Obesity-related differences in amygdala and hippocampal volume and metabolism before and after a placebo-controlled antidepressant trial in major depressive disorder

This study examined the association between obesity, measured by waist circumference (WC) and Body Mass Index (BMI), and neurobiology of the treatment/placebo response in depression. 85 participants (56 females, 29 males) with Major Depressive Disorder (MDD) were imaged using PET/MRI before and after a double-blind, randomized escitalopram trial. Analyses were pooled across interventions to investigate primary imaging associations. Linear mixed models examined associations between obesity measures and amygdala and hippocampal volume and metabolism. Preintervention obesity was significantly positively associated with amygdala and hippocampus volume, but not metabolism. Successful treatment is often associated with an increase in volume and a reduction in metabolism in these regions. However, greater WC and BMI were associated with decreases in amygdala volume following treatment/placebo. And greater BMI was associated with increases in amygdala and hippocampus metabolism following treatment/placebo. Importantly, however, these neurobiological changes were not associated with differential improvement in depression severity. Overall, this multimodal study shows obesity-related factors are associated with intervention-related neurobiological changes in MDD; however, additional research is needed to clarify whether these alterations correspond to meaningful variation in symptom improvement.