The Stress-Antidepressant-diet (SAD) Paradigm and Weight Gain

Suhyun Lee, Martin Lewis, Claudio A. Mastronardi, Rachel Li, Paul Smith, Julio Licinio, Ma-Li Wong

Research output: Contribution to conferencePoster


Background: Antidepressants are the most frequently prescribed class of drugs; about 264 million antidepressant prescription were issued in the US in 2011. The use of most antidepressants is associated with weight gain; however, the pathophysiogical mechanisms of this association are still unknown. Our lab has developed an animal model that addresses “paradoxical weight loss” by investigating the interactions between short-term exposure to stress, antidepressant administration and exposure, and long-term exposure to an obesogenic high-fat diet.

Methods: Male Sprague-Dawley rats are subjected to the following paradigm: Short-term exposure to recurrent restraint stress and antidepressants for 2 weeks, followed by long-term high-fat diet intake, were studied for 295 days. We have classified animals as obesity-prone (upper 50% of body weight) or obesity-resistant (lower 50% of body weight). On study day 295, animals were sacrificed and various organs were collected and weighed. Measurements: Body weight, food intake ratio, behavioural testing, and bone weight.

Results: Obesity-prone rats treated with fluoxetine (RFX) had increased body weight, in comparison to the control group treated with saline (RC) and non-restraint control group (NRCF). The RFX and the imipramine treated group (RIM) groups had significantly lower food intake ratio in comparison to the non-restraint control group (NRCF). The obesity-prone RFX rats had significantly longer body length in comparison to the NRCF, RC and RIM groups. The obesity-prone RFX and RIM rats had significantly larger body circumference in comparison to two control groups. The RFX group were significantly less anxious and had heavier bones.

Conclusions: Our data suggest that the association between stress, exposure to antidepressant treatment, and the long-term intake of an obesogenic high-fat diet is associated with greater weight gain, bone weight and body length in obese-prone RFX rats. We show that animals with antidepressant exposure had a greater degree of weight gain after long-term exposure to an obesogenic diet than animals on the same diet, but without exposure to antidepressants. We advance here the novel concept that antidepressant exposure represents a long-term risk factor for obesity and present the testable hypothesis that antidepressant exposure might be a major hidden contributor to our current obesity epidemic.
Original languageEnglish
Publication statusPublished or Issued - Dec 2015
Event54th Annual Meeting of the American College of Neuropsychopharmacology (ACNP) - Hollywood, United States
Duration: 6 Dec 201510 Dec 2015


Conference54th Annual Meeting of the American College of Neuropsychopharmacology (ACNP)
Country/TerritoryUnited States

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