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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.

Adverse childhood experiences (ACEs) potentially contribute to posttraumatic stress disorder (PTSD) after adult trauma exposure, but underlying brain changes remain unclear. The present study tested relationships between ACEs, whole thalamus and thalamic nuclei volumes, and post-trauma stress symptoms (PTSS) after adult trauma. Trauma survivors (n = 101) completed the Childhood Trauma Questionnaire (CTQ), the PTSD checklist-special stressor version 5 (PCL), and a structural magnetic resonance imaging (sMRI) scan within post-trauma 2 weeks. At post-trauma 3 months, survivors completed a second PCL survey and a PTSD diagnosis interview using the Clinician-Administered PTSD Scale (CAPS). CTQ scores significantly positively correlated with PCL scores at post-trauma 2 weeks and 3 months (respective p's0.01 and0.001). CTQ scores significantly negatively correlated with whole thalamus and 7 thalamic nuclei volumes at post-trauma 2 weeks in the PTSD (N = 50), but not the non-PTSD (N = 51) group. Whole thalamus and 22 nuclei volumes significantly negatively correlated with PCL scores at post-trauma 3 months in the PTSD, but not the non-PTSD group. These results suggest ACEs negatively influence early post-trauma thalamic volumes which, in turn, are negatively associated with PTSS in survivors who develop PTSD.

Classification and prediction of posttraumatic stress disorder (PTSD) based on brain imaging measures is important because it could aid in PTSD diagnosis and clinical management of PTSD. The goal of the present study was to test the effectiveness of using cortical morphological measures (i.e. volume, thickness, and surface area) to classify PTSD cases and controls on 3571 individuals from the ENIGMA-Psychiatric Genomics Consortium PTSD Workgroup, the largest PTSD neuroimaging dataset to date. We constructed 6 feature sets from different demographic variables (age and sex) and cortical morphological measures and used four machine learning algorithms for classification: logistic regression, random forest, support vector machine, and multi-layer perceptron. We found that classifiers trained using only cortical morphological measures (any one of volume, thickness, or surface area) performed better than classifiers trained using only demographic variables. Among all 6 feature sets, combining demographic variables and all three cortical morphological measures yielded the best prediction accuracy, with area under the receiver operating characteristic curve (ROC AUC) scores ranging from 0.615 for logistic regression to 0.648 for random forest. These findings suggest that using cortical morphological measures only has modest prediction power for PTSD classification. Future studies that wish to produce clinically and practically significant findings should consider using whole brain morphological measures, as well as incorporating other neuroimaging modalities and relevant clinical and behavioral symptoms.

Accumulating evidence suggests traumatic experience can rapidly alter brain activation associated with emotion processing. However, little is known about acute changes in emotion neurocircuits that underlie PTSD symptom development. To examine acute alterations in emotion circuit activation and structure that may be linked to PTSD symptoms, thirty-eight subjects performed a task of appraisal of emotional faces as their brains were functionally and structurally studied with MRI at both two weeks and three months after motor vehicle collision (MVC). As determined by symptoms reported in the PTSD Checklist at three months, sixteen survivors developed probable PTSD, whereas the remaining 22 did not meet criteria for PTSD diagnosis (non-PTSD). The probable PTSD group had greater activation than the non-PTSD group in dorsal and ventral medial prefrontal cortex (dmPFC and vmPFC) while appraising fearful faces within two weeks after MVC and in left insular cortex (IC) three months after MVC. dmPFC activation at two weeks significantly positively correlated with PTSD symptom severity at two weeks (R = 0.462, P = 0.006) and three months (R = 0.418, p = 0.012). Changes over time in dmPFC activation and in PTSD symptom severity were also significantly positively correlated in the probable PTSD group (R = 0.641, P = 0.018). A significant time by group interaction was found for volume changes in left superior frontal gyrus (SFG, F = 6.048, p = 0.019) that partially overlapped dmPFC active region. Between two weeks and three months, left SFG volume decreased in probable PTSD survivors. These findings identify alterations in frontal cortical activity and structure during the early post-trauma period that appear to be associated with development of PTSD symptoms.