Altered white matter microstructural organization in posttraumatic stress disorder across 3047 adults: results from the PGC-ENIGMA PTSD consortium.

A growing number of studies have examined alterations in white matter organization in people with posttraumatic stress disorder (PTSD) using diffusion MRI (dMRI), but the results have been mixed which may be partially due to relatively small sample sizes among studies. Altered structural connectivity may be both a neurobiological vulnerability for, and a result of, PTSD. In an effort to find reliable effects, we present a multi-cohort analysis of dMRI metrics across 3047 individuals from 28 cohorts currently participating in the PGC-ENIGMA PTSD working group (a joint partnership between the Psychiatric Genomics Consortium and the Enhancing NeuroImaging Genetics through Meta-Analysis consortium). Comparing regional white matter metrics across the full brain in 1426 individuals with PTSD and 1621 controls (2174 males/873 females) between ages 18-83, 92% of whom were trauma-exposed, we report associations between PTSD and disrupted white matter organization measured by lower fractional anisotropy (FA) in the tapetum region of the corpus callosum (Cohen's d = -0.11, p = 0.0055). The tapetum connects the left and right hippocampus, for which structure and function have been consistently implicated in PTSD. Results were consistent even after accounting for the effects of multiple potentially confounding variables: childhood trauma exposure, comorbid depression, history of traumatic brain injury, current alcohol abuse or dependence, and current use of psychotropic medications. Our results show that PTSD may be associated with alterations in the broader hippocampal network.

White matter integrity alterations in post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) is a debilitating condition which can develop after exposure to traumatic stressors. Seventy-five adults were recruited from the community, 25 diagnosed with PTSD along with 25 healthy and 25 trauma-exposed age- and gender-matched controls. Participants underwent clinical assessment and magnetic resonance imaging. A previous voxel based morphometry (VBM) study using the same subject cohort identified decreased grey matter (GM) volumes within frontal/subcortical brain regions including the hippocampus, amygdala, and anterior cingulate cortex (ACC). This study examines the microstructural integrity of white matter (WM) tracts connecting the aforementioned regions/structures. Using diffusion tensor imaging, we investigated the integrity of frontal/subcortical WM tracts between all three subject groups. Trauma exposed subjects with and without PTSD diagnosis were identified to have significant disruption in WM integrity as indexed by decreased fractional anisotropy (FA) in the uncinate fasciculus (UF), cingulum cingulate gyrus (CCG), and corpus callosum (CC), when compared with healthy non-trauma-exposed controls. Significant negative correlations were found between total Clinician Administered PTSD scale (CAPS) lifetime clinical subscores and FA values of PTSD subjects in the right UF, CCG, CC body, and right superior longitudinal fasciculus (SLF). An analysis between UF and SLF FA values and VBM determined rostral ACC GM values found a negative correlation in PTSD subjects. Findings suggest that compromised WM integrity in important tracts connecting limbic structures such as the amygdala to frontal regions including the ACC (i.e., the UF and CCG) may contribute to impairments in threat/fear processing associated with PTSD.

Frontal and subcortical grey matter reductions in PTSD.

Post-traumatic stress disorder (PTSD) is characterised by a range of debilitating psychological, physical and cognitive symptoms. PTSD has been associated with grey matter atrophy in limbic and frontal cortical brain regions. However, previous studies have reported heterogeneous findings, with grey matter changes observed beyond limbic/frontal areas. Seventy-five adults were recruited from the community, 25 diagnosed with PTSD along with 25 healthy and 25 trauma exposed age and gender matched controls. Participants underwent clinical assessment and magnetic resonance imaging. The data-analyses method Voxel Based Morphometry (VBM) was used to estimate cortical grey matter volumes. When compared to both healthy and trauma exposed controls, PTSD subjects demonstrated decreased grey matter volumes within subcortical brain regions-including the hippocampus and amygdala-along with reductions in the anterior cingulate cortex, frontal medial cortex, middle frontal gyrus, superior frontal gyrus, paracingulate gyrus, and precuneus cortex. Significant negative correlations were found between total CAPS lifetime clinical scores/sub-scores and GM volume of both the PTSD and TC groups. GM volumes of the left rACC and right amygdala showed a significant negative correlation within PTSD diagnosed subjects.

A systematic review and meta-analysis of magnetic resonance imaging measurement of structural volumes in posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is a debilitating condition associated with mild to moderate cognitive impairment and with a prevalence rate of up to 22% in veterans. This systematic review and quantitative meta-analysis explore volumetric differences of three key structural brain regions (hippocampus, amygdala and anterior cingulate cortex (ACC)), all of which have been implicated in dysfunction of both salience network (SN) and default mode network (DMN) in PTSD sufferers. A literature search was conducted in Embase, Medline, PubMed and PsycINFO in May 2013. Fifty-nine volumetric analyses from 44 articles were examined and included (36 hippocampus, 14 amygdala and nine ACC) with n=846 PTSD participants, n=520 healthy controls (HCs) and n=624 traumatised controls (TCs). Nine statistical tests were performed for each of the three regions of interest (ROIs), measuring volume differences in PTSD subjects, healthy and traumatised controls. Hippocampal volume was reduced in subjects with PTSD, with a greater reduction in the left hippocampus. A medium effect size reduction was found in bilateral amygdala volume when compared with findings in healthy controls; however, no significant differences in amygdala volume between PTSD subjects and trauma-exposed controls were found. Significant volume reductions were found bilaterally in the ACC. While often well matched with their respective control groups, the samples of PTSD subjects composed from the source studies used in the meta-analyses are limited in their homogeneity. The current findings of reduced hippocampal volume in subjects with PTSD are consistent with the existing literature. Amygdala volumes did not show significant reductions in PTSD subjects when compared with volumes in trauma-exposed controls-congruous with reported symptoms of hypervigilance and increased propensity in acquisition of conditioned fear memories-but a significant reduction was found in the combined left and right hemisphere volume analysis when compared with healthy controls. Bilateral volume reductions in the ACC may underpin the attentional deficits and inabilities to modulate emotions that are characteristically associated with PTSD patients.