Illustration of hybrid objects: part light bulb, part lab vial, some in blue and some in red to signify null and replicated results.
Illustration by Laurène Boglio

Null and Noteworthy: Arbaclofen results; another oxytocin edition

New data from clinical trials of arbaclofen and oxytocin underscore the murkiness of null results. Plus, researchers seek clarity on the neurodevelopmental effects of oxytocin during childbirth.

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Among the mass of data presented earlier this month at the International Society for Autism Research annual meeting was a significant null result: The drug arbaclofen, thought to balance excitatory and inhibitory brain signals, did not improve social skills in two separate trials of 5- to 17-year-olds with autism, although participants did show improvements on secondary measures, such as motor skills.

“We should conclude that we do not yet know whether arbaclofen is efficacious for social difficulties in children and adolescents with [autism],” Jeremy Veenstra-Vanderweele told Spectrum.

It can be difficult to parse the true meaning of a null result, an issue highlighted in last month’s Null and Noteworthy. This also applies to new oxytocin data, described below. If you have any null results to parse or wisdom to share, my inbox is open at [email protected].

Oxytocin as treatment:

The hormone oxytocin, thought to boost social behavior, has been tested over and over in autistic adults and children, with mixed results (several of which have been featured in this newsletter). A new study adds another null to the pile: Among 77 autistic children aged 8 to 12, those who took oxytocin intranasally for four weeks fared no better on social skills, as reported by parents, than did children receiving a placebo, though both groups improved significantly. The results were published in Molecular Autism in April.

But the picture is complex, says Larry Young, director of the Center for Translational Social Neuroscience at Emory University in Atlanta, Georgia, who was not involved in the work. Oxytocin temporarily boosts a person’s interest in social stimuli, he says, and so might work best as an augmenter of behavioral therapy, rather than as a stand-alone drug.

Indeed, in the trial described in the new study, the 10 children receiving oxytocin who also participated in a psychosocial therapy, such as emotion recognition training, for at least three sessions per month improved more than the 28 children with fewer than three sessions each month. “It’s a null result that is completely expected based on the properties of oxytocin,” Young says. “But it highlights the potential use of oxytocin when maybe it’s paired with some behavioral therapies.”

The results are far from proof that oxytocin can effectively boost engagement with such therapies, Young says. But they do suggest that the field should move away from trialing oxytocin in isolation: “It’s clear that just giving it like a vitamin is not going to work.”

Oxytocin in labor:

In a different context, oxytocin has been implicated in autism. The hormone is needed to start labor and is often used to induce or augment contractions, prompting studies of its effects on neurodevelopment. In a new study, researchers examined more than 414,000 births in British Columbia, Canada, where oxytocin is commonly used to both start and aid labor, as well as nearly 83,000 births in Israel, where in most cases clinicians use oxytocin only for the latter.

In crude analyses of both cohorts, any exposure to oxytocin during labor was associated with an increased chance of having a child with autism. In Canada, those links disappeared after adjusting for factors such as maternal health during pregnancy and the baby’s birth weight and gestational age. Among births in Israel, however, both oxytocin augmentation and non-oxytocin induction were associated with autism. The findings suggest that factors associated with labors that necessitate induction, and not the use of oxytocin itself, are linked with autism, the investigators write.

The findings were published in the American Journal of Obstetrics and Gynecology: Maternal-Fetal Medicine on 5 May.

Et al.:

  • Use of the epilepsy drug pregabalin during pregnancy does not increase a child’s chances of having autism, intellectual disability or birth complications such as low birth weight, according to a study of more than 3 million babies in Denmark, Finland, Norway and Sweden. Drug Safety
  • In a randomized trial of 29 autistic children with intellectual disability, tablet-based and flashcard-based augmented communication interventions improved communication skills equally well. An opinion piece for Spectrum previously covered the growing market of communication apps for autistic children. Journal of Applied Behavior Analysis