Gene Network Involved in Autism, ADHD, Schizophrenia

By Traci Pedersen
October 1st, 2022
Medically reviewed by Paul Sietes, MD.

Researchers have discovered several gene networks involved in autism. One was also found to affect some patients with attention-deficit hyperactivity disorder (ADHD) and schizophrenia — raising the possibility that all three neurological disorders could be treated in a similar way.

“Neurodevelopmental disorders are extremely heterogeneous, both clinically and genetically,” said study leader Hakon Hakonarson, M.D., Ph.D., director of the Center for Applied Genomics at The Children’s Hospital of Philadelphia (CHOP).

“However, the common biological patterns we are finding across disease categories strongly imply that focusing on underlying molecular defects may bring us closer to devising therapies.”

Research findings, based on a large analysis of DNA from thousands of patients, may one day provide new targets for autism drugs.

The study, published in  Nature Communications, pulls from gene data from CHOP’s genome center as well as from the Autism Genome Project and the AGRE Consortium, both part of the organization Autism Speaks.

The research is a genome-wide association study comparing more than 6,700 patients with autism spectrum disorders (ASDs) to over 12,500 control subjects. It was one of the largest studies of copy number variations (CNVs) in autism ever conducted. CNVs are deletions or duplications of DNA sequences.

The researchers previously reported that 10 percent or more of ADHD patients have CNVs in genes along the glutamate receptor metabotropic (GRM) pathway, while other studies have found GRM gene defects in schizophrenia as well.

Based on their findings, Hakonarson is planning a clinical trial in selected ADHD patients of a drug that activates the GRM pathway.

“If drugs affecting this pathway prove successful in this subset of patients with ADHD, we may then test these drugs in autism patients with similar gene variants,” he said.

In ASDs and other complex neurodevelopmental disorders, common gene variants often have very small individual effects, while very rare gene variants have stronger effects.

“Even though our own study was large, it captures only about 20 percent of genes causing ASDs,” said Hakonarson, who added that still larger studies are needed to further investigate the genetic underpinnings of autism.

“However, strong animal data support an important role for the glutamate receptor pathway in socially impaired behaviors modeling ASDs. Because the GRM pathway seems to be a major driver in three diseases —  autism, ADHD, and schizophrenia —  there is a compelling rationale for investigating treatment strategies focused on this pathway.”

Source: Children’s Hospital of Philadelphia

Traci Pedersen is a professional writer with over a decade of experience. Her work consists of writing for both print and online publishers in a variety of genres including science chapter books, college and career articles, and elementary school curriculum.