The Role of Genetics in Depression

These new genetic discoveries may someday lead to new depression treatments.

 death thoughts, and more — you might ask yourself, "Why me?" Scientists are trying to answer that question.

Researchers know from twin and family studies that genetics does play a role in depression: You don’t actually inherit depression, but you may inherit genes that predispose you to the condition. If you have a parent or sibling with major depressive disorder, you are two to three times more likely to develop depression than someone with no family history. The risk is higher if family members developed depression early in life or experienced recurrent episodes of depression.

Risk Factors for Depression Vary

Having a genetic predisposition doesn’t mean you’ll become depressed. Environmental factors are also very important, says Mary Fristad, PhD, director of research and psychological services in the division of child and adolescent psychiatry at the Ohio State University in Columbus.

“Even if someone is ‘genetically loaded’ because they have multiple relatives with depression — and their partner is equally genetically loaded — raising a child in a calm, predictable, loving, nurturing, limit-setting household with good nutrition, plenty of exercise, adequate sleep, and participation in enjoyable activities might either prevent or delay the onset of depression,” she says.

Dr. Fristad doesn’t recommend genetic testing for depression. “The simplest and least expensive genetic test at present is to ask if anyone on either side of the family has depression,” she says.

But Chris Aiken, MD, director of the Mood Treatment Center and a clinical psychiatry instructor at the Wake Forest University School of Medicine, both in Winston-Salem, North Carolina, says one particular type of gene has been implicated in the development of depression — information that may be helpful to some people. It’s called the serotonin transporter (SERT); serotonin is a neurotransmitter that helps regulate levels of anxiety, depression, and irritability.

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“You can have genes for either a short or long version of SERT,” says Dr. Aiken. “These genes predict whether people will get depressed in the face of stress. For people with the long-arm version of the gene, the risk of depression doesn't rise even after a major life stress, like divorce, grief, or job loss. For those with the short-arm version, the rate of depression goes up with each new stress."

“What's interesting is that people have the same rate of depression when they aren't under any stress — regardless of which version of SERT they have,” Aiken says. “It's only after major stress or childhood trauma that the two groups start to look different.”

Having the long form of the gene raises the risk of experiencing depression after stress, but you won’t automatically become depressed if you have that gene and undergo stress. Similarly, you can still get depressed with the short-arm gene after a stressful life event (i.e., having the gene is not totally protective). In a nutshell, having a particular form of the gene raises the risk of depression after stress but cannot 100 percent predict or prevent it.

According to Aiken, the short-arm SERT isn’t unique to depression: It’s also been linked to post-traumatic stress disorder, fear responses, and alcoholism.

New Genetic Markers for Depression Revealed

In a study published in July 2015 in Nature, scientists reported finding two genetic markers that appear to be clearly linked to major depression. Researchers sequenced DNA from about 10,600 Chinese women, half of whom had depression. Of that half, 85 percent had a severe type of depression called melancholia, described as a gloomy, foreboding feeling that robs people of their joy. They found two genetic sequences that seemed to be linked to depression and confirmed these correlations in an additional 6,000 subjects and controls.

Norman Sussman, MD, a psychiatrist and director of the Treatment Resistant Depression Program at NYU Langone Medical Center in New York City says the results of this study help validate the fact that depression really is an illness, not a psychosomatic disorder or weakness of character.

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“I tell patients, depression is a medical disease," says Dr. Sussman. "Instead of [showing] physical symptoms (which they can also have), it primarily manifests through abnormalities in cognition and mood. You see things in a negative, hopeless way.”

The Nature findings also offer potential opportunity for treatment. Sussman says if we understand the mechanics of depression, it opens new pathways for drug development. Furthermore, says Aiken, knowing your genotype can also help you avoid wasting time with medications that are less likely to work. For example, people with short-arm SERT genes are less likely to respond to selective serotonin reuptake inhibitors, the most common type of antidepressant, but they may respond to other medications.

How You Can Prevent Depression Symptoms

There’s no medical test to diagnose depression, so health professionals rely on patients or family members to report symptoms. The American Psychiatric Association’s diagnostic guidelines say patients should not be diagnosed with depression unless they exhibit a persistently low mood or loss of interest in activities once deemed pleasurable or enjoyable, in addition to four or more symptoms of depression.

Depression symptoms might include loss of interest in activities once deemed pleasurable or enjoyable, significant weight loss or gain, lack of energy, feelings of worthlessness, or repeated thoughts of death or suicide.

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At least 10 percent of Americans will eventually experience an incidence of major depressive disorder, the most serious type of depression. Other people have low-grade, chronic depression. “The difference is severity,” says Sussman. “People with chronic depression know they should be happier than they are.” 

The important thing to keep in mind is that depression is not inevitable — even if you’re genetically predisposed — and it is treatable.

“Studies show that people whose environments are loving, nurturing, structured, physically active, and have good social networks and friendships are protective for children with genetic risks for depression,” says Aiken.

Online screening tools, such as the Depression Wellness Analyzer and the Patient Health Questionnaire (PHQ-9), can help you evaluate whether you may have depression. Discuss the results with your physician so you can seek treatment if appropriate.