Oxytocin Improves Social Interaction in High-Functioning Adults With Autism

Pauline Anderson

February 18, 2010

February 18, 2010 — Inhaling the hormone oxytocin appears to improve social interactions in adults with high-functioning autism spectrum disorder (HF-ASD), new research suggests.

The study showed that compared with HF-ASD patients who were given placebo nasal spray, those who inhaled oxytocin could better differentiate between players who interacted with them and those who did not in a virtual ball toss game. In addition, the study also showed that oxytocin enhanced total gaze time when looking at pictures of human faces, particularly in the eye region.

Oxytocin, a hormone synthesized in the hypothalamus, plays a role in delivery and lactation and is also believed to be involved in the regulation of emotions and affiliated behavior.

The study results could eventually lead to a therapeutic approach for patients with HF-ASD, said lead author Angela Sirigu, PhD, director of research and director of the Neuropsychology Group, Institute of Cognitive Science, Centre de Neuroscience Cognitive, Lyon, France.

This gives us a hope, a potential, for a treatment, but we need to do more studies to establish how much oxytocin patients need and the effect of oxytocin over time. This study is just a start,

The study was published online February 16 in the Proceedings of the National Academy of Sciences of the United States of America.

For the study, the researchers recruited 13 adults (11 of them men) aged 17 to 39 years (mean age, 26 years) with HF-ASD or Asperger’s syndrome. These patients were of average or above average intelligence. They were free of medication for at least 2 weeks before and during the study. The study also included a group of 13 age- and sex- matched healthy controls.

Researchers measured subjects' plasma oxytocin levels. Baseline concentrations in the autism group were significantly lower than those in the control group (1.08 vs 7.28 pg/mL)

Researchers then randomly assigned each of the autism patients to receive either 24 IU of a nasal oxytocin preparation or a placebo spray. Patients acted as their own controls, receiving oxytocin and placebo separated by 1 week.

After 10 minutes, the researchers checked oxytocin levels again. They found that the levels of those who had received the treatment nasal spray increased significantly (to 2.66 pg/mL) but did not reach levels of the control group.

The subjects then performed 2 tasks. They played a virtual ball-tossing game during which the patient plays with 3 players depicted by 3 cartoon players and 3 associated pictures. The patients were led to believe that they were playing with other unidentified people sitting at computers in the same room. "We wanted the game to seem more real," explained Dr. Sirigu.

To play the game, the patient had to keep tossing the ball to another player on the screen and received 2 Euros for every toss thrown. Patients were instructed that the goal of the game was to gain as much money as possible.

However, unbeknownst to the patient, as the game progressed, the study authors manipulated the degree of cooperation to create 3 different profiles: 1 good partner who sent 70% of his balls to the patient, 1 bad partner who sent only 10% of his balls to the patient, and 1 neutral partner who shared his balls equally among all participants.

Social Rewards

Healthy patients sent significantly more balls to the "good" than to the "bad" or neutral players, whereas those in the placebo group treated all players the same. As with the healthy controls, those who had received the oxytocin nasal spray engaged more often with the "good" players.

"Under placebo, patients sent the ball to everybody; under oxytocin, they sent the ball preferentially to the 'good' players, the ones who had been good to them," said Dr. Sirigu.

Patients in the oxytocin group also reported that they trusted more and showed stronger preference for the "good" over the "bad" players.

The results suggest that the placebo group "did not take into account the behavior of other players and showed no differential emotional responses to the different players," the study authors write.

In contrast, they note, patients in the oxytocin group "engaged more often in exchanges with the player who reciprocated strongly, less often with the player who reciprocated weakly, and they exhibited emotional responses congruent with this behavior."

The investigators concluded that oxytocin "enhanced patients’ ability to process socially relevant cues and acquire their meaning in an interactive context."

The researchers repeated the experiment using the same oxytocin administration with 7 new patients with HF-ASD (mean age, 28 years) but without the monetary rewards (patients were told to play a friendly ball toss game). The results were similar, suggesting, said Dr. Sirigu, that oxytocin enhances sensitivity toward social rewards (being sent the ball) than to nonsocial rewards (money).

Total Gaze Time Increased

A second test involved visual scanning of human faces. One of the major deficits of autism is the lack of eye contact. "If patients with autism are talking to you, not only do they not look at your face, they may even turn their face in the other direction to avoid any contact," said Dr. Sirigu.

In this experiment, researchers recorded patients' eye movements while they examined pictures of faces presented one at a time on a computer screen. Patients reported whether the face was male or female and whether the person in the picture was looking straight ahead or averting his or her eyes, which "oblige" them to look at the eyes, said Dr. Sirigu.

The researchers calculated the amount of time the patient spent looking at facial features, including the eyes, nose, mouth, forehead, and cheeks and also how often they looked away from the face. They also measured the saccades (rapid displacement of the line of the gaze).

Subjects in the placebo group tended to avoid looking at the eyes, said Dr. Sirigu. When forced to look at eyes (to determine where the model was looking), these patients had abnormally high saccade frequency.

"They looked very fast as if they wanted to avoid looking in this region," said Dr. Sirigu. This finding, she said, suggests that these participants had high levels of anxiety and discomfort.

In contrast, in the oxytocin group, total gaze time over the face was relatively high, mostly because of fixation time over the eye region. This could be because the oxytocin reduced the fear or anxiety that normally would have been induced by looking at a face.

However, although the oxytocin appeared to increase gaze time on the face and eye region, it was still lower than the healthy controls.

Degrees of Social Impairment

Dr. Sirigu noted that individual performances on the face test varied, with some subjects responding strongly to oxytocin, others more weakly, and some not at all. This, she said, might be explained by different autism profiles.

Although HF-ASD is a neurodevelopmental disorder in which understanding social cues and responding to them is impaired, there are different subtypes of the disorder.

"Aloof" subjects avoid all physical contact with others, whereas "active but odd" patients can engage with others but do so in a strange or inappropriate manner. “Passive” patients (not included in this study) do not reject approaches from others but do not engage in social relationships.

“It’s possible that response to the test is dependent on the particular feature of their social disorder,” said Dr. Sirigu.

Although this study shows that oxytocin has an effect on social interactions of patients with HF-ASD, Dr. Sirigu stressed that this was under very controlled conditions. “We have to run more clinical trials to see whether it really has an effect in real life on these patients,” she said.

She added that it is important to perform other studies to show the long-term effect of oxytocin.

Recent research has implicated oxytocin in the etiology of autism, particularly the social disorders that are the hallmark of HF-ASD. One theory is that oxytocin reduces the activity of the amygdala, resulting in a decrease of fear response.

Commenting on the study, Lee Grossman, president and chief executive officer, Autism Society, said the society encourages any research that looks to improving the lives of people with autism. It is important to find treatment options that will help improve people’s quality of life today, and there are many paths that can be investigated.

The study authors have disclosed no relevant financial relationships.

Proc Natl Acad Sci U S A. Published online February 16, 2010.


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