Metabolic Outcomes in Response to Chronic Stress and Antidepressant Treatment

Background: Antidepressant prescribing has risen 400% since the late 1980s; in parallel, obesity rates have doubled in adults and tripled in childhood during this period. Antidepressants treatment can lead to significant weight gain but the interplay between MDD, obesity and antidepressant treatment is complex. It is conceivable that nearly 25% of the cases of obesity may be attributable to the association with MDD and antidepressant use. Our lab has developed an animal model to understand the mechanisms of weight recovery after chronic stress, as we hypothesized that the effects of antidepressants on body weight would be unmasked by environmental factors, such as an obesogenic high-fat diet.

Methods: Male Sprague-Dawley rats were subjected to short-term exposure to recurrent restraint stress and antidepressants (fluoxetine or imipramine) for 2 weeks, followed by long-term high-fat diet intake for 295 days. Animals were then sacrificed and various organs were collected and weighed. Measurements: Body weight, food intake ratio, behavioural testing, and bone weight.

Results: Obesity-prone rats, defined as those within the upper 50% of body weight gain, treated with fluoxetine (FX) had increased body weight, in comparison to the control group treated with saline and non-restraint control group. The antidepressant-treated groups had significantly lower food intake ratio in comparison to the non-restraint control group. Obesity-prone FX rats had significantly longer body length in comparison to all other groups. Rats in the FX group were significantly less anxious and had heavier bones. New metabolic (leptin, adipose tissue gene expression) and IGF-1 data will be presented.

Conclusions: We present the conceptually novel and medically relevant, data-based conclusion that the interaction of stress, antidepressant treatment, and high-fat diet may have long-lasting body, bone allometric, and metabolic effects. In the context of CDC data showing that 11% of the US population over 12 years of age is on antidepressants, the clinical and public health implications of these findings are substantial.