October 13, 2021


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Tags: Autism, ineffective, Intranasal, Large, Oxytocin, Spectrum, trial


Categories: autism

Intranasal oxytocin ineffective for autism in massive trial | Spectrum

Placebo Effect: According to a new study, intranasal oxytocin is unlikely to increase sociability in most autistic children.

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An intranasal form of the hormone oxytocin is no more effective than placebo at improving social behavior in autistic children, according to perhaps the largest clinical study of the treatment to date. The results were published today in The New England Journal of Medicine.

Because of oxytocin’s role in strengthening social bonds, researchers have viewed it as a treatment candidate for autism for more than a decade. Small studies suggested that the hormone could improve the social skills of some autistic people, such as:

But the new results, based on 250 autistic children, suggest that “oxytocin, at least in its current form, is unlikely to be helpful for the majority of children with autism,” says Evdokia Anagnostou, professor of pediatrics at the University of Toronto in Canada. who was not involved in the new work.

The null results “change things,” says lead researcher Linmarie Sikich, associate professor of psychiatry and behavioral science at the Duke Center for Autism and Brain Development in Durham, North Carolina. “Most people still felt that this would be a good opportunity for many people with autism.”

This type of research is prone to publication bias, where insignificant results are less likely to be published than significant ones, says Daniel Quintana, a senior researcher in biological psychiatry at the University of Oslo in Norway who was not involved in the study. For this reason, the new work is “an important contribution in this area”, he says, “but it does not by itself destroy the idea of ​​using intranasal oxytocin to treat autism”.

Measure gaps:

The autistic children in the study, ages 3 to 17, inhaled a nasal spray containing either oxytocin or a placebo for 24 weeks. Participants started with a low dose of the hormone given once a day. When this dose was well tolerated, it was gradually increased over time to a higher dose twice a day.

The participants’ parents or guardians completed a series of questionnaires to assess their child’s social behavior at the start of the study and at regular intervals thereafter.

Four weeks into the study, participants in both groups showed improvements in social withdrawal according to a modified part of the Aberrant Behavior Checklist, the primary endpoint of the study. These changes persisted for the remainder of the process. Both groups also showed increases in sociability and social motivation, as measured by the Pervasive Developmental Disorders Behavior Inventory and the Social Responsiveness Scale. Results did not vary with participants’ age, verbal ability, or blood oxytocin levels.

“Simply giving the drug is probably not enough to make a difference,” says Anagnostou. However, she adds that treatment may improve other aspects of social functioning – such as association, cognition, belonging, and reward – that the new study questionnaires may not capture.

In September, a small study of intranasal oxytocin in children with Phelan-McDermid syndrome, a neurodevelopmental disorder that often leads to autism, also found no effects on parent-reported social behavior.

“The question of how we measure social behavior is one that the field is grappling with and that is still unsolved,” says Adam Guastella, professor of clinical psychology at the University of Sydney in Australia who was not involved in any of the studies .

Salience signal:

As researchers learned more about the role of oxytocin in the brain, ideas about how it affects social behavior have shifted, says Larry Young, director of the Translational Center for Neuroscience at Emory University in Atlanta, Georgia, who does not the new projects involved was studies. The hormone is now not supposed to improve sociability in general, but to make social stimuli more noticeable, he says, which helps people to better perceive things like facial expressions and body movements and to learn from them.

Given this new understanding, combining oxytocin treatment with some type of behavioral training could prove more effective in harnessing the hormone’s effects as a treatment, says Young.

And given the heterogeneity of autism, it’s possible that a subset of autistic people may still respond to oxytocin-based treatment, says Anagnostou. The children in the study could have had different forms of autism that affected their responses, but the study didn’t characterize the participants that way, she says.

More research is also needed to determine whether giving oxytocin intranasally is the most effective way to deliver the drug to the brain, the researchers say. On the one hand, it is unclear whether the hormone is absorbed by the brain in this form, says Guastella.

Even if it does, because of the way the body regulates hormone levels, it may be more effective to use a compound that activates oxytocin receptors, or even a parallel system in the brain, rather than oxytocin in the brain itself flood, Anagnostou adds.

It is important to consider whether “giving oxytocin is the best way to manipulate the system or should we consider other strategies,” she says.

Sikich says intranasal oxytocin treatment is unlikely to affect sociability, but she agrees that certain genetic subtypes – for example, people who are “particularly responsive to oxytocin” or [for whom] Oxytocin is completely gone ”- can still benefit.

For now, however, the study should give parents and clinicians a break if they are considering treating autistic children with off-label intranasal oxytocin, say several researchers.

“[The study] will dampen the enthusiasm accordingly, ”says Guastella.

Quote this article: https://doi.org/10.53053/JDDY3377


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