September 26, 2012

Obesity Comorbidity With Major Depressive Disorder

Author Picture

Robert D. Levitan, MD

University of Toronto, Toronto, Ontario, Canada


One of the greatest challenges in psychiatric and medical research is clinical heterogeneity. To address this complexity head-on, we must, wherever possible, refine the target phenotypes that we study and treat.

A good example of a phenotype in need of refinement can be found in the common and challenging problem of depression-obesity comorbidity. While over 120 articles have been published on this topic to date, almost all have considered depression as a unitary diagnosis, ignoring the fundamental importance of neurovegetative depressive subtypes that have primary relevance to weight gain. This lack of attention is highly problematic, given that one major subtype of MDD (atypical depression) is associated with increased appetite and overeating, while another (classic melancholia) is associated with decreased appetite and weight loss in most cases.

The main finding from our study, as hypothesized a priori, is that atypical depression is, in fact, associated with a much higher risk for obesity than is melancholia, which, in fact, has no increased risk for obesity relative to the population as a whole. These findings were not significantly influenced by gender, age, or whether depression was active in the past year.

This finding points to a need for significant refinement of study hypotheses and phenotyping for future work on depression-obesity comorbidity, which should, in turn, improve treatment options over time.

Financial disclosure:Dr Levitan had no relevant personal financial relationships to report.​

Category: Depression
Link to this post:
Related to "Obesity Comorbidity With Major Depressive Disorder"

12 thoughts on “Obesity Comorbidity With Major Depressive Disorder

  1. Did you look into adverse childhood events in each group to see if the atypical group had more adverse childhood events or higher ACE scores as compared to the other groups?
  2. Is over eating in atypical depression providing some benefit to the depressed person vis-a-vis altered hormonal state or neurotransmitter levels. Is the over eating depressed patient in fact attempting to self medicate in some way? And may this be why so many depressed patients after weight loss surgery find that there depression worsens?
    You indeed provide many provocative questions that need study – but I believe that the answers may be more complex than simply obesity leads to depression or visa-versa.
  3. It should be noted that the weight gain associated with some atypical antipsychotics tends to be most pronounced the first 8 weeks and is greatest in normal and underweight individuals rather than the obese.
  4. One of the problems I see is that people with diseases like MDD and assofiated childlike developmental level are expected to “take instruction and apply it consistently”, “be consistent in implementing knowledge and a strategy”, etc. This is an example of poor dx, and poor treatment design. Simple health counseling (15 min), prescribing a “diet and exercise”, and minimal intervention and then jump to the other extreme of Bariatric Surgury when this repeatedly fails is the state of most Primary Care Centers. It is we that are primative in our dx workups, staffing of Primary Care Centers (without psychologists and psychiatrists), and w/out scientifically conceived interventions. Our interventions fit us, but don’t fit these patients! Are we treating our preferences or “the patient”!
  5. any chronic infection any where any chronic disease (involving any organ)may lead to ;or eventually lead to depression…but the severity of the infection differs..and depends on many factors
  6. Over many years I have seen a very high percentage of trauma survivors who have food and obesity as central issues. Whether it is food as comfort / self-reward or such issues as being morbidly obese as a protection against sexual attention, the patients with substantial weight gain have a very high frequency of trauma.

    Much of the “atypicality” described over the years seems to me to be trauma related pathology.

  7. Early life adversity, even in utero, may lead to obesity. Central obesity related to increased sympathetic nervous system tone and high caloric intake can involve infiltration of macrophages into the omental fat mass. Adipocytes and macrophages may release excess pro-inflammatory cytokines that can lead to glucocorticoid receptor desensitization and insulin resistance. Many patients with atypical depression are hypocortisolemic which along with gc receptor desensitization could contribute to a persistent “inflammatory” state both in the periphery but also the CNS.

Leave a Reply


Browse By Author



Browse By Author

Sign-up to stay
up-to-date today!


Already registered? Sign In

Original Research

Effect of Zuranolone on Concurrent Anxiety and Insomnia Symptoms in Women With Postpartum Depression

Zuranolone was associated with improvements in depressive and anxiety symptoms and was beneficial for insomnia and patient-perceived...