Smaller Hippocampal Volume in Posttraumatic Stress Disorder: A Multisite ENIGMA-PGC Study: Subcortical Volumetry Results From Posttraumatic Stress Disorder Consortia

Abstract

Background: Many studies report smaller hippocampal and amygdala volumes in posttraumatic stress disorder (PTSD), but findings have not always been consistent. Here, we present the results of a large-scale neuroimaging consortium study on PTSD conducted by the Psychiatric Genomics Consortium (PGC)-Enhancing Neuroimaging Genetics through Meta-Analysis (ENIGMA) PTSD Working Group.

Methods: We analyzed neuroimaging and clinical data from 1868 subjects (794 PTSD patients) contributed by 16 cohorts, representing the largest neuroimaging study of PTSD to date. We assessed the volumes of eight subcortical structures (nucleus accumbens, amygdala, caudate, hippocampus, pallidum, putamen, thalamus, and lateral ventricle). We used a standardized image-analysis and quality-control pipeline established by the ENIGMA consortium.

Results: In a meta-analysis of all samples, we found significantly smaller hippocampi in subjects with current PTSD compared with trauma-exposed control subjects (Cohen's d = -0.17, p = .00054), and smaller amygdalae (d = -0.11, p = .025), although the amygdala finding did not survive a significance level that was Bonferroni corrected for multiple subcortical region comparisons (p < .0063).

Conclusions: Our study is not subject to the biases of meta-analyses of published data, and it represents an important milestone in an ongoing collaborative effort to examine the neurobiological underpinnings of PTSD and the brain's response to trauma.

Keywords: Amygdala; Childhood trauma; Gender differences; Hippocampus; PTSD; Structural MRI.

Figure 1

Cohen’s d estimate of the association between posttraumatic stress disorder and subcortical brain volumes as well as confidence intervals on effect size. Included is a primary analysis adjusted for age, gender, and intracranial volume and followup analyses with left and right volumes analyzed separately. A plus sign (+) indicates that the comparison of posttraumatic stress disorder cases and control subjects was significant at the p < .05 level. An asterisk (*) indicates that the comparison was significant after a Bonferroni correction for the eight subcortical regions examined (p < .0063). Lat., lateral.

Figure 2

Forest plot of the effect size estimates and 95% confidence intervals of 16 participating sites and meta-analyses for the association between mean hippocampal volume and posttraumatic stress disorder. For detailed descriptions and full names of participating sites see Supplemental Tables S1–S3. Adult meta-analysis includes all sites but University of Washington. The military meta-analysis includes Department of Defense (DoD) Alzheimer’s Disease Neuroimaging Initiative (ADNI), Duke/Durham Veterans Administration (VA), the VA Translational Center for Traumatic Brain Injury and Stress Disorders (TRACTS), University Medical Center (UMC) Utrecht, and West Haven VA. The civilian meta-analysis includes the Academic Medical Center (AMC) Amsterdam, Cape Town, Emory Grady Trauma Project (GTP), McLean, University of New South Wales (UNSW), University of Sydney (U of Sydney), University of Michigan (U Michigan), VU University Medical Center (VUMC) Amsterdam, Western Ontario, and Yale studies.

Figure 3

Cohen’s d estimate of the association between posttraumatic stress disorder and subcortical brain volumes as well as confidence intervals on effect size for subsets of the data. Included are analyses of men and women analyzed separately, as well as all adult samples (nonpediatric), military, and civilian datasets meta-analyzed separately. A plus sign (+) indicates that the comparison of PTSD cases and control subjects was significant at the p < .05 level. An asterisk (*) indicates that the comparison was significant after a Bonferroni correction for the eight subcortical regions examined (p < .0063). Lat., lateral.