Updated on 1/11/2022

By now, most of us know the major depressive symptoms well: Loss of pleasure in favorite activities, irritability, significant weight gain or loss, changes in sleeping habits, loss of energy, feeling worthless, an inability to think clearly, indecisiveness, hopelessness, and at its most severe, recurring thoughts of suicide.

The impact of depression is debilitating. The World Health Organization estimates that more than 300 million people globally suffer from depression — approximately 5 percent of the world’s population — and it’s the leading cause of disability. What’s worse, even in high-income countries nearly 50 percent of those with the illness don’t seek any form of depression treatment.

And while depression reaches the lives of so many worldwide and is arguably one of the most studied mental illnesses, we still know little about its origins. Is depression genetic? Is it environmental? Short answer: It’s complicated.

Depression and Genetics

There is a definite genetic link with depression. Most studies point toward depression as being 40 percent determined by genes.

“Twin and family studies give us the estimates and typically it’s a 40 percent heritability for general depression with somewhat higher heritability estimates for very severe forms,” Dr. Gerome Breen, of the Institute of Psychiatry, King’s College London tells Talkspace. “Sixty percent seems to be independent environment.”

In addition, research shows that those with a relative who experiences depression increases the risk that others in their family will also develop the illness.

“Someone with a family history of depression is at greater risk for developing major depression,” Director of Health Psychology, Cedars-Sinai Medical Center LA, Lekeisha A. Sumner, PhD, ABPP, tells Talkspace. “Individuals with a sibling or parent with major depression [have] approximately two to three times greater familial risk and the risk is even greater (with some estimates up to 5 times higher) if the relative had recurring depression and the onset of the depression was in early life.”

The (Lack of a) Depression Gene

As for the specific genetic markers that are definitively linked to depression, that’s a little trickier.

“Based on available data, it is not a single depressive gene that causes depression but is most likely a combination of genes that confers risk,” says Sumner.

A 2011 British study published in The American Journal of Psychiatry involving more than 800 families suggested that chromosome 3p25-26 is responsible for severe, recurrent depression in families. While this discovery marked a big breakthrough, this gene hasn’t been shown to predict less severe varieties of mental illness, meaning there are still likely several genes at play that have yet to be identified.

Serotonin, a kind of “feel good” neurotransmitter that has long been linked to depression, other types of mood disorders, anxiety, and obsessive-compulsive disorder, may be another piece of the genetic puzzle.

“An imbalance of serotonin is believed to interrupt the relay of messages to the brain whose impact is not exclusive to mood, but also to an individual’s psychological functions including activities of daily living, including sleep, appetite and sometimes behavior.”

Talkspace therapist Elizabeth Keohan, LCSW-C, MSW

Chris Aiken, MD, director of the Mood Treatment Center and a clinical psychiatry instructor at the Wake Forest University, explained to Everyday Health that a gene called the serotonin transporter (SERT) has also been linked with depression, particularly in how genetic variations interact with stress.

“You can have genes for either a short or long version of SERT,” Aiken explains. “These genes predict whether people will get depressed in the face of stress. For people with the long-arm gene variant, 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 gene variant, the rate of depression goes up with each new stress.”

Even this isn’t conclusive, as Aiken relays that “people have the same rate of depression when they aren’t under any stress — regardless of which version of SERT they have. It’s only after major stress or childhood trauma that the two groups start to look different.”

Depression and the Environment

All this to say that even people who come from families with a history of depression are not guaranteed to experience depressive episodes in their life.

“Family history does not necessarily dictate that someone will develop major depression, although they are at increased risk,” says Sumner. Or as Dr. Robert Klitzman, a professor of clinical psychiatry and director of the master’s program in bioethics at Columbia University, tells The New York Times. “Doctors see [genetic tests] much more like predicting the weather.”

To predict depression, despite a strong genetic correlation, there’s still that 60 percent risk that is directly related to one’s environment.

“Genetic risk is only a part of the equation,” says Sumner. “Psychosocial stress and one’s interaction with their environment are important.”

“Adverse experiences can be a major component of depression. Relationships or employment, for example, can reveal how individuals are negatively connected to sometimes toxic and impactful situations that can be a driving force for stress and depressed mood.”

Talkspace therapist Elizabeth Keohan, LCSW-C, MSW

Environmental factors Sumner identifies that can lead to depression include “a household where the caregivers were severely depressed,” “severe life stress, chronic strain, a history of abuse or neglect, [and] maladaptive coping, among other factors.” Add to the list trauma, loss of a loved one, social isolation, serious physical illness, and other major life events.

Genetics and the Environment

Here’s where the plot thickens. Researchers also believe that the environment can have an impact on genes themselves, meaning it’s almost impossible to untangle genetics from environmental factors.

“The 40 percent estimate [of heritability] is best thought of as the combined effects of genetics and the environment that interacts with those genetics,” says Breen. ”Our genome is an underlying risk. In order for that risk to become active, you need some environmental triggers.”

While the environmental triggers can be the factors discussed above, it can be more complicated than that. Researchers are also looking at what’s called epigenetics, which Dr. Michael J. Meaney of Hope Through Research describes it as “the study of how external or environmental factors can switch genes on and off without actually changing the structure of the genes in a given DNA sequence.”

To understand how complex this research is, take for example that some of Breen’s colleagues have discovered that not only can parents influence their children’s mental health, but it may also work the other way around.

“At least some of the time, it appears that if a child has anxiety or depression that the parents then develop anxiety or depression because of that,” Breen says. “In a cross section review, if you just look at that family in one point of time, you might think depression is genetic or environmental — it’s been passed from the parents to the children. But based on an analysis using a type of twin design…the transmission goes in both ways, from the kids back to the parents as well.”

Bottom line, there’s still a lot that scientists are working to discover about how depression works, and it’s more than just genetics or the environment as individual risk factors. Looking at the full picture holistically is where experts such as Breen are hoping research goes in the future.

What This Means for the Future of Treatment

Studying genetics and the environment together will only improve our understanding of depression, better predict risk factors, and help us more effectively treat the illness.

“The development of new treatments for depression has been relatively slow,” Breen tells us. “People have been measuring depression and genetics. Or they’ve been measuring depression and environment, but they haven’t been putting all three things together in one study.It may be that by combining genetic data with environmental data, we can speed that up.”

“The genetics of depression are complex,” adds Sumner. “Allowing greater precision in identification in risk and estimates of risk allows improved screening.”

With increased study and a better understanding of the genetic, environmental, and genetic-environment correlations, there’s hope that in the future we’ll have even better tools for treating one of the world’s most debilitating mental illnesses.