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In a Stanford study of 30 children with autism, intranasal vasopressin improved social skills more than a placebo, suggesting that the hormone may treat core features of the disorder.

For release: May 1, 2019

From the

A pilot study led by聽Antonio Hardan, MD and , found that social behavior in children with聽autism improved after they inhaled a hormone called vasopressin.

Social behavior improved in children with autism after they inhaled a hormone called vasopressin, a pilot study by researchers at the has found. It is the first study to test intranasal vasopressin for any indication in children.

Although small, the placebo-controlled study of 30 children provides early evidence that vasopressin may reduce social impairments in the developmental disorder, which affects 1 in 59 U.S. children. The findings were published online May 1 in .

鈥淪ocial deficits are one of the core features of autism and a challenging area for many kids with the disorder,鈥� said the study鈥檚 lead author, , associate professor of psychiatry and behavioral sciences at Stanford. 鈥淪ome of these kids want to socially connect but aren鈥檛 capable of doing so.鈥�

The other core features of autism are poor verbal communication skills and restricted, repetitive behaviors. No existing medications address any core features of the disorder.

In the trial, parents鈥� and experts鈥� ratings of social behavior indicated more improvement in children treated with vasopressin than in those given a placebo. Vasopressin-treated children also experienced some reductions in anxiety and repetitive behaviors.

鈥淲e saw this across multiple measures independently,鈥� Parker said. 鈥淚t is really exciting.鈥�

鈥淲e might finally have an agent that will target these core features that are very hard to treat,鈥� said the study鈥檚 senior author, Antonio Hardan, MD, professor of psychiatry and behavioral sciences at Stanford. The researchers are now testing vasopressin in 100 additional children with autism to see if the pilot findings can be repeated.

鈥淏efore getting too excited, I want us to replicate this, and more importantly I want others to replicate our findings,鈥� added Hardan, who is also director of the聽Autism and Developmental Disabilities Clinic at Lucile Packard Children鈥檚 Hospital Stanford. Large trials are also needed to assure the drug鈥檚 safety.

Sex-specific social hormones

Vasopressin is a tiny protein hormone, nine amino acids long, manufactured in the hypothalamus. It differs by two amino acids from oxytocin, another hormone made in the same part of the brain.

Although both hormones play roles in social behavior, there are sex differences in their activity. Parker鈥檚 early research in animal models showed that, in males, vasopressin influences pair-bonding and fathering behavior. Oxytocin regulates aspects of childbirth and certain maternal behaviors, such as milk letdown during nursing.

Oxytocin has been tested as an autism treatment with mixed results; Parker and Hardan previously showed that among autistic children whose oxytocin levels were low to begin with, giving that hormone improved aspects of social behavior. However, many children with autism do not have low oxytocin levels.

Vasopressin鈥檚 social effects in males made the researchers wonder if this hormone influences autism. The disorder is male-biased, with 4 or 5 males affected for every female.

Parker and Hardan have previously shown that, compared with typically developing children, those with autism have lower vasopressin levels in their cerebrospinal fluid, which bathes the brain and spinal cord. Among children with autism, those with the lowest CSF vasopressin levels also have the lowest social functioning, the researchers have shown.

Dosing with vasopressin

The Stanford team recruited 30 children with autism, all of whom were 6 to 12 years old and had an IQ of at least 50. The participants were randomly assigned, in a double-blind fashion, to receive intranasal vasopressin or a placebo. Participants took daily doses of their assigned medication for four weeks.

At the beginning and end of the trial, several measurements were used to assess autism symptoms. Participants鈥� parents completed questionnaires rating their children鈥檚 social abilities. In the lab, the researchers tested participants鈥� ability to recognize emotional states in images of people鈥檚 eyes or facial expressions. Children鈥檚 repetitive behaviors and anxiety levels were also measured. The researchers also completed physical and clinical chemistry measurements to evaluate the safety of the treatment.

Children鈥檚 social abilities improved more after vasopressin than placebo, according to the parents鈥� and researchers鈥� observations, as did children鈥檚 performance on objective lab tests of social abilities. Vasopressin also reduced anxiety symptoms.

Identifying who responds and why is really important.

The changes in social ability and anxiety were greatest among children whose vasopressin levels were highest at the beginning of the study, a finding that surprised the researchers, given that their prior work had showed the lowest social abilities in children with the lowest vasopressin levels.

In addition, among children with the highest vasopressin at baseline, vasopressin treatment reduced restricted and repetitive behaviors. This finding did not extend to participants with lower baseline vasopressin.

The findings will guide larger trials of vasopressin. 鈥淚dentifying who responds and why is really important,鈥� Parker said. Because autism exists on a spectrum, with some people more severely affected than others, treatments must be individualized, she said.

If the findings of the pilot trial are replicated, it will also be important to validate the safety of the hormone in large populations and to understand which aspects of social behavior are most improved by vasopressin, Hardan added. 鈥淚s it motivation, affiliation, attachment? Ability to understand others鈥� mental states or read facial expressions or body language?鈥� he said. 鈥淭his has opened up a lot of possibilities for individuals with autism.鈥�

Other Stanford co-authors of the study are research scientist Ozge Oztan, PhD; clinical research coordinator Robin Libove; former life sciences researcher Noreen Mohsin; research scientist Debra Karhson, PhD; former assistant clinical research coordinator Raena Sumiyoshi; incoming medical resident Jacqueline Summers; Kyle Hinman, MD, clinical assistant professor of psychiatry and behavioral sciences; Kara Motonaga, MD, clinical associate professor of pediatrics; Jennifer Phillips, PhD, clinical associate professor of psychiatry and behavioral sciences; former postdoctoral scholar Dean Carson, PhD; Lawrence Fung, MD, PhD, clinical assistant professor of psychiatry and behavioral sciences; and Joseph Garner, DPhil, associate professor of comparative medicine.

Parker, Hardan, Fung and Garner are members of the . Parker, Hardan and Garner are also members of and the at Stanford. Garner is a faculty fellow of Stanford .

The research was supported by the (grants R21MH100387, R21HD083629, R01HD091972, K08MH111750 and T32MH019908), Autism Speaks, a Bass Society Pediatric Fellowship, the Mosbacher Family Fund for Autism Research, the Teresa and Charles Michael Endowed Fund for Autism Research and Education, the Stanford Maternal & Child Health Research Institute and the Yani Calmidis Memorial Fund for Autism Research.

厂迟补苍蹿辞谤诲鈥檚 also supported this work.

Media contact:

Erin Digitale
digitale@stanford.edu
(650) 724-9175