Yale researchers identify gene as possible cause for depression


Finding could prove target for future antidepressant

latimes.com

Sunday, October 17

Yale researchers have identified a gene as a possible culprit for depression and a possible target in the future for a new antidepressant.

A study published Sunday in the journal Nature identifies the gene MKP-1 as playing a significant role in depression. The study's lead author, Ronald Duman, professor of psychiatry and pharmacology at Yale, says that it could be a "primary cause" of the debilitating condition.

The research team arrived at their findings after conducting genome scans on tissue samples of 21 deceased people who had been diagnosed with depression. Comparing those to the genome scans of 18 people who did not have depression, the researchers saw that the presence of MKP-1 was more than twice as strong in the samples of those who had been diagnosed with depression.

"This one gene, MKP-1, was one of the most highly abnormal genes that we identified," Duman says.

These findings led to experiments on mice. In one experiment, they used gene transfer technology to give mice a greater expression of the gene —- equal to the levels found in the humans with depression. These mice then displayed typical depressive behavior seen in animals suffering from chronic stress —- for instance, failing to escape from its confines when given the opportunity. Another set of mice were bred with the MKP-1 gene deleted. These mice showed resilience to stress.

What the MKP-1 gene does, Duman says, is shut down a pathway in the brain necessary for neurons to function properly. The breakdown of the pathway has previously been shown to be a factor in depression. Duman was involved in a study earlier this year on the effects of the drug ketamine and its role in repairing damaged pathways.

Douglas Meineke, program chief at the National Institute of Mental Health, says the Yale study helps shed some light on the role that certain changes in the brain play in the development of depression.

"This paper contributes a new and potential target for therapies," Meineke says. "I would describe it as an important, small piece in a slowly emerging jigsaw puzzle."

Selective serotonin reuptake inhibitors (SSRIs, such as Prozac and Zoloft) are the most commonly prescribed antidepressants and work by regulating serotonin in the brain. However, up to 40 percent of patients don't respond to SSRIs. The exact cause of depression has been elusive; it's widely believed that multiple factors are at work.

The next step, Duman says, is to see if these findings can lead to a medication that can inhibit the MKP-1 gene. For research of this nature, screening for the drug's tests can take a few years. The actual development of the drug can take an additional several years.