Obesity Leads to Depression via Social and Metabolic Factors

Megan Brooks

August 12, 2021

New research provides further evidence that a high body mass index (BMI) leads to depressed mood and poor well-being via social and physical factors.

Obesity and depression are "major global health challenges; our findings suggest that reducing obesity will lower depression and improve well-being," co–lead author Jessica O'Loughlin, PhD student, University of Exeter Medical School, Exeter, United Kingdom, told Medscape Medical News.

"Doctors should consider both the biological consequences of having a higher BMI as well as the social implications when treating patients with obesity in order to help reduce the odds of them developing depression," O'Loughlin added.

The study was published online July 16 in Human Molecular Genetics.

Large Body of Evidence

A large body of evidence indicates that higher BMI leads to depression.

O'Loughlin and colleagues leveraged genetic data from more than 145,000 individuals in the UK Biobank and Mendelian randomization to determine whether the causal link between high BMI and depression is the result of psychosocial pathways, physical pathways, or both.

The analysis showed that a genetically determined 1 standard deviation higher BMI (4.6 kg/m2) was associated with higher likelihood of depression (odds ratio [OR]: 1.50; 95% CI: 1.15 – 1.95) and lower well-being (β: -0.15; 95% CI: -0.26 to -0.04).

Using genetics to distinguish metabolic and psychosocial effects, the results also indicate that, even in the absence of adverse metabolic effects, "higher adiposity remains causal to depression and lowers wellbeing," the researchers report.

"We showed similar findings when looking at genetically predicted BMI and when using genetic variants that make you fatter but metabolically healthier (favorable adiposity genetic variants)," said O'Loughlin.

"Although we can't tell which factor plays a bigger role in the adiposity-depression relationship, our analysis suggests that both physical and social factors (eg, social stigma) play a role in the relationship between higher BMI and higher odds of depression," she added.

In contrast, there was little evidence that higher BMI in the presence or absence of adverse metabolic consequences causes generalized anxiety disorder.

"Finding ways to support people to lose weight could benefit their mental health as well as their physical health," co–lead author Francesco Casanova, PhD, with the University of Exeter Medical School, said in a statement.

Unexpected Finding

Reached for comment, Samoon Ahmad, MD, professor, Department of Psychiatry, New York University Grossman School of Medicine, New York City, said "multiple studies have shown a correlation between stress, obesity, inflammation, overall well-being, and psychiatric disorders, particularly depressive and anxiety disorders."

He said this new study is important for three reasons.

"The first is the cohort size. There were over 145,000 participants involved in the study, which is significant and serves to make its conclusions stronger," Ahmad noted.

"The second point is that the authors found that the correlation between higher adiposity and depression and lower well-being scores occurred even in patients without adverse metabolic effects," he told Medscape Medical News.

"Of note, obesity significantly increases the risk of developing type 2 diabetes, hypertension, and a host of other illnesses as well as inflammatory conditions, which can all have a negative impact on quality of life. Consequently, these can contribute to depression as well as anxiety," Ahmad added.

"Interestingly, what this study suggests is that even people without these additional stressors are reporting higher rates of depression and lower scores of well-being, while higher adiposity is the common denominator," he noted.

"Third, the paper found little to no correlation between higher adiposity and generalized anxiety disorder. This comes as a complete surprise because anxiety and depression are very common comorbidities," Ahmad said.

"Moreover, numerous studies as well as clinical data suggest that obesity leads to chronic inflammation, which in turn is associated with less favorable metabolic profiles, and that anxiety and depressive disorders may in some way be psychiatric manifestations of inflammation. To see one but not the other was quite an unexpected finding," Ahmad said.

The study was funded by the Academy of Medical Sciences. O'Loughlin, Casanova and Ahmad have disclosed no relevant conflicts of interest.

Hum Mol Genet. Published online July 16, 2021. Abstract

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