Amygdala volume changes in posttraumatic stress disorder in a large case-controlled veterans group.

Context: Smaller hippocampal volumes are well established in posttraumatic stress disorder (PTSD), but the relatively few studies of amygdala volume in PTSD have produced equivocal results.

Objective: To assess a large cohort of recent military veterans with PTSD and trauma-exposed control subjects, with sufficient power to perform a definitive assessment of the effect of PTSD on volumetric changes in the amygdala and hippocampus and of the contribution of illness duration, trauma load, and depressive symptoms.

Design: Case-controlled design with structural magnetic resonance imaging and clinical diagnostic assessments. We controlled statistically for the important potential confounds of alcohol use, depression, and medication use.

Setting: Durham Veterans Affairs Medical Center, which is located in proximity to major military bases.

Patients: Ambulatory patients (n = 200) recruited from a registry of military service members and veterans serving after September 11, 2001, including a group with current PTSD (n = 99) and a trauma-exposed comparison group without PTSD (n = 101).

Main outcome measure: Amygdala and hippocampal volumes computed from automated segmentation of high-resolution structural 3-T magnetic resonance imaging.

Results: Smaller volume was demonstrated in the PTSD group compared with the non-PTSD group for the left amygdala (P = .002), right amygdala (P = .01), and left hippocampus (P = .02) but not for the right hippocampus (P = .25). Amygdala volumes were not associated with PTSD chronicity, trauma load, or severity of depressive symptoms.

Conclusions: These results provide clear evidence of an association between a smaller amygdala volume and PTSD. The lack of correlation between trauma load or illness chronicity and amygdala volume suggests that a smaller amygdala represents a vulnerability to developing PTSD or the lack of a dose-response relationship with amygdala volume. Our results may trigger a renewed impetus for investigating structural differences in the amygdala, its genetic determinants, its environmental modulators, and the possibility that it reflects an intrinsic vulnerability to PTSD.