The association of PTSD symptom severity with amygdala nuclei volumes in traumatized youths

Abstract

The amygdala is a core component in neurobiological models of stress and stress-related pathologies, including post-traumatic stress disorder (PTSD). While numerous studies have reported increased amygdala activity following traumatic stress exposure and in PTSD, the findings regarding amygdala volume have been mixed. One reason for these mixed findings may be that the amygdala has been considered as a homogenous entity, while it in fact consists of several nuclei with unique cellular and connectivity profiles. Here, we investigated amygdala nuclei volumes of the basolateral and the centrocorticomedial complex in relation to PTSD symptom severity in 47 young survivors from the 2011 Norwegian terror attack 24-36 months post-trauma. PTSD symptoms were assessed 4-5, 14-15 and 24-36 months following the trauma. We found that increased PTSD symptom severity 24-36 months post-trauma was associated with volumetric reductions of all basolateral as well as the central and the medial nuclei. However, only the lateral nucleus was associated with longitudinal symptom development, and mediated the association between 4-5 months and 24-36 months post-trauma symptoms. The results suggest that the amygdala nuclei may be differentially associated with cross-sectional and longitudinal measures of PTSD symptom severity. As such, investigations of amygdala total volume may not provide an adequate index of the association between amygdala and stress-related mental illness.

Fig. 1. Amygdala nuclei and hippocampal subfield segmentation.

The result of an amygdala nuclei and hippocampus subfield segmentation from a representative individual. A: Sagittal and B: Axial view of the color coded subfields and nuclei. Yellow: anterior amygdala area, dark blue = corticoamygdala transition zone, orange = accessory basal nucleus, pink: basal nucleus, pale blue: lateral nucleus, light green = Hippocampus amygdala transition zone; red = CA1, dark green = CA3, beige = CA4, bright blue = subiculum, dark purple = parasubiciulum, light purple = hippocampal tail, pink = fimbria.

Fig. 2. Right amygdala nuclei volumes and PTSD symptom scores.

The association between the individual amygdala nuclei volumes and PTSD symptom scores (z-standardized) 24–36 months post-trauma. The regression lines represent the relationship between the dependent variable and the predictor of interest calculated without covariates. The gray shadings represent the 95% confidence interval. Outliers (residual values > 3.0 or <−3.0) are indicated by a red dot color.

Fig. 3. Mediation analysis.

The right lateral nucleus volume mediated the relationship between PTSD symptom load acquired 4–5 and 24–36 months following the trauma. *p < 0.05, **p < 0.005. Standardized coefficients in parenthesis.