A Recipe for Homemade Obesity: The Association Between Depression, Obesity, and Cognitive Deficits

December 31, 2020
Hartej Gill

Roger S. Mcintyre, MD, FRCPC

Psychiatric Times, Psychiatric Times Vol 37, Issue 12, Volume 37, Issue 12

Evidence suggests that physical activity aids in alleviating mild to moderate symptoms of depression in patients and may promote clinically significant antidepressant effects.


The unintended negative consequences of the coronavirus disease 2019 (COVID-19) pandemic continues to be a problem. Reduced social interaction and closure of public places, along with increased home confinement, has led to a sharp decrease in physical activity, a steady increase in food intake, and a rise in the risk of obesity.1 Stress has similarly impacted sleep, unhealthy eating, and even increased consumption of alcohol.

Public health and economic crises have been associated with serious, long-lasting negative impact on individual and population-based mental health outcomes. Indeed, a recent meta-analysis found higher rates of anxiety, depression, posttraumatic stress disorder, psychological distress, and stress during the COVID-19 pandemic.2 To further complicate matters, individuals are less likely to seek non-emergent health care, including care for mental disorders, during the pandemic.

Obesity and depression

Related health consequences of obesity such as hypertension and diabetes mellitus are a major source of morbidity.3 Stress, fatigue, physical inactivity, and a sedentary lifestyle can advance obesity and, subsequently contribute to a number of mental health disorders.4 Depression and obesity share a bidirectional relationship, where the presence of one disease increases the risk for developing the other (Figure).5 Increased carbohydrate consumption, a risk factor for obesity, is common in patients with depression. The presence of obesity often has a chronic course of illness and can result in poor treatment response in depression.

Patients with depression in primary care settings are predominantly treated with antidepressants as a first-line treatment option, with 79% of primary care physicians prescribing antidepressants to these patients.6 Recent studies have shown that antidepressant medications can contribute to weight gain through various mechanisms, including increased food consumption and abnormal metabolic processes.7 Reductions in depressive symptoms and antidepressant usage may coincide with weight loss (as seen with bariatric surgery patients), and this underscores the importance of monitoring the increasing rates of obesity.

Cognitive impairments

For the last 2 decades, depressive disorders have consistently ranked amongst the top 5 illnesses for years of life lived with a disability.8 Cognitive deficits is a core symptom of depression, and it often persist between affective episodes and beyond the remission of mood symptoms.9 Executive functioning, attention, memory, and learning can be affected.10 Obesity also contributes to impairments in cognition; individuals with obesity exhibit significantly impaired cognitive functioning and structural changes in brain regions associated with executive functioning.11 Moreover, in individuals with obesity, cognitive impairments predict lower weight loss success, poor treatment adherence, and decreased physical functioning.12,14

Individuals with a longer duration of illness and a higher frequency of depressive episodes are more likely to experience cognitive impairments. Persistent cognitive impairment contributes to consequences in occupational and social domains.14 In particular, evidence from adults with mood disorders implicates cognitive impairment as a mediator of workplace function and attendance, as well as patient-reported outcomes (eg, quality of life).15 Approximately 15% of patients with major depressive disorder attribute their unemployment to cognitive symptoms. Unfortunately, few treatments, including psychotropic medications, have proven effective in improving cognitive function in adults with mood disorders, especially in cases of treatment resistance.

Inflammation comorbidity

Patients with comorbid depression and obesity often demonstrate higher levels of baseline inflammation, which is characterized by a higher level of inflammatory cytokines (a type of signaling molecule that promotes inflammation). Likewise, obesity involves a pro-inflammatory state. Conversely, findings have shown improved cognition is linked to a reduction in inflammation.3 Indeed, in a meta-analysis evaluating inflammation and treatment response, researchers found increased levels of inflammatory cytokines in patients with depression. In cases that successfully responded to treatment, the levels of inflammatory cytokines were decreased.20

There are several proposed mechanisms that may mediate the relationship between chronic stress, inflammation, and mood disorders. Stressful experiences have been shown to increase production of cortisol. Glucocorticoids increase activities of the sympathetic system, such as heart rate and blood pressure, to reduce the stress response. However, if this system is dysregulated, chronic stress and cortisol production can lead to the desensitization of the glucocorticoid receptors. It can be conjectured that the dysregulation of the inflammatory pathway is also worsened by the presence of insulin resistance and increase in adipocytes. The bidirectional relationship between the 2 illnesses and the co-occurrence of an inflammatory state underscores the involvement of inflammation in the pathophysiology of depression and obesity.


