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Hormone reduces social impairment in kids with autism | News Center

Hormone reduces social impairment in kids with autism | News Center

Social behavior improved in children with autism after they inhaled a hormone called vasopressin, a pilot study by researchers at the Stanford University School of Medicine 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 Science Translational Medicine.

“Social deficits are one of the core features of autism and a challenging area for many kids with the disorder,” said the study’s lead author, Karen Parker, PhD, associate professor of psychiatry and behavioral sciences at Stanford. “Some of these kids want to socially connect but aren’t capable of doing so.” 

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’ and experts’ ratings of social behavior improved more in children treated with vasopressin than in those given a placebo. Vasopressin-treated children also experienced some reductions in anxiety and repetitive behaviors.

“We saw this across multiple measures independently,” Parker said. “It is really exciting.”

“We might finally have an agent that will target these core features that are very hard to treat,” said the study’s 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. 

“Before getting too excited, I want us to replicate this, and more importantly I want others to replicate our findings,” added Hardan, who is also director of the Autism and Developmental Disabilities Clinic at Lucile Packard Children’s Hospital Stanford. Large trials are also needed to assure the drug’s 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’s 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’s 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’ parents completed questionnaires rating their children’s social abilities. In the lab, the researchers tested participants’ ability to recognize emotional states in images of people’s eyes or facial expressions. Children’s 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’s social abilities improved more after vasopressin than placebo, according to the parents’ and researchers’ observations, as did children’s 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. “Identifying who responds and why is really important,” 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. “Is it motivation, affiliation, attachment? Ability to understand others’ mental states or read facial expressions or body language?” he said. “This has opened up a lot of possibilities for individuals with autism.” 

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 Stanford Maternal & Child Health Research Institute. Parker, Hardan and Garner are also members of Stanford Bio-X and the Wu Tsai Neurosciences Institute at Stanford. Garner is a faculty fellow of Stanford ChEM-H.

The research was supported by the National Institutes of Health (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.

Stanford’s Department of Psychiatry and Behavioral Sciences also supported this work.

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