Genes that regulate the activity of a neurotransmitter in the brain are more abundant in depressed women than men, which could explain the higher incidence of suicide among women, researchers, including one of Indian-origin, have found.
Studying postmortem tissue from brains of psychiatric patients, Monsheel Sodhi, assistant professor of pharmacy practise at University of Illinois at Chicago in US, 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. Gender plays a role in depression and suicide, Sodhi said.
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 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 study, Sodhi and her coworkers analysed 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 committed 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.
The study was published in the journal Molecular Psychiatry.
