Relationship of recent stress to amygdala volume in depressed and healthy adults

Background: The amygdala is an integral part of the extrahypothalamic stress-response system, and its volume related to childhood trauma has been studied, but less is known of associations with recent stressful life events. Amygdala volume differences also have been studied in depression, with conflicting results. We hypothesized that effects of stress may be a confound for amygdala volumetric differences in the context of depression.

Methods: Right-handed participants (n=61) experiencing a major depressive episode during major depressive disorder (n=40) or bipolar depression (n=21) and healthy volunteers (n=60) underwent 1.5T magnetic resonance imaging (MRI). The amygdala perimeter was manually traced with an electronic mouse, based on anatomical landmarks on consecutive coronal slices, by raters blind to diagnosis. The effects of stress on amygdala volume were examined in linear regression models with self-reported physical/sexual abuse or highest category score on the St. Paul-Ramsey scale of stressful life events within the past 6 months as predictors, testing separately for age, sex, race, and depression status as covariates.

Results: Diagnostic groups did not differ significantly with respect to mean age (depressed, 37.8±11.8yrs; healthy, 34.9±13.8yrs) or proportion of males (depressed, 39%, healthy, 50%). We found no association between physical and/or sexual abuse history and amygdala volume. Life stress within the last six months, however, was associated with smaller left amygdala volume. The association between stress and amygdala volume did not differ by diagnostic group.

Limitations: Most depressed patients were off medications for at least 2 weeks; however, this may not have been long enough to reverse effects of medications on amygdala structure.

Conclusions: That life stress of relatively short duration was associated with amygdala size in the entire sample, while temporally distant life stress was not, suggests that amygdala volume changes may occur rapidly and reversibly, and independent of depression status.