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Oxytocin is a peptide hormone manufactured in the hypothalamus and released by the pituitary that has numerous peripheral effects on reproductive events, including facilitating birth and lactation. In addition, it acts as a modulator of nerve cell function within the brain and is involved in regulation of emotion. In particular, oxytocin injected into the brain of rodents enhances monogamous pair-bonding, maternal–infant attachment, and approach behavior including sexual activity. Because oxytocin (along with most other peptides) does not efficiently cross the blood-brain barrier, the hormone is typically injected directly into the brain in animal studies. However, that is obviously an unrealistic approach to human therapeutics. Instead, to test the central effects of oxytocin on human behavior, intranasal administration has been used to bypass the blood–brain barrier. Many studies of this kind have been performed with healthy human participants, and although the early studies seemed to indicate that oxytocin exerted a wide variety of prosocial effects, over time the field has become more controversial because of conflicting results. Nonetheless, there is at least some evidence supporting a positive role for oxytocin in social cognition (including emotion recognition) and cooperation (Leppanen et al., 2017; Horta et al., 2020; Yang et al., 2021).
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by major impairments in social communication. Children diagnosed with ASD have particular problems in understanding and responding to social cues, including an inability to experience empathy with the emotions of others. This leads to difficulty interpreting other people’s feelings and intentions. Some individuals with ASD show no interest in other people at all; others do not understand how to form friendships despite their desire to do so, thus leading to severe limitations in their social interactions.
Based on the evidence from both animal and human studies implicating oxytocin in social behaviors, scientists have hypothesized that deficits in the oxytocin system may underlie at least some cases of ASD and, therefore, that social communication might be improved by intranasal oxytocin administration. Parker and colleagues (2017) tested the efficacy of intranasal oxytocin using a double-blind, randomized, placebo-controlled study of 32 children, aged 6-12 years, all diagnosed with ASD. Children in the treated group (n=14) were administered oxytocin nasal spray twice daily for 4 weeks. Controls (n=18) received a placebo spray containing the identical drug vehicle but with no oxytocin present. Compared to placebo, oxytocin treatment led to a significant improvement in scores on the Social Responsiveness Scale. Moreover, the researchers also measured plasma oxytocin levels before and after the treatment, and children with low pretreatment oxytocin showed the greatest benefit from receiving the hormone.
Although the results from this particular study seem to be quite encouraging, there are enough negative findings (i.e., no beneficial effect of oxytocin) to go along with the positive ones that scientists are not yet able to conclude that oxytocin is a useful medication for treating ASD (see Chapter 3 for additional discussion of ASD and the effects of oxytocin on social behaviors). Since the study of Parker et al. (2017) found the greatest improvement in children with low oxytocin levels, perhaps this factor needs to be taken into account more consistently in future research. Sex differences in the behavioral effects of oxytocin have also begun to emerge and should be considered when analyzing experimental results. Lastly, scientists need to improve the methodology of intranasal administration of oxytocin and other medications, to ensure that there is adequate delivery of the drug to the brain (Erdő et al., 2018; Quintana et al., 2021; Winterton et al., 2021). Considering that there are no medications currently approved for treating the social communication deficits in children with ASD, hope remains that oxytocin or perhaps a synthetic derivative of this hormone may yet be proven to have therapeutic efficacy when given under the right conditions.
References
Erdő, F., Bors, L.A., Farkas, D., Bajza, A., and Gizurarson, S. (2018). Evaluation of intranasal delivery route of drug administration for brain targeting. Brain Res. Bull., 143, 155–170.
Horta, M., Pehlivanoglu, D., and Ebner, N.C. (2020). The role of intranasal oxytocin on social cognition: An integrative human lifespan approach. Curr. Behav. Neurosci. Rep., 7, 175–192.
Leppanen, J., Ng, K.W., Tchanturia, K., and Treasure, J. (2017). Meta-analysis of the effects of intranasal oxytocin on interpretation and expression of emotions. Neurosci. Biobehav. Rev., 78, 125–144.
Parker, K.J., Oztan, O., Libove, R.A., Sumiyoshi, R.D., Jackson, L.P., Karhson, D.S., Summers, J.E., et al. (2017). Intranasal oxytocin treatment for social deficits and biomarkers of response in children with autism. Proc. Natl. Acad. Sci. USA, 114, 8119–8124.
Quintana, D.S., Lischke, A., Grace, S., Scheele, D., Ma, Y., and Becker, B. (2021). Advances in the field of intranasal oxytocin research: lessons learned and future directions for clinical research. Mol. Psychiatry, 26, 80–91.
Winterton, A., Westlye, L.T., Steen, N.E., Andreassen, O.A., and Quintana, D.S. (2021). Improving the precision of intranasal oxytocin research. Nat. Hum. Behav., 5, 9–18.
Yang, X., Wang, W., Wang, X.T., and Wang, Y.W. (2021). A meta-analysis of hormone administration effects on cooperative behaviors: Oxytocin, vasopressin, and testosterone. Neurosci. Biobehav. Rev., 126, 430–443.