attribution-Share Alike 4.0 International license.
Source: This file is licensed under the Creative Commons Attribution-Share Alike 4.0 International license.

A new paper, published last month in Science Translational Medicine, may move us in the direction of a more accurate animal model and help us understand the role of neuropeptides in ASD. The authors observed rhesus monkeys, an extremely social species, to explore whether less social monkeys had biological differences (compared to highly social monkeys) in AVP and OXT. They found that AVP concentrations were significantly lower in less social than in highly social monkeys. The authors then replicated this finding (the difference in AVP concentrations) in a new set of monkeys. Finally, the authors replicated these findings in children with and without ASD (using previously collected samples of cerebrospinal fluid). Similar to the findings in monkeys, concentration of AVP were used to accurately distinguish between children diagnosed with ASD and neurotypical children.

In my view, the most exciting part of these findings is underscoring the potential role of AVP in social behavior. Taken alongside previous research mentioned above, it suggests that both AVP and OXT likely play a role in social behaviors in ASD. I wrote a review paper about the role of OXT in social reward and interaction in ASD, and stated that I hoped future research would try pairing OXT with behavioral intervention to optimize outcome. I continue to hope that research moves in that direction, as increasing OXT and AVP alone would likely be less effective than pairing AVP or OXT with behavioral interventions.

However, it is important to be aware of the limitations of this research, and recognize that we do not recommend giving either OXT or AVP to children outside of research. It is critical to wait for future work to validate these findings and to make sure that these neuropeptides can be used safely and effectively. I am optimistic about the role of these chemicals in translational research and look forward to what comes next.