Amygdala Nuclei Volume and Shape in Military Veterans With Posttraumatic Stress Disorder

Abstract

Background: The amygdala is a subcortical structure involved in socioemotional and associative fear learning processes relevant for understanding the mechanisms of posttraumatic stress disorder (PTSD). Research in animals indicates that the amygdala is a heterogeneous structure in which the basolateral and centromedial divisions are susceptible to stress. While the amygdala complex is implicated in the pathophysiology of PTSD, little is known about the specific contributions of the individual nuclei that constitute the amygdala complex.

Methods: Military veterans (n = 355), including military veterans with PTSD (n = 149) and trauma-exposed control subjects without PTSD (n = 206), underwent high-resolution T1-weighted anatomical scans. Automated FreeSurfer segmentation of the amygdala yielded 9 structures: basal, lateral, accessory basal, anterior amygdaloid, and central, medial, cortical, and paralaminar nuclei, along with the corticoamygdaloid transition zone. Subregional volumes were compared between groups using ordinary-least-squares regression with relevant demographic and clinical regressors followed by 3-dimensional shape analysis of whole amygdala.

Results: PTSD was associated with smaller left and right lateral and paralaminar nuclei, but with larger left and right central, medial, and cortical nuclei (p < .05, false discovery rate corrected). Shape analyses revealed lower radial distance in anterior bilateral amygdala and lower Jacobian determinant in posterior bilateral amygdala in PTSD compared with control subjects.

Conclusions: Alterations in select amygdala subnuclear volumes and regional shape distortions are associated with PTSD in military veterans. Volume differences of the lateral nucleus and the centromedial complex associated with PTSD demonstrate a subregion-specific pattern that is consistent with their functional roles in fear learning and fear expression behaviors.

Keywords: Amygdala; Amygdala nuclei; Shape analysis; Structural MRI; Trauma; U.S. Military.

Figure 1.

(A) FreeSurfer version 6.0 was used to segment 1-mm isotropic structural images to reveal amygdala subregions, which are indicated with color labels (medial nucleus = green, corticoamygdaloid transition area = dark blue, accessory basal amygdala = orange, basal amygdala = red, central amygdala = purple, anterior amygdaloid area = yellow, lateral amygdala = light blue). (B) Structural T1 scan provided for reference. Cortical and paralaminar nuclei are not pictured in this view.

Figure 2.

Effect size estimates measured as Cohen’s d for the left (blue) and right (orange) amygdala subregions. Positive effect size indicates smaller volume in the posttraumatic stress disorder group, and negative effect size indicates larger volume in the posttraumatic stress disorder group. Significance for each structure is indicated for false discovery rate–corrected **p < .01 and *p < .05.

Figure 3.

Posttraumatic disorder diagnosis was significantly related to (A) lower radial distance in the anterior aspects of the left (L) and right (R) amygdala and (B) lower Jacobian determinant in the posterior aspect of the left and right amygdala. Covariates include intracranial volume, age, gender, and scanner model.