14 DAY TRIAL // Scientists have now found what the long lasting effects of depression are and why it is so hard to cure. They have found that depression triggers a biochemical change inside the brain producing a certain silencer molecule that inhibits the gene expression of a key protein.
In a previous article we have described the discovery of this key protein, p11. Its absence affects the receptors for the serotonin neurotransmitter and is responsible for generating the depression symptoms. The instructions for this p11, like all the other proteins, are encoded in the DNA.
It was thus speculated that depression may have genetic causes. Maybe the gene responsible for the p11 protein is defective. Now researchers, led by Eric Nestler, from the University of Texas Southwestern Medical Center, have found otherwise.
They have studied depressed mice. Mice exposed to aggression by a different dominant mouse daily for 10 days became socially defeated; they vigorously avoided other mice, even weeks later.
Scientists have found that depressed mice had a certain "silencer" molecule that prevented the expression of the p11 gene. They have also found that current anti-depressants do not target the silencer molecule - and thus the real cause of depression - but they activate a compensatory mechanism that, on the short run, outweighs the silencer. But the silencer still remains inside the brain like a biochemical scar and may have effects much later on.
"Our study provides insight into how chronic stress triggers changes in the brain that are much more long-lived than the effects of existing antidepressants," explained Nestler. "The molecular scar induced by chronic stress in the hippocampus, and perhaps elsewhere in the brain, can't be easily reversed. To really cure depression, we probably need to find new treatments that can remove the silencer molecules."
Nestler said social defeat stress probably has similarly effects on other genes as well.