Journal of Psychiatry & Neuroscience : JPN | 2021
Can treatment of obesity reduce depression or vice versa?
Abstract
Both obesity and depression are widespread problems with major health and socioeconomic implications. The number of individuals who are overweight or obese has increased dramatically over the last 25 years. Globally, 39% of adults aged 18 and older were overweight and 13% obese,1 and more than 264 million people of all ages suffer from depression.2 Both illnesses are risk factors for a number of chronic diseases, including cardiovascular disease,3,4 and a bidirectional link between risk of depression and obesity in individuals has been proposed.5–7 Given that obesity is on the rise in many countries, an increasingly large proportion of the popu lation is at risk for depression. Vulnerability to depression among people with obesity suggests that there may be mechanistic links underlying these disorders, although the biological mechanisms remain poorly understood. This editor ial discusses the evidence for the link between obesity and depression and the neurobiological mechanisms that may underlie this vulnerability (Figure 1). This has the potential to inform clinical evaluation and identify research questions in this area to help further define treatments. Epidemiological and observational studies assessing an association between obesity and depression have reported mixed findings. Some studies purport a positive association,8–11 whereas others indicate no association12 or a U-shaped association whereby both underweight and obesity are associated with depression.6 A meta-analysis examining longitudinal studies determined that individuals with obesity were 55% more likely to become depressed, and individuals with depression were 58% more likely to become obese.5 Notably, associations between higher body mass index (BMI) and higher odds of depression are stronger in women than men, with a U-shaped association in men.6,13 Thus, obesity increases the risk of depression and, conversely, depressive disorders are predictive of developing obesity.7 While these studies identify the relative odds of co-occurrence of these disorders, determining if BMI causally influences depression is challenging without a mechanistic understanding of the vulnerabilities. People with depression and/or anxiety commonly experience a symptom profile that influences appetite, energy and motivation. As a result, presentation of major depressive disorder (MDD) is often consistent with a phenotype that increases vulnerability toward weight gain.14 Individuals with atypical depression may be particularly prone to obesity, as this subtype of MDD is characterized by overeating, oversleeping and fatigue.15 This can be exacerbated by iatrogenic effects of treatment of MDD. The most commonly used atypical antipsychotics, mood stabilizers and antidepressants result in some degree of weight gain.16,17 For example, atypical antipsychotics, such as olanzepine, induce substantial weight gain.18 This can be somewhat mitigated by switching to other medications, such as clozapine; however, this is also known to increase body weight.18 Obesity is also positively associated with anxiety.19 Internalization of negative weight stereotypes may influence this association, as this stigma is associated with negative health consequences.20 For example, obesity is associated with stigma leading to interpersonal distress, which can lead to depression.20 Depression, especially atypical depression, can then result in reduced physical activity, emotional eating, increased alcohol consumption and further development of obesity. While these psychosocial factors underlie the association between obesity and depression, there are several other neurobiological and metabolic factors that may causally underlie vulnerability to these disorders.