Psychopharmacology 3e Web Box 1.2 - Clinical Applications: Treating Autism with Intranasal Oxytocin

Oxytocin is a 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. In fact, some have called it the “love” hormone. In animal studies the hormone is injected intracerebrally, but that is 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. In healthy human subjects, oxytocin increases trust in others, enhances positive social memories, enhances attachment security, modulates memory for facial identity, and increases time spent looking at the eyes of faces, which provides socially important cues such as the other individual’s mental state. MacDonald and MacDonald (2010) summarize the prosocial effects of oxytocin and provide an evolutionary history of the hormone.

Individuals with high-functioning autism have normal language and intellectual abilities but show significant impairment in social interactions. They have particular problems in understanding and responding to social cues, so they have trouble interpreting other people’s feelings and intentions. Some show no interest in other people at all; others do not understand how to form friendships despite their desire to do so, and their social interactions are severely limited. Their inability to make rapid intuitive judgments in social situations impairs their expression of appropriate human affiliative behavior and prevents experiencing empathy with the emotions of others.

Individuals with autism and related autism spectrum disorders have lower levels of plasma oxytocin because they do not show the typical developmental increases and have reduced capacity to synthesize the hormone. Additionally, the discovery that a certain genetic polymorphism for the oxytocin receptor is more prevalent in individuals with autism and is linked to lower empathy has suggested the oxytocin hypothesis of autism. Given the effects of the neuropeptide in rodents and in healthy humans, Andari and colleagues (2010) hypothesized that oxytocin would enhance social behaviors in adults with high-functioning autism. Because eye contact is a very basic component of social skills, their behavioral measures included recording eye movement as individuals (oxytocin-treated adults with autism, placebo-treated adults with autism, and controls without autism) performed a face perception task. They found that oxytocin-treated adults with autism showed far more visual scanning of faces, especially around the eye region, than did placebo-treated adults with autism. The second measure involved decision making and emotional response during a computer-simulated ball-tossing game. Those in the placebo group did not discriminate among the conditions; that is, they showed no emotional response to the “individuals” they played with, regardless of how the fictitious players treated them. In contrast, those treated with oxytocin showed that they understood the social context of reciprocal social behavior and showed appropriate behavior and emotions.

More recent work showed that intranasal oxytocin increased the abnormal N-acetylaspartate levels in individuals with autism, which would indicate enhanced regional blood flow. In particular, they found an enhancement in neural activity and N-acetylaspartate levels in the ventromedial prefrontal cortex (vmPFC) and anterior cingulate cortex (ACC), brain regions associated with autistic deficits in empathy, emotion recognition, and theory of mind. The double-blind, crossover, controlled trial showed an enhanced ability to make social judgments based on nonverbal communication in high-functioning adults with autism. In a follow-up study the researchers concluded that oxytocin-induced enhancement of vmPFC and ACC function may not be limited to a specific cognitive task but may improve multiple autistic-like behavioral problems mediated by those brain regions (Aoki et al., 2015). Although basic research has been encouraging and some small studies suggest potential therapeutic effectiveness, the clinical trials thus far have been inconclusive, perhaps because of differences in age and severity of symptoms, doses of oxytocin tested, duration of treatment, or use of adjunctive treatment with behavior therapy. Of course, the research findings leave us hopeful for a simple-to-administer therapy for autism, but the contradictory results in clinical trials and the concerns raised about the long-term effects of oxytocin mean more research is required.

 

References

Andari, E., Duhamel, J. R., Zalla, T., Herbrecht, E., Leboyer, M., and Sirigu A. (2010). Promoting social behavior with oxytocin in high-functioning autism spectrum disorders. Proc. Natl. Acad. Sci., 107, 4389–4394.

Aoki, Y., Watanabe, T., Abe, O., Kuwabara, H., Yahata, N., Takano, Y., et al. (2015). Oxytocin’s neurochemical effects in the medial prefrontal cortex underlie recovery of task-specific brain activity in autism: A randomized controlled trial. Mol. Psychiat., 20, 447–453.

Macdonald, K. and Macdonald, T. M. (2010). The peptide that binds: A systematic review of oxytocin and its prosocial effects in humans. Harv. Rev. Psychiatry, 18, 1–21.