According to the largest clinical trial to date, an intranasal version of the hormone oxytocin was no more effective than placebo in increasing social behavior in autistic children. The New England Journal of Medicine published the results today.
Researchers have been considering oxytocin as a possible treatment for autism since more than a decade, due to its role in strengthening social bonds. A few small trials suggested that the hormone might improve social skills in autistic individuals with Prader-Willi syndrome or those with low blood oxytocin levels.
The new findings, which were based on 250 autistic kids, indicate that oxytocin is not likely to be helpful, according to Evdokia Angnostou (Canada), professor of pediatrics at University of Toronto. She was not part of the new research.
According to Linmarie Sikich (associate professor of psychiatry and behavioral science at the Duke Center for Autism and Brain Development, Durham, North Carolina), the null results will change things. Many people felt that there was still a chance of this being a treatment for autism.
This type of research can be subject to publication bias. In other words, non-significant results are less likely than significant ones to be published. Daniel Quintana is a senior researcher in biological psychoiatry at University of Oslo, Norway. Quintana was not involved in this study. The new research is an important contribution to this field, he said, but does not completely discredit the idea of intranasal OXCIN being used as an autism treatment.
Measure gaps
For 24 weeks, the nasal spray contained either oxytocin (or a placebo) and was inhaled by autistic children aged 3-17 years. Participants were initially given a low dose of the hormone once daily. The participants were able to tolerate the low dose of hormone, which was administered once per day. It was gradually increased to twice daily.
Participants' parents/guardians completed a series questionnaires to rate their children's social behavior at the beginning of the trial, and again at regular intervals.
Participants in both the groups experienced improvements in social withdrawal four weeks after the trial began, according to a modified section of the Aberrant Behavior Checklist. This was the primary outcome measure. These improvements remained for the duration of the trial. Both the Pervasive Developmental Disabilities Behavior Inventory and Social Responsiveness Score measured the gains in social interaction and motivation. These results were not affected by participants' ages, verbal skills or blood levels of Oxytocin.
Anagnostou states that just giving the drug will not be enough to make a difference. Anagnostou says it is possible that the treatment improves social functionsuch as affiliation, cognition and reward. However, the questionnaires used in the new trial may not have picked up on these aspects.
A small study of intranasal Oxytocin in Phelan McDermid Syndrome children, a neurodevelopmental disorder that can often result in autism, was conducted in September. Parents reported no changes in their social behavior.
Adam Guastella is a professor of clinical psychology at Sydney University in Australia. He was not involved with either study.
Salience signal:
Researchers have gained more insight into the role of oxytocin in the brain. This has led to new ideas about how it affects social behaviour. Larry Young, the director of Emory University's Translational Center for Neuroscience in Atlanta, Georgia, was not involved in any of these studies. He says that the hormone does not enhance sociability, but rather increases the salience and impact of social stimuli. This helps people to better understand and learn from facial expressions and body movements.
Young believes that combining oxytocin therapy with some form of behavioral training could prove to be more effective in harnessing the hormones' effect as a treatment.
Anagnostou states that it is possible for some autistic individuals to still be able to respond to an oxytocin-based treatment due the heterogeneity and nature of autism. She says that although the children in the trial might have experienced different types of autism, the study didn't characterize them in this way.
Researchers believe that further research is needed to determine if administering oxytocin intramuscularly is the best way to deliver the drug into the brain. Guastella states that it is not clear if the brain takes up the hormone in this form.
Anagnostou says that even if it does, due to the way hormone levels are controlled, it might be more efficient to use a compound which activates oxytocin receptors or a parallel system within the brain than flood the brain with oxytocin.
She suggests that it is important to consider whether giving oxytocin to the system is the best method to manipulate it, or if other strategies are more appropriate.
Sikich believes that intranasal Oxytocin Treatment is unlikely to have any effect on Sociability. However, she does agree that certain genetic subtypes, such as those who are very responsive or for whom oxytocin has been completely removed, may still be able to benefit.
Multiple researchers agree that the study should be a wake-up call for parents and clinicians who are considering treating autistic children using off-label intramuscular oxytocin.
Guastella states that [the study] will appropriately dampen enthusiasm.
This story originally appeared on Spectrum.
