A recent study, published July 16 in Human Molecular Genetics, found that having a higher body mass index (BMI) increased the likelihood of depression, even in the absence of poor metabolic health and increased risk for weight-related diseases, including type 2 diabetes or heart disease. Obesity and depression have a bidirectional relationship — that is, having obesity does appear to cause depression, and depression does cause obesity, says Roger S. McIntyre, MD, a professor of psychiatry and pharmacology at the University of Toronto, who was not involved in the research. “This has been evaluated in both cross-sectional as well as longitudinal studies in both clinics and in the general population; it’s a robust and statistically significant association that goes in both directions,” says Dr. McIntyre. Obesity is a growing health crisis, both in the United States and around the world. According to the World Health Organization (WHO), worldwide obesity has nearly tripled since 1975; in the United States, it’s estimated that 39.6 percent of adults are considered obese, according to the most recent National Health and Nutrition Examination Survey (NHANES) data.

Researchers Examine Genetic Factors to Learn What Causes Depression in People With Obesity

Using data from a mental health questionnaire in 145,668 people with European ancestry in the U.K. Biobank, the study set out to determine if obesity related depression was made more likely do to due to health conditions associated with a higher BMI, such as heart disease, high blood pressure, or type 2 diabetes. The Biobank is a major international health resource, where over a half-million people ages 40 to 69 agreed to provide blood, urine, and saliva samples, as well as a detailed history for the purposes of research. This information allowed investigators to explore genetic causal factors using a method called Mendelian randomization, named after Gregor Mendel, the scientist who is considered the founder of the science of genetics. This method uses genetic variants to determine whether an observational association between a risk factor and an outcome is actually a cause and effect relationship, according to an article published in November 2017 the JAMA Guide to Statistics and Methods. Researchers used the genetic data from participants to look at two sets of previously discovered genetic variants. One set of the genes causes people to have more fat, yet better metabolic health, meaning that they were less likely to develop obesity-related diseases like hypertension and type 2 diabetes. The second set of genes made people heavier and metabolically unhealthy, making those individuals more prone to those conditions. Investigators found little difference in the rates of depression between the two groups, which suggests that even without adverse metabolic effects, having a higher BMI causes depression and lowers well-being. “This suggests that both physical health and social factors, such as social stigma, both play a role in the relationship between obesity and depression,” said lead author Jess O’Loughlin, a PhD student at the University of Exeter Medical School in England, in a release. “These findings align with what I see in clinic. When patients have obesity, a lot of their value and self-worth is determined by their weight status. This can start really early in life — as young as 3 years old,” says Fatima Cody Stanford, MD, MPH, assistant professor of medicine at Harvard Medical School and an obesity medicine doctor and researcher at Massachusetts General Hospital in Boston. Dr. Stanford was not involved in this research. “This depression is often present in patients who don’t have any of the metabolic issues that can be associated with having obesity,” she says.

Social and Environmental Factors May Contribute to Having Obesity

Depression and obesity are both multifactorial — there’s not just one cause for either condition, says McIntyre. “When one looks at how obesity causes depression, immediately what jumps out is social and environmental determinants. For example, if a person has insufficient access to healthy food due to economic insecurity, that would be a factor related to both obesity and depression,” he says. Childhood trauma in the form of abuse or neglect is another factor that predisposes someone to obesity, depression, or both, says McIntyre. Having obesity can also change the biology of the person with obesity, he explains. “For example, having obesity increases the likelihood of having insulin-resistance and prediabetes. There is actually evidence that shows that insulin resistance could lead to depression in some people,” says McIntyre. Inflammation may also contribute to mood disorders, he says. McIntyre explains, “Many people with obesity have an elevated state of inflammation, and that may impact the brain’s process in a way that puts a person at higher risk of depression.” This research highlights the complexity of the relationship between obesity and depression, he says. “Clearly there are factors influencing depression in people with obesity other than metabolic health. Further research is need to identify what those factors are,” says McIntyre.