Evidence suggests that physical activity aids in alleviating mild to moderate symptoms of depression in patients and may promote clinically significant antidepressant effects. For more severe cases of depression, exercise works well in conjunction with other treatments (ie, pharmacological).16 Exercise may also help improve cognition in individuals with depression. In a study investigating the dose-dependent effects of exercise on cognition in patients with depression, high-intensity exercise was associated with improvements in executive function and working memory tasks. Meanwhile, other cognitive domains, such as attention, visual memory, and spatial planning, improved regardless of dose.17 Therefore, it is importan that adequate social and physical activities are integrated into treatment plans to promote well-being.

Mr Gill is a researcher at the Canadian Rapid Treatment Center of Excellence and the Institute of Medical Science at the University of Toronto. Dr McIntyre is a professor of psychiatry and pharmacology at the University of Toronto, and Head of the Mood Disorders Psychopharmacology Unit for the University Health Network, Toronto, Canada.


1. Chang T, Chou C, Chang L. Effect of obesity and body mass index on coronavirus disease 2019 severity: A systematic review and meta‐analysis.

2 .Xiong J, Lipsitz O, Nasri F, et al. Impact of COVID-19 pandemic on mental health in the general population: A systematic review.

3. Alosco ML, Spitznagel MB, Strain G, et al. Improved serum leptin and ghrelin following bariatric surgery predict better postoperative cognitive function.

4. Sarris J, O’Neil A, Coulson, et al. Lifestyle medicine for depression.

5. Luppino FS, de Wit LM, Bouvy PF, et al. Overweight, obesity, and depression: a systematic review and meta-analysis of longitudinal studies.

6. Barkil-Oteo A. Collaborative care for depression in primary care: how psychiatry could “troubleshoot” current treatments and practices.

7. Gill H, Gill B, El-Halabi S, et al. Antidepressant Medications and Weight Change: A Narrative Review. (Silver Spring)

8. Collaborators G 2016 ORF, GBD 2016 Occupational Risk Factors Collaborators. Global and regional burden of disease and injury in 2016 arising from occupational exposures: a systematic analysis for the Global Burden of Disease Study 2016.

9. McIntyre RS, Lee Y. Cognition in major depressive disorder: a “Systemically Important Functional Index” (SIFI).

10. Motter JN, Pimontel MA, Rindskopf D, Devanand DP, Doraiswamy PM, Sneed JR. Computerized cognitive training and functional recovery in major depressive disorder: A meta-analysis.

11. Spitznagel MB, Garcia S, Miller LA, et al. Cognitive function predicts weight loss after bariatric surgery.

12. Rasmussen LJH, Caspi A, Ambler A, et al. Association of Neurocognitive and Physical Function With Gait Speed in Midlife.

13. Baune BT, Air T. Clinical, Functional, and Biological Correlates of Cognitive Dimensions in Major Depressive Disorder – Rationale, Design, and Characteristics of the Cognitive Function and Mood Study (CoFaM-Study).

14. McIntyre RS, Lee Y, Mansur RB. Treating to target in major depressive disorder: response to remission to functional recovery.

15. Strawbridge R, Arnone D, Danese A, Papadopoulos A, Herane Vives A, Cleare AJ. Inflammation and clinical response to treatment in depression: A meta-analysis.

16. Schuch FB, Vancampfort D, Richards J, et al. Exercise as a treatment for depression: A meta-analysis adjusting for publication bias.

17. Greer TL, Grannemann BD, Chansard M, et al. Dose-dependent changes in cognitive function with exercise augmentation for major depression : results from the TREAD study.

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