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.

Brain circuit dysfunction in post-traumatic stress disorder: from mouse to man

“…A sizeable literature demonstrates that there is reduced hippocampal volume in individuals with PTSD 75 . This observation has been established in studies of different types of trauma and different sample populations and was supported by the recent findings of the largest brain imaging study of PTSD to date 76 . However, whether trauma leads to hippocampal atrophy in individuals who develop PTSD or whether having small hippocampi predisposes an individual to PTSD remains controversial 77 .…”

Hippocampal subfields alterations in adolescents with post‐traumatic stress disorder

“…PTSD has been previously associated with hippocampal alterations in adults. Indeed, the ENIGMA consortium reported smaller hippocampal volumes on a large cohort (1,868 subjects) in civilians and veterans with PTSD compared to controls and, a negative correlation between hippocampal volumes and PTSD severity (Logue et al, ). In contrast, most of pediatric studies failed to report any hippocampal alterations in children and adolescents with PTSD compared to healthy subjects (Morey et al, ; Woon & Hedges, ) (but see (Mutluer et al, )).…”

“…These intrusions could be related to an alteration of the hippocampal structure, known to be involved in contextual memory (Maren et al, ). Indeed, several neuroimaging studies reported smaller hippocampal volumes in adults suffering from PTSD compared to people who lived a traumatic experience without PTSD and compared to healthy controls (Logue et al, ; Pitman et al, ).…”

A review of hippocampal activation in post‐traumatic stress disorder

“…The hippocampus is implicated in emotional memory formation and contextualization (Dere, Pause, & Pietrowsky, 2010), and a large body of the literature over the last 20 years has documented smaller hippocampal volumes in PTSD (Chao, Weiner, & Neylan, 2013;Childress et al, 2013;Logue et al, 2018; for latest review, see also Nelson & Tumpap 2017). Furthermore, evidence suggests that smaller hippocampal volume prior to trauma exposure is a risk factor for PTSD development and persistence (Gilbertson et al, 2002;Van Rooij et al, 2015).…”