Lower Gyrification of the Ventromedial Prefrontal Cortex in Posttraumatic Stress Disorder: An ENIGMA-PTSD Study

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Background: Cortical gyrification involves the formation of folds in the cerebral cortex, coinciding with key neurodevelopmental processes. Its strong correlation with increased cortical surface area and decreased cortical thickness may improve cortical signaling efficiency by decreasing cortico-cortical distance. Differences in brain structure have been found in posttraumatic stress disorder (PTSD), yet few small studies have examined cortical gyrification. Methods: Gyrification was quantified using FreeSurfer’s Local Gyrification Index (lGI), derived from 3-dimensional T1-weighted volumetric brain magnetic resonance imaging in 1876 participants (PTSD n = 789, control n = 1087) across 24 sites from the ENIGMA-PGC (Enhancing Neuro Imaging Genetics through Meta-Analysis and Psychiatric Genomics Consortium) PTSD working group. Using a region of interest–based approach, we fitted a linear mixed-effects model with age (mean = 35.6, SD = 9.23, range = 8–95), sex (female = 967 [52%], male = 909 [48%]), pial surface area, PTSD, and random site effects to test associations between PTSD diagnosis/severity and regional lGI. We examined moderating effects of depression, childhood trauma, age, and sex. Results: PTSD diagnosis and severity were both associated with lower lGI for the right medial orbitofrontal and right rostral anterior cingulate cortices. The interaction of PTSD and age was associated with lower lGI for the rostral middle frontal cortex bilaterally. Contrasting comorbid PTSD and major depressive disorder with the PTSD-only group showed that comorbidity was associated with lower lGI in the left inferior and medial temporal cortices. Conclusions: Lower lGI, which is associated with impaired signaling efficiency, was observed in the PTSD group compared with the control group for the ventromedial prefrontal cortex, a region that has been strongly implicated in associative fear learning and extinction. It is possible that PTSD accelerates the typical age-associated decline in lGI of the rostral middle frontal cortices.

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Hussain, A., Baird, C. L., Huggins, A. A., Russell, C. C., Sun, D., Rangel-Jimenez, L., Abdallah, C. G., Angstadt, M., May, G., Berg, H., Blackford, J. U., Cisler, J., Daniels, J. K., Davenport, N. D., Davidson, R. J., Densmore, M., Disner, S. G., El-Hage, W., Etkin, A., … Morey, R. A. (2026). Lower Gyrification of the Ventromedial Prefrontal Cortex in Posttraumatic Stress Disorder: An ENIGMA-PTSD Study. Biological Psychiatry Global Open Science. https://doi.org/10.1016/j.bpsgos.2025.100679