Lower Gyrification of the Ventromedial Prefrontal Cortex in Posttraumatic Stress Disorder: An ENIGMA-PTSD Study
Abstract
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.
Related
- Emotion knowledge is structured in a grid-like coordinate system in the human ventromedial prefrontal cortex
- Is damage to the ventromedial prefrontal cortex associated with impaired empathy? A neuropsychological study using an empathy motivation task
- Structural Covariance of Early Visual Cortex Is Negatively Associated With Posttraumatic Stress Disorder Symptoms: A Mega-Analysis From the ENIGMA PTSD Working Group
- Alcohol Use Disorder and Smoking-Associated Molecular Alterations in Human Prefrontal Cortex in Single Nucleus (sn) RNA-Seq
- Single-cell profiling of DNA methylation in autism spectrum disorder prefrontal cortex reveals distinct regulatory and aging signatures
BibTeX
@article{hussain2026lower,
title = {{Lower Gyrification of the Ventromedial Prefrontal Cortex in Posttraumatic Stress Disorder: An ENIGMA-PTSD Study}},
author = {Ahmed Hussain and C. Lexi Baird and Ashley Huggins and Courtney Russell and Delin Sun and Leonel Rangel-Jimenez and Chadi Abdallah and Michael Angstadt and Geoffrey May and Hannah Berg and Jennifer Blackford and Josh Cisler and Judith Daniels and Nicholas Davenport and Richard Davidson and Maria Densmore and Seth Disner and Wissam El-Hage and Amit Etkin and Negar Fani and Jessie Frijling and Evan Gordon and Daniel Grupe and Ryan Herringa and Julia Herzog and David Hofmann and Anna Hudson and Tanja Jovanovic and Anthony King and Saskia B.J. Koch and Ruth Lanius and Amit Lazarov and Gen Li and Israel Liberzon and Shmuel Lissek and Guangming Lu and Antje Manthey and Adi Maron-Katz and Katie Mclaughlin and Sven Mueller and Laura Nawijn and Steven Nelson and Yