By Elizabeth Lopatto - 2012-06-25T19:00:00Z

Chronic stress appears to block a gene that guards against brain atrophy associated with depression, according to a study in rats that may help guide new treatments for mood disorders.

The gene, called neuritin, appears to be responsible for keeping healthy neuron connections in certain parts of the brain, according to the study published in the Proceedings of the National Academy of Sciences. Rats whose genes were suppressed were more anxious and depressed than those whose genes werent, an experiment found. Further, activating the gene led to an antidepressant response.

The research adds evidence to the idea that depression may be caused by atrophy in the hippocampus, the part of the brain responsible for mood and memory. Scientists have previously shown that some antidepressants increase the growth of new connections, called synapses, between neurons.

This is based on findings that basically stress and depression have been shown to cause atrophy, said Ronald Duman, a study author and professor of psychiatry at Yale University in New Haven, Connecticut, in a telephone interview. Theres good evidence theres a loss of synaptic connections in depressed rodents and depressed patients. If you dont have the appropriate number of connections in synapses, your brain isnt going to function properly.

Researchers found that chronically stressed rats, those who had been deprived of food, forced to swim in cold water, exposed to frightening odors and other stressors, had lower levels of neuritin expression and exhibited depressed behavior. The researchers then dosed the stressed rats with neuritin-boosting therapy, which improved the animals ability to swim longer without giving up in a test.

In another experiment reported in the study, rats were dosed with gene therapy to boost neuritins availability in the brain. That led to new neuron growth. Researchers also used gene therapy to suppress neuritin. These animals were less likely to eat right away and were more likely to show despairing behaviors when they were subjected to stress.

An estimated 9 percent of American adults are depressed, according to the U.S. Centers for Disease Control and Prevention. Discovering new drugs to treat people who are depressed may decrease disability and suicide rates, according to background information in the paper.

Its not clear exactly how current antidepressants including selective serotonin reuptake inhibitors, or SSRIs, like Eli Lilly & Co. (LLY)s Prozac, work in the brain. SSRIs are designed to block the reabsorption of the brain chemical serotonin. Still, previous work attempting to show serotonin is solely responsible for depression has been unsuccessful. The alternative theory about the role of neurogenesis developed in response.

Todays study shows a causal link between neuritin and depression, at least in rats, Duman said. Human studies will be more complicated, in part because there isnt a known drug that acts directly on neuritin in humans.

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Stress Blocks Gene That Guards Brain Against Depression

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