Can Obesity Cause Depression?

A women walks down the street on Michigan Avenue 19 October, 2006 in Chicago, Illinois.

THE LINK BETWEEN BEING overweight and being depressed has long been known, but the reason for this link was poorly understood. Did the stigma of obesity increase depression risk? Did being depressed lead to the behaviors that cause weight gain? The link was always considered a correlation rather than a cause-and-effect relationship. Until now.

A recent study from the University of South Australia and University of Exeter in the U.K. has found strong evidence that obesity in fact causes depression, even without any other health problems. The research, published in the International Journal of Epidemiology, included data from more than 48,000 people with depression and a control group of more than 290,000 people born between 1938 and 1971.

Using medical history and genetic information, the researchers separated the psychological component of obesity from the impact of obesity-related health problems. They did this by focusing on genes associated with higher body mass index, but with lower risk of diseases like diabetes. “These genes were just as strongly associated with depression as those genes associated with higher BMI and diabetes. This suggests that being overweight causes depression both with and without related health issues – particularly in women,” the researchers said in a statement.

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“This study makes a good case that obesity can be a cause or contribute to the causes of depression,” says Dr. Jordan Smoller, a professor of psychiatry at Harvard Medical School and an expert in the genetic underpinnings of mental illness. “There are lots of studies suggesting an association between obesity and depression, but it’s hard to know whether obesity causes depression, depression causes obesity or if there is some other connection. This tells us that there may actually be a causal connection, for reasons we need to better understand,” says Smoller, director of psychiatric genetics for the Massachusetts General Hospital’s department of psychiatry, whose eponymous Smoller Laboratory works to understand the genetic basis of psychiatric disorders as part of the Psychiatric and Neurodevelopmental Genetics Unit.

Still More to Learn About the Link Between Obesity and Depression

How obesity causes depression is still unknown, says Laura Holsen, an assistant professor of psychiatry at Harvard Medical School and research associate in the departments of psychiatry and medicine at the Brigham and Women’s Hospital. “These results can’t prove why it happens, but it shines a flashlight” on areas to investigate, she says. “The mechanism might work through the brain, which makes sense. We know that the pathophysiology of both depression and obesity involves brain metabolism.”

Brain chemicals involved in both mood and weight gain often overlap, Smoller says. Hormones for weight metabolism and depression, including stress hormones, might be at play. These hormones, including cortisol, the so-called stress hormone, and leptin, which regulates body fat storage, “may be doing double duty,” he says.

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Another area of interest is inflammation, he says. “There is evidence that obesity and high-fat diets are related to the activation of inflammation pathways, and they are relevant to depression. Brain regions that regulate appetite overlap with regions that regulate mood.” Still another possibility is the role of the microbiome, the bacteria in the gut, which is also involved in weight regulation and mood.

Practical Implications for Patients and Doctors

What do these findings mean for patients and their doctors? “The study highlights the importance of considering this direct connection,” Holsen says. “This points to clinicians being more aware of early screening for changes in BMI. Along with the health effects of that on diabetes and cardiovascular risk, they should also be aware of the detrimental effects of higher BMI and mental health.”

Establishing a cause-and-effect link is important, says Dr. Drew Ramsey, assistant clinical professor of psychiatry at Columbia University and an expert on the relationship between diet and mental health. “It matters in the sense that, if obesity causes depression, then some types of depression are entirely preventable. It also matters in that it gives obese patients with depression more motivation, potentially, that losing weight may be great for their mental health.”

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Another even more recent study adds evidence that physical activity also has a genetic relationship to depression prevention. Researchers from the PNGU at Mass General published a report in JAMA Psychiatry this week. They used genetic data and found evidence that higher levels of physical activity may causally reduce risk for depression. Dietary changes and exercise go hand in hand in both weight and mood control.

“At the end of the day, we have lots of patients with obesity and with depression. This provides more education on how they are linked and how patients can find motivation in a challenging situation of being both obese and depressed,” Ramsey says. Studies like this help inform the search for what he calls “the holy grail” in psychiatry: Finding better biomarkers to categorize depression. “We understand there are different causes for clinical depression,” he says. “If we can find depression related to inflammation versus depression because of various genetic risks, that is the precision psychiatry we are trying to build.”