Abstract
Studies of posttraumatic stress disorder (PTSD) report volume abnormalities in multiple regions of the cerebral cortex. However, findings for many regions, particularly regions outside commonly studied emotion-related prefrontal, insular, and limbic regions, are inconsistent and tentative. Also, few studies address the possibility that PTSD abnormalities may be confounded by comorbid depression. A mega-analysis investigating all cortical regions in a large sample of PTSD and control subjects can potentially provide new insight into these issues. Given this perspective, our group aggregated regional volumes data of 68 cortical regions across both hemispheres from 1379 PTSD patients to 2192 controls without PTSD after data were processed by 32 international laboratories using ENIGMA standardized procedures. We examined whether regional cortical volumes were different in PTSD vs. controls, were associated with posttraumatic stress symptom (PTSS) severity, or were affected by comorbid depression. Volumes of left and right lateral orbitofrontal gyri (LOFG), left superior temporal gyrus, and right insular, lingual and superior parietal gyri were significantly smaller, on average, in PTSD patients than controls (standardized coefficients = -0.111 to -0.068, FDR corrected P values < 0.039) and were significantly negatively correlated with PTSS severity. After adjusting for depression symptoms, the PTSD findings in left and right LOFG remained significant. These findings indicate that cortical volumes in PTSD patients are smaller in prefrontal regulatory regions, as well as in broader emotion and sensory processing cortical regions.
Highlights
Posttraumatic stress disorder (PTSD) affects millions of people globally [1]
PTSD patients had smaller volumes in right SFG, pars orbitalis of inferior frontal gyrus (IFG-PORB), MTG, superior and inferior parietal gyrus (SPG and IPG), and LING (Fig. 1)
Adding to previously reported volume reduction of superior temporal gyrus (STG) [17] and IG [8], we found smaller volumes of right SPG and LING in PTSD patients, which are consistent with gray matter density (GMD) differences in SPG [48] and LING [27, 48]
Summary
Posttraumatic stress disorder (PTSD) affects millions of people globally [1]. PTSD is characterized by intrusive memories of a traumatic event, avoidance of trauma-related circumstances, hyperarousal, and negative alterations in mood and cognition. Several structural magnetic resonance imaging (sMRI) studies comparing PTSD patients to controls report smaller volumes of brain regions related to these emotion functions, such as the hippocampus [7], cingulate, insula, and prefrontal cortices [8,9,10,11,12,13]; these results are inconsistent [14,15,16]. Some evidence points to reduced volumes in regions of parietal, temporal, and occipital cortices of PTSD patients [13, 17, 18] These findings have not been replicated and remain tentative [19], possibly due to small sample sizes or heterogeneity of samples and analyses across studies. Large samples permit nuanced analyses that can uncover underlying diagnostic heterogeneity by testing interactions with clinical variables
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