Tuesday, January 19, 2016

Oxytocin nasal spray and autism

C J Yatawara, S L Einfeld, I B Hickie, T A Davenport, A J Guastella. The effect of oxytocin nasal spray on social interaction deficits observed in young children with autism: a randomized clinical crossover trial. Molecular Psychiatry. Published online October 27, 2015.


Interventions for autism are limited. The synthetic hormone oxytocin may provide a potential treatment to improve core social and behavioral difficulties in autism, but its efficacy has yet to be evaluated in young children who potentially may benefit to a greater extent. We investigated the efficacy, tolerability and safety of oxytocin treatment in young children with autism using a double-blind, randomized, placebo-controlled, crossover, clinical trial. Thirty-one children with autism received 12 International Units (IU) of oxytocin and placebo nasal spray morning and night (24 IU per day) for 5 weeks, with a 4-week washout period between each treatment. Compared with placebo, oxytocin led to significant improvements on the primary outcome of caregiver-rated social responsiveness. Overall, nasal spray was well tolerated, and the most common reported adverse events were thirst, urination and constipation. This study is the first clinical trial to support the potential of oxytocin as an early intervention for young children with autism to help improve social interaction deficits.

Inhaling the synthetic hormone oxytocin (multiple brands) led to significant improvements in social interactions in young children with autism spectrum disorder (ASD) in a randomized, double- blind crossover study conducted in Australia.

"We used some of the most widely used assessments of social responsiveness for children with autism," Adam Guastella, PhD, of the Autism Clinic for Translational Research, Brain and Mind Centre, at the University of Sydney, said in a statement.

"We found that following oxytocin treatment, parents reported their child to be more socially responsive at home, and our own blind, independent clinician ratings also supported improved social responsiveness in the therapy rooms of the Brain and Mind Centre," Dr Guastella added...

Compared with placebo, oxytocin led to significant improvements in the main primary outcome of caregiver-rated social responsiveness (P < .01). However, oxytocin had no main effect on the second primary outcome of caregiver reports of the severity of repetitive behavior.

"Significant main effects" were found for the secondary measures of caregiver-rated emotional and behavioral difficulties (P < .001). Experimenter-rated impressions of clinical global improvement were significantly greater for oxytocin compared with placebo (72% vs 41%, P < .05)...

"These findings require confirmation in larger studies," the researchers note. Studies are also needed to determine how oxytocin may improve social behavior and to document how related treatments might be used to boost established social learning interventions. Noting that they cannot rule out a placebo effect, the researchers believe future studies need to consider methods to control for placebo effects to improve detection of therapeutic responses.

Angela Sirigu, PhD, of the Institute of Cognitive Science, Centre de Neuroscience Cognitive, Lyon, France, told Medscape Medical News these results are "encouraging and important because the trial was in children, and it shows that oxytocin has a beneficial cumulative effect. They are not novel since we have already shown (in our 2010 paper in PNAS) that oxytocin alleviates the social impairments of autistic (adult) patients. Therefore, I am happy to see these findings confirming ours.

"The only criticism I have is they used subjective scales only to document the improvement. They don't have rigorous lab testing, such as tasks known to be sensitive to oxytocin effects. Otherwise, I think it is an important addition to the oxytocin literature and autism," Dr Sirigu said.

Evdokia Anagnostou, MD, clinician scientist, University of Toronto, Canada, who was not involved in the study, agrees.

"This is a very promising randomized controlled trial in young children with ASD. Given the paucity of any medications treating the social core deficits of ASD, these are encouraging data, but larger studies will be necessary," Dr Anagnostou told Medscape Medical News.




  1. Andari E, Duhamel JR, Zalla T, Herbrecht E, Leboyer M, Sirigu A. Promoting social behavior with oxytocin in high-functioning autism spectrum disorders. Proc Natl Acad Sci U S A. 2010 Mar 2;107(9):4389-94.


    Social adaptation requires specific cognitive and emotional competences. Individuals with high-functioning autism or with Asperger syndrome cannot understand or engage in social situations despite preserved intellectual abilities. Recently, it has been suggested that oxytocin, a hormone known to promote mother-infant bonds, may be implicated in the social deficit of autism. We investigated the behavioral effects of oxytocin in 13 subjects with autism. In a simulated ball game where participants interacted with fictitious partners, we found that after oxytocin inhalation, patients exhibited stronger interactions with the most socially cooperative partner and reported enhanced feelings of trust and preference. Also, during free viewing of pictures of faces, oxytocin selectively increased patients' gazing time on the socially informative region of the face, namely the eyes. Thus, under oxytocin, patients respond more strongly to others and exhibit more appropriate social behavior and affect, suggesting a therapeutic potential of oxytocin through its action on a core dimension of autism.

  2. See above. 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.

    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)...

    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.

    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."

    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. (continued)

  3. (continued)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.

    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.