While previous studies have found that people who are obese are more likely to have depression, it has been unclear whether that is down to depression driving weight changes or the reverse.

Now, in the largest study of its kind, experts say having genetic variants linked to a high body mass index (BMI) can lead to depression, with a stronger effect in women than men. What’s more, they say the research suggests the effect could be down to factors such as body image.

“People who are more overweight in a population are more depressed, and that is likely to be at least partly [a] causal effect of BMI [on] depression,” said Prof Tim Frayling, a co-author of the study, from the University of Exeter medical school.

Writing in the International Journal of Epidemiology, the researchers from the UK and Australia describe how they used data from the UK Biobank, a research endeavour involving 500,000 participants aged between 37 and 73 who were recruited in 2006-10.

The researchers looked at 73 genetic variants linked to a high BMI that are also associated with a higher risk of diseases such diabetes and heart disease. They also looked at 14 genetic variants linked to a high percentage of body fat but which were associated with a lower risk of such health problems.

The team then looked at participants’ hospital data and answers from a host of questionnaires – including self-reports of seeing a GP or psychiatrist for anxiety or depression. The team identified about 49,000 participants whom they were confident had depression.

Overall, the team found that people with a higher BMI were more likely to be depressed.

The researchers also found that being genetically predisposed to a higher BMI was linked to depression, with the effect stronger in women than in men. The results held even when they carried out additional tests, such as excluding individuals with a family history of depression, and when the analysis was repeated on data from a large international project called the Psychiatric Genomics Consortium.

Focusing on the 73 genetic variants, and taking into account factors including age and sex, they found that for every 4.7-point increase in BMI, the odds of being depressed increased by 18% overall, and by 23% among women.

When the team pooled data from the different sources, they found the 14 genetic variants that increase body fat but are not linked to metabolic ill-health were also linked to an increased chance of having depression.

“It suggests the psychological component is just as strong as any physiological component, if [the latter] is there at all,” Frayling said, suggesting poor body image could be one mechanism at play.

The study has some limitations: it primarily looked at individuals with white European ancestry, and involved some self-reported data.

While the study does not show that weight gain for other reasons would increase the risk of depression, Frayling said it was likely. “It allows [one] to infer that bigger effects in BMI would have bigger effects on depression,” he said.

Naveed Sattar, a professor of metabolic medicine at the University of Glasgow, welcomed the research. “These new findings are perhaps the strongest so far to suggest higher weights may actually contribute to depression,” he said. “Of course, many other factors can cause depression, but, even so, weight loss might be helpful to improve mental health in some individuals, whereas keeping leaner in general should help lessen chances of depression.”

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