In Monkeys, Researchers Find Possible Biological Marker of Autism

Researchers have been left empty-handed so far in their quest to uncover some measurable biological signal that could be used to diagnose autism spectrum disorder, leaving clinicians to identify the condition just based on a child’s behavior.

But on Wednesday, scientists reported in the journal Science Translational Medicine that a hormone that regulates blood pressure could be one of those signposts.

They found that low concentrations of the molecule — called arginine vasopressin, or AVP — in the cerebrospinal fluid corresponded to autism-like social behavior in male monkeys, while a high AVP concentration signaled the most social animals. And they discovered similar results when looking at AVP concentrations in the cerebrospinal fluid, or CSF, of a small group of boys.

“It’s really exciting work,” said Dr. Mollie Meffert, a molecular neuroscientist at Johns Hopkins, who was not involved in the study. “One of the most interesting things is the finding that the vasopressin in the CSF correlates with sociality in the macaques and in autism with children.”

Meffert said if vasopressin concentrations are confirmed to correspond to autism, they could perhaps be used to diagnose the condition and as a gauge to measure the effect of treatment candidates. And Karen Parker, the lead author of the study and associate professor of psychiatry and behavioral sciences at Stanford, said that the hormone could become a drug target if future studies show boosting its levels can assuage the social impairments of autism spectrum disorder.

Autism is diagnosed based on social and communication deficits and repetitive behaviors like hand-flapping or obsessions.

A biological diagnostic test for autism is so important, researchers say, because the earlier children start therapeutic interventions, the better the results. Without a medical test, children are typically diagnosed around age 4 1/2, based on their behavior or a lag in their development.

Parker emphasized that the study’s findings are preliminary, and that the discovery of low AVP concentrations in boys with autism was based on so few samples that it needs to be replicated in a larger study. Future studies will also explore whether that association holds in adults and if levels of AVP or other hormones are associated with autism in girls and female animals.

Parker added that parents should not try to treat their children with vasopressin, which is used to regulate blood pressure and to treat a condition called diabetes insipidus, given that it has not been tested in autism, it’s not clear what the appropriate dose would be, and it can have significant side effects.

One challenge in studying the underlying biology of autism spectrum disorder is the lack of reliable rodent models of the condition. But Parker and colleagues have in past studies established that the natural variation of social functioning in monkeys can serve as a solid stand-in for people.

“They have the complex social cognition that we would care about for the control individuals, and if we can identify animals that have a deficit that’s spontaneously occurring — like humans do — that’s the value of the model,” said Parker, who is also an affiliate scientist at the California National Primate Research Center.

For the new study, the researchers identified 15 male rhesus macaques that exhibited low sociality, meaning they weren’t interested in playing with or grooming their fellow macaques, along with 15 highly social monkeys. They then ran tests looking for any significant differences in nine biological markers that had been implicated in past studies as possibly linked to autism, including the expression of certain genes, the products of certain signaling pathways, and the concentrations of the hormones AVP and oxytocin.

Only one stood out as a marker for the differences in social behavior: the concentration of AVP in the monkey’s cerebrospinal fluid, a colorless material that coats the brain and spinal cord. Notably, the levels of AVP in the blood showed no significant divergence in the two groups of monkeys.

To confirm their results, the researchers looked at a second group of male monkeys and again homed in on AVP concentration in the cerebrospinal fluid as being correlated to the sociality of the monkey — the lower the AVP, the less they interacted with their fellow macaques.

Then it was time to look at people.

Because obtaining cerebrospinal fluid is invasive — it requires a lumbar tap — the researchers relied on samples that had been previously collected from boys for other medical reasons, often as part of a chemotherapy treatment. They found that boys with autism spectrum disorder had lower AVP concentrations in their CSF, though with only 14 samples total — seven from control boys and seven from boys with autism spectrum disorder — the researchers could not draw firm conclusions.

Parker said that it’s not clear if low AVP concentrations in the cerebrospinal fluid might contribute to the social problems of autism or just be another consequence of the condition. She also added that it would likely just be one biological marker of autism, which has complicated, multifaceted causes.

But she said researchers have for several decades viewed vasopressin as an key influencer of social function, particularly in male animals. If AVP does indeed have some role to play in autism spectrum disorder, then its importance in males could help explain in part why three to four times more males are diagnosed with the condition than females.

“When people talk about autism, one of the things that feels a bit neglected is that the prevalence is very male-biased,” Parker said. “So if you’re thinking about disease mechanisms, it would be really interesting to think about the biology that’s informative to either male or female functioning.”