White matter integrity alterations in post‐traumatic stress disorder

Abstract

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.

Rapid brain responses to affective pictures indicate dimensions of trauma‐related psychopathology in adolescents

“…Mueller-Pfeiffer et al (2013) also reported a diminished neural activity in the visual system in PTSD patients. Likewise, studies have reported white matter abnormalities, suggesting alterations in neural pathways (Akiki, Averill, & Abdallah, 2017;O'Doherty et al, 2018). An alternative explanation for the EPN inhibition might be an adaptive adjustment of emotion processing to arousing material after experiencing traumatic stress with a subsequent heightened arousal state.…”

Altered White Matter Microstructural Organization in Post-Traumatic Stress Disorder across 3,049 Adults: Results from the PGC-ENIGMA PTSD Consortium

“…Here we report microstructural evidence that structural connectivity between the left and right hippocampus may also be disrupted in PTSD. While many studies have reported that PTSD is associated with alterations in the cingulum bundle [9][10][11][12][13]16,18,21,[23][24][25][26][27][28][29]31,32,36 , which has a hippocampal component, the tapetum has not yet emerged for several possible reasons. Many prior studies took an ROI approach, which limited analyses to pre-determined regions that frequently omitted the tapetum, a small region often grouped with other tracts such as the splenium or posterior thalamic radiation.…”

“…Studies of white matter microstructure in PTSD have reported inconsistent results. The majority report that PTSD is associated with lower FA [8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24] , but some report higher FA [25][26][27][28][29][30][31] , higher and lower FA in different regions 32 , or null results [33][34][35] .…”

“…Alterations in the cingulum bundle are frequently reported [9][10][11][12][13]16,18,21,[23][24][25][26][27][28][29]31,32,36 , with differences also observed in the uncinate, corpus callosum, and corona radiata 14,16,18,19,24,26,29 . Inconsistent findings may be partially due to the use of hypothesis-driven rather than whole brain approaches, choice of analytic pipeline, selection of diffusion metrics, gender-specific studies, homogeneity of single cohort samples such as trauma-exposed vs. unexposed controls, and focus on military vs. civilian samples.…”

“…The ENIGMA DTI workflow 38 , which has successfully identified white matter compromise in schizophrenia 39 , bipolar disorder 40 , major depression 41 , and 22q11.2 deletion syndrome 42 , among others, was used by 28 cohorts to process their DTI data locally. We hypothesized the largest effects of compromised microstructure will be evident in the fronto-limbic tracts, such as the cingulum, uncinate, fornix, and corpus callosum; these tracts are strongly implicated in behavioral deficits of PTSD such as emotion regulation, working memory, and episodic memory 10,16,19,20,24,43 .…”