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Why antidepressants don't work for so many
Date:10/23/2009

enes in the brain regions -- the hippocampus and amygdala -- commonly associated with depression in rats and humans.

Then she took four genetically different strains of rats and exposed them to chronic stress for two weeks. Afterwards, she identified the genes that had consistently increased or decreased in response to the stress in all four strains in the same brain regions.

Redei now had one set of depression-related genes that came out of an animal model of depression and one set of stress-related genes that came our of her chronic stress study.

Next she compared the two sets of genes to see if there were any similarities. "If the 'stress causes depression theory' was correct, there should have been a significant overlap between these two sets of genes," she said. "There weren't."

Out of a total of over 30,000 genes on the microarray, she discovered approximately 254 genes related to stress and 1275 genes related to depression, with an overlap of only five genes between the two.

"This overlap is insignificant, a very small percentage," Redei said. "This finding is clear evidence that at least in an animal model, chronic stress does not cause the same molecular changes as depression does."

Antidepressants Treat Stress Not Depression

Most animal models that are used by scientists to test antidepressants are based on the hypothesis that stress causes depression. "They stress the animals and look at their behavior," she said. "Then they manipulate the animals' behavior with drugs and say, 'OK, these are going to be good anti-depressants.' But they are not treating depression; they are treating stress."

That is one key reason why current antidepressants aren't doing a great job, Redei noted. She is now looking at the genes that differ in the depressed rat to narrow down targets for drug development.

She said another reason current antidepressants are often ineffective is that th
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Contact: Marla Paul
Marla-Paul@northwestern.edu
312-503-8928
Northwestern University
Source:Eurekalert

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