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Low Levels of Vasopressin Hormone in Cerebrospinal Fluid Possible Biomarker for Low Sociability Seen in Autism Spectrum Disorder

One of the characteristics of children with autism spectrum disorder is reduced social ability. It's difficult to study the possible causes of social impairment in children, but a new study shows that rhesus macaques with low sociability also had low levels of the peptide vasopressin in cerebrospinal fluid, as did children with autism spectrum disorder. The study, by researchers at the California National Primate Research Center (CNPRC) at the University of California (UC), Davis and Stanford University, was published online on May 2, 2018 in the journal Science Translational Medicine. The article is titled “Arginine Vasopressin in Cerebrospinal Fluid Is a Marker of Sociality in Nonhuman Primates.” "At this point, we consider vasopressin concentrations to be a biomarker for low sociability," said John Capitanio, PhD, Professor of Psychology at UC Davis and a research scientist at the CNPRC. Dr. Capitanio studies the interplay between social behavior and health. Over several years, his team has assessed rhesus macaque monkeys born at the Center for sociability. The Center maintains large field corrals where the macaques live in extended large family groups with the same hierarchies and social behavior that they show in the wild.nAbout fifteen percent of the animals are classed as "low social": they spend less time interacting with others than most macaques. Dr. Capitanio has previously studied how this natural variation affects the course of infectious disease. Professor Karen Parker at the Stanford Department of Psychiatry and Behavioral Sciences, principal investigator on the project, is interested in why children with autism spectrum disorder have deficits in social ability.

The researchers identified "high social" and "low social" monkeys and tested their blood and cerebrospinal fluid for a number of markers previously identified as possibly playing a role in autism. The one that jumped out was vasopressin in cerebrospinal fluid, which was low in "low social" animals. Other potential markers such as oxytocin were not significantly different, they found.

Dr. Parker’s and Dr. Capitanio's team was able to confirm the link between vasopressin and sociability in a second cohort of monkeys and demonstrate in a third group that vasopressin levels in cerebrospinal fluid are stable over time.

In addition, the Stanford team was able to obtain cerebrospinal fluid from seven children with autism spectrum disorder who were undergoing lumbar puncture for other reasons. They found that these children also had low levels of vasopressin compared to seven other children without autism.

There are some important limitations to the study, Dr. Capitanio said. Firstly, all the animals and children studied were male. Although autism spectrum disorder is far more common in males, research on females is also needed. Secondly, the study shows a correlation between sociability and vasopressin, but not whether it is a cause or a consequence.

Dr. Parker and Dr. Capitanio plan to repeat the study with female animals and to treat "low social" animals with vasopressin to see if that changes their behavior.

The monkey studies have particular relevance to humans because they are based on natural behavior, Dr. Capitanio said. "This is naturally occurring variation, we aren't making the monkeys behave in this way," he said.

Other authors on the paper are: Erna Tarara, Valentina Sclafani, Laura Del Rosso, and Katie Chun at UC Davis; Joseph Garner, Ozge Oztan, Sean Berquist, Antonio Hardan, and Sonia Partap at Stanford University; Elliott Sherr and Jiang Li at UC San Francisco; and Michael Chez at Sutter Neurosciences Medical Group, Sacramento.

IMAGE

Rhesus macaques live in large family groups, but a few animals consistently show less social interaction than others. New research at the California National Primate Research Center at UC Davis and Stanford University shows that these “low social” animals have low levels of the hormone vasopressin in cerebrospinal fluid. A similar result was seen in a small group of children with autism. (Credit: K. West, CNPRC).

[Press release] [Science Translational Medicine abstract]