A new study conducted at the University of Illinois at Chicago may have found the underlying cause of the higher incidence of attempted suicide in women.
Researchers found an abundance of numerous genes that regulate the activity of a neurotransmitter in the brain in the brain tissue of depressed females.
Studying postmortem tissue from brains of psychiatric patients, Monsheel Sodhi, assistant professor of pharmacy practice at UIC, noted that female patients with depression had abnormally high expression levels of many genes that regulate the glutamate system, which is widely distributed in the brain.
Glutamate is the major excitatory neurotransmitter in the brain. Schizophrenia, epilepsy, autism and Alzheimer’s disease have all been linked to abnormalities of the glutamate system.
Sodhi said that women are two to three times more likely to attempt suicide, but men are four times more likely to die by suicide. The risk of suicide is associated with changes in several neurotransmitter systems.
Sodhi and her team of researchers 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 coworkers analyzed 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, had died by suicide. Females with depression, Sodhi discovered, had the highest levels of expression of several glutamate receptor genes, perhaps making them more prone to depression. In addition, three of these genes were found to be elevated in both male and female patients who had died by suicide.
“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. The study also suggests new glutamate receptor targets for development of treatments for depression and identifies biochemical markers that could be used to assess suicide risk, she said.
Only one-third of patients receiving conventional treatments achieve substantial remission of their depression, which may take several weeks or longer, Sodhi said. This time lag in response to treatment is a problem, she said, due to the high risk of suicide.