Gene Variants, Mutations Associated with Several Mental Disorders

Two recent studies have identified gene variants and mutations that significantly increased the likelihood of schizophrenia, alcoholism, and bipolar disorder development.

In a July 22 study published online in Nature, investigators observed the genome of 36,989 schizophrenia patients and 113,075 controls. The researchers highlighted 108 relevant loci, 83 of which had not been studied prior.

“By studying the genome, we are getting a better handle on the genetic variations that are making people vulnerable to psychiatric disease,” Thomas Insel, director of the National Institute of Mental Health, which institute helped fund the study, said in a statement. “Through the wonders of genomic technology, we are in a period in which, for the first time, we are beginning to understand many of the players at the molecular and cellular level.”

The investigators reported a notable association between the disorder and the region of the genome that holds DRD2, the target of all effective schizophrenia medications. Furthermore, the researchers found that the genes implicated were associated with malfunctioning in glutamatergic synaptic and calcium channel function.

Their findings supplemented previous research in Psychiatric Genetics conducted by University College London (UCL), which associated a variation in the metabolic glutamate receptor 3 gene (GRM3) with alcoholism, schizophrenia, and bipolar disorder. In the Nature study, GRM3 was the only gene out of 108 highlighted for which a specific mutation was associated with schizophrenia.

With the variant present in one of 200 individuals, the Psychiatric Genetics study found carriers of the GRM3 variant had a 3-fold risk of developing bipolar disorder, and the same mutation doubled to tripled the occurrence of schizophrenia or alcoholism, according to a UCL release.

Based on their findings, Andrew McQuillin, PhD, head of the UCL Molecular Psychiatry team for the previous study pointed out that other studies have attempted to treat schizophrenia by targeting glutamate receptors. However, treating patients with GRM3 mutations may produce more worthwhile results.

“Overall I expect we will see increased interest in drugs against both glutamate receptors and calcium channels as a result of the research,” he said in a statement.

Professor David Curtis of UCL’s Psychiatry Department, and a contributor of both studies claimed the results could help find the next big drug for treating mental illness.

“The work opens up new ways to prevent and treat mental illnesses by revealing the mechanisms involved in their development,” he said in a statement. “The result for GRM3 from the consortium is particularly compelling, as the odds of this occurring by chance are only one in a billion.”