Obesity-Related Differences in Amygdala and Hippocampus Volume and Metabolism in Major Depressive Disorder: Implications for Antidepressant Treatment

The link between obesity and depression is bidirectional and antidepressant efficacy is reduced in obese individuals. To probe this mechanism, anthropometric measures (body mass index [BMI] and waist circumference [WC]) from 85 participants (n = 56 females, n = 29 males) with Major Depressive Disorder (MDD) were acquired. Participants then received simultaneous positron emission tomography (PET)/magnetic resonance imaging (MRI) before and after treatment with a double-blind randomized trial of escitalopram. Linear mixed models were used to examine the association of continuous and categorical anthropometric measures with pretreatment amygdala and hippocampus volumes and metabolism, controlling for covariates. Similar models assessed the association with percent change in brain volume and metabolism with treatment, controlling for treatment type. Pretreatment, obesity was significantly positively associated with amygdala (p = 0.0160 and 0.0154, for WC and BMI, respectively) and hippocampus (p = 0.0221 for BMI) volume, but not metabolism. With treatment, each additional inch of WC (or each lb/in ² of BMI) was associated with a -0.38% (or -0.26%) treatment-induced change in amygdala volume. In fact, past 37.29 in (border of increased risk for males, substantially increased risk for females) or 30.63 lb/in ² (obese range), the percent change in amygdala volume with treatment shifts from positive (increasing) to negative (decreasing). Further, for every 1 lb/in ² in BMI, there was a 1.03% (amygdala) or 0.99% (hippocampus) increase in metabolism with treatment. This multimodal study is the first to suggests that obesity-related factors may alter the structure and metabolism of the amygdala and hippocampus, potentially reducing antidepressant effectiveness in MDD.