Researchers from Columbia and Vanderbilt universities, the University of Illinois Chicago and colleagues across the country are making steady progress in their decades-long quest to understand autism spectrum disorder (ASD), a brain development condition that affects social interaction, communication and behavior.
A target of their investigations is serotonin, a signaling molecule that is well known for its critical roles in regulating mood and which also plays an important role in the development of the brain and nervous system.
In a recent study, the researchers measured blood levels of serotonin in women whose children were diagnosed with ASD. Some of the children carried rare genetic variations that strongly contribute to the risk of autism, while others did not.
In their paper, published July 4 in the Journal of Clinical Investigation, the researchers reported that higher serotonin levels were primarily found in women whose children who did not carry the rare variants.
This finding suggests that elevated maternal serotonin levels are associated with autism in a subset of children who have multiple common genetic or environmental factors which likely contribute to risk. Elevated levels are not found as frequently when a single, rare genetic variant explains most of the risk.
The link between autism-associated genetic variations and maternal serotonin levels was first described more than 60 years ago.
But it is a complicated picture that is not fully understood, noted James Sutcliffe, PhD, a pioneer in autism genetics at Vanderbilt University.
The study probed genetic samples from the University of Illinois Chicago (UIC) Autism Center of Excellence and from the UIC and Vanderbilt sites of the Simons Simplex Collection, a repository of samples from 2,600 families of children with ASD maintained by the Simons Foundation Autism Research Initiative.
The study did not have a control group — it did not compare maternal serotonin levels to those from women whose children do not have autism. Another limitation was that serotonin blood levels in the women were measured after their children had been diagnosed with ASD.
Taking measurements throughout pregnancy would provide a more complete picture of how maternal serotonin levels may relate to autism risk, said Jeremy Veenstra-VanderWeele, MD, the Ruane Professor of Psychiatry and director of the Division of Child & Adolescent Psychiatry at Columbia University Irving Medical Center in New York City.
Veenstra-VanderWeele is corresponding author of the paper. Before coming to Columbia in 2014, he directed the Division of Child and Adolescent Psychiatry at Vanderbilt University Medical Center and was medical director of the Treatment and Research Institute for Autism Spectrum Disorders (TRIAD) at the Vanderbilt Kennedy Center.
Sutcliffe, who co-authored the paper, is associate professor of Molecular Physiology & Biophysics and of Psychiatry & Behavioral Sciences at Vanderbilt.
Other co-authors are Edwin Cook, MD, also a pioneer in autism genetics who directs the Center for Neurodevelopmental Disorders and the Division of Child and Adolescent Psychiatry at UI Health, and colleagues from New York University and Yale University School of Medicine.
While the true nature of the relationship between serotonin levels and ASD remains elusive, clinical trials are underway at Vanderbilt and elsewhere to evaluate drugs that, by impacting the serotonin system, may relieve irritability or improve social functioning in children with autism.
Genetic studies also have led to the identification of other, possibly related health conditions in children with ASD, including previously undiagnosed cardiac abnormalities and severe epilepsy that occurs during sleep, Sutcliffe said.
The investigators hope that further research may lead to targeted interventions based upon ASD-associated genetic variation or biomarkers. That, Veenstra-Vanderweele said, would be “transformative” for children who are severely affected by autism.
