Gene illuminates the origins of depression

A new Yale study shines light on the genetic basis of depression.

In a study published in the scientific journal Nature Medicine, a team of Yale researchers led by psychiatry and pharmacology professor Ronald Duman found a gene that may control depression and lead to the development of more effective anti-depressants. The study, which examined post-mortem brain tissues and rodent behaviour, linked activation of the gene MKP-1, which inhibits an important neural signaling pathway, to the biological mechanism that drives depression.

“Depression used to be viewed as weakness not illness,” Duman said. “Understanding the biochemistry and molecular and cellular changes demonstrates this is a biological illness that has to be treated and taken care of.”

The study, which was funded by the U.S. Health Service and State of Connecticut, Connecticut Mental Health Center, examined post-mortem tissues from the hippocampal region of the human brain, an area that is responsible for long-term memory and spacial navigation. The researchers found that the MKP-1 gene was twice as active in depressed individuals as in non-depressed individuals.

“We chose to look at MKP-1 since it was the mostly highly abnormally regulated,” Duman said. “We felt that it was possible that this gene could be very important and a potential trigger to depression.”

Researchers found that the activation or deactivation of the gene determined how rodents would react to stress.

When researchers exposed rats to depression-inducing conditions, the activity of MKP-1 in the rats mirrored that in depressed humans, showing that depression univerally increases the expression of this gene, Vanja Duric, the first author of the paper, said. When the group ran a pre-clinical animal study to determine whether expression of the MKP-1 gene induced depressive behavior in rodents, they found that when the gene was activated rodents acted depressed when exposed to stress. When the gene was deleted, the mice were resistant to stress.

Researchers are now looking for a way to block this gene to provide an alternative way to combat depression.

“This study demonstrates that this gene could be the target for novel antidepressants,” Duman said.

Duric added that tests would have to be run to determine if drugs that deactivate this gene are effective antidepressants.

This kind of treatment, he said, would block the MKP-1 gene, using a different means than current medications.

“There is a significant limit and unmet need for treating depression,” Duman said. “Only one-third of patients respond the first antidepressant prescribed and only two-thirds of people respond to available medication.”

Researchers hope that such a drug would improve treatment of depression, which affects 16 perfect of Americans annually and produces an annual economic burden of $100 billion.

This research has particular importance for college students. According to the Depression Center at the University of Michigan, those within the ages of 15 and 24 years are the most susceptible to the onset of depression and other psychiatric disorders and as many as 15 percent of all college students have symptoms of depression.

The samples for the study were provided by the University of Mississippi.

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