One Gene Overrides Another To Prevent Brain Changes That Foster Depression

For what appears to be the first time in humans, scientists have detected an interaction between genes that may help prevent brain changes that increase vulnerability to depression.

A variation on one gene affects how much of the brain chemical serotonin is available to brain cells. This variation is thought to raise the risk of depression in people who carry it. But NIMH scientists found that a variation in another gene, which produces brain-derived neurotrophic factor (BDNF) - a substance that enables growth and health of brain cells - appears to prevent or offset the changes generated by the depression-fostering variant.

For now, the finding can help scientists track the biological roots of depression in the brain as they search for better treatments. In the future, it could help clinicians identify patients who are at risk and need monitoring or treatment.

Results of the study were published online on March 12, in Molecular Psychiatry, by Lukas Pezawas, Daniel R. Weinberger, and colleagues from the National Institute of Mental Health, the Universities of Pittsburgh and Vienna, and Germany's Central Institute of Mental Health.

Using brain imaging in a study of 111 healthy people, the researchers found that those with the depression-promoting gene variation had alterations in brain-cell networks known to regulate mood. But those who had both the depression-promoting variation and the apparently protective variation did not have these alterations in brain-cell networks.

Not everyone who has the serotonin-related variation develops depression, a disorder thought to be caused by interactions between variations in many genes and life experiences, such as stressful events. One variation in a single gene does not appear to cause the disorder.

In this study, the scientists examined healthy people, rather than depressed people, because the illness might have introduced factors that would have confused the results. The study was not meant to show whether people became depressed, but rather to show whether the gene variations resulted in brain changes that set the stage for depression, or protection from it, in the mood-regulating brain-cell networks.

Further research may tell if the different variations actually translate into differences in rates of depression among their carriers.