The biology of depression

Nils Werner

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For years, doctors have known that depression, the most common mental illness, is triggered by a genetic vulnerability, stressful life events, or both. As an old medical adage goes: “Genes load the gun. The environment pulls the trigger.”

Now, a study that gleaned genetic information from 1.2 million volunteers has spotlighted 178 variations tied to depression. The findings, by Veterans Affairs–affiliated researchers at Yale and University of California–San Diego, shed a glimmer of light on the biological basis of this common illness. They may also lead to new ways for designing effective treatments. “We’ve more than doubled the number of genetic variations associated with depression, so in a way it’s a great leap forward,” says Daniel Levey, assistant professor of psychiatry.

For the study, published in Nature Neuroscience, researchers retrieved information from four banks: the VA’s Million Veteran Program, the UK Biobank, FinnGen (based in Finland), and 23andMe. They also used study results from the Psychiatric Genomics Consortium, a global collaboration that pools and analyzes data on the genetics of mental illness. For confirmation, they compared their findings with data from an additional 1.3 million volunteers/customers of 23andMe. “The study was much larger than previous studies and confirmed a lot of what we had seen, and also identified novel loci that hadn’t been seen to be statistically significant,” says Joel Gelernter ’79, the Foundations Fund Professor of Psychiatry.

Gelernter says the insights gained have helped scientists identify genetic pathways of depression that overlap with other diseases. With this information, researchers can test the drugs used for those other ailments to find out if they also work for depression.

The word “depression” likely covers many different diseases. Studying the genes may one day give scientists a more accurate picture of individual ailments. “If you understand the biology better,” says Gelernter, “then you understand better how to treat what goes wrong.”