Overactive Glutamate Receptor Gene Tied to Depression in Women

A new study has found depressed women have an abnormally high expression of the genes that regulate the glutamate system.

Glutamate is the major excitatory neurotransmitter in the brain, according to a researcher at the University of Illinois at Chicago. Schizophrenia, epilepsy, autism and Alzheimer’s disease have all been linked to abnormalities of the glutamate system.

This overabundance may be an underlying cause of the higher incidence of suicide among women, said Monsheel Sodhi, Ph.D., an assistant professor of pharmacy practice at the university.

Gender plays a role in depression and suicide, according to Sodhi. While women are two to three times more likely to attempt suicide, men are four times more likely to die by suicide.

Sodhi noted she and her colleagues were intrigued by recent studies that found that a low dose of the drug ketamine, which alters glutamate system activity, can rapidly eliminate depression in two-thirds of patients who do not respond to conventional antidepressants. Conventional antidepressants target the monoamine systems, which secrete the neurotransmitters dopamine, serotonin or norepinephrine.

In the new study, published in the journal Molecular Psychiatry, Sodhi and her research team analyzed post-mortem brain tissue from people who had suffered from depression. Both females and males were compared to subjects who had never experienced psychiatric illness. Many of the depressed patients, she said, died by suicide.

Females with depression had the highest levels of expression of several glutamate receptor genes, perhaps making them more prone to depression, according to the study’s findings. In addition, three of these genes were found to be elevated in both male and female patients who had died by suicide, Sodhi noted.

“Our data indicate that females with major depression who are at high risk of suicide may have the greatest antidepressant benefit from drugs that act on the glutamate system, such as ketamine,” Sodhi said.

Source: University of Illinois at Chicago

Woman with depression photo by shutterstock.