A Breakthrough Global Study of Depression Finds 44 Genetic Variants Linked to the Disease

Though depression affects an estimated 14 percent of the world’s population, scientists know very little about the underlying causes of the disorder, and that makes it incredibly difficult to treat. Even now, researchers are still debating whether common antidepressant medications even work at all, and if they do, why.

New research published in the journal Nature Genetics provides a big step in figuring out why some people suffer from depression while others don’t, identifying 44 genetic variants that are risk factors for major depression, 30 of which are new. They also found two regions of the brain that appear to be associated with the development of the disorder.

The study is the result of an international effort by more than 200 researchers involved with the Psychiatric Genomics Consortium. It looked at more than 135,000 cases of depression (both self-reported and clinically assessed) and almost 345,000 control cases. It’s the largest study on the genetic basis of depression ever done.

The researchers found that all humans carry some of the 44 risk factors identified. Some people carry more than others, putting them at greater risk for developing depression. They also identified the prefrontal and anterior cingulate cortices (both located at the front of the brain) as the regions of the brain probably linked with the development of depression.

Some of the risk factors the researchers identified are also involved in other psychiatric disorders, like schizophrenia, which isn't entirely surprising—a 2007 study from the Psychiatric Genomics Consortium found that people with depression, bipolar disorder, and schizophrenia as well as developmental disorders like ADHD and autism share the same variations in four locations in their genetic code.

By identifying genetic risk factors associated with major depressive disorder, the scientists hope to increase our understanding of why depression strikes some people and not others. "[M]ajor depression is a brain disorder," the researchers conclude. "Although this is not unexpected, some past models of [major depressive disorder] have had little or no place for heredity or biology." They firmly put to rest the idea that depression is entirely a matter of environment.

Environment certainly plays a role—the researchers found links between lower education levels and higher body mass index and depression risk as well—but genetics may impact whether someone whose circumstances put them at risk of depression actually develops the disorder. Depression is still highly stigmatized, which often prevents people from seeking treatment for it, according to several studies. Further understanding of the genetic underpinnings of the disorder may help counter negative perceptions of depression as a character flaw or a sign of laziness.

The study could eventually change how doctors treat depression. Many of the genetic variants identified by this study are linked to targets of current antidepressant medications, like serotonin. But the research may also lead to the development of new medications and therapies that could work for more people (current medications don't work for everyone) and potentially have fewer side effects than existing treatments.

The study partially relied on self-reported depression diagnoses, meaning there's some wiggle room in knowing whether those people are actually clinically depressed to the degree that a medical professional would diagnose. Further research will need to confirm that these genetic variants are indeed linked to depression. There are likely even more gene variants related to depression risk, as well, but they might have too small of an effect to be identified by this study. The researchers hope to continue their work to understand the links between environmental stressors, genetic variations, and depression risk in the future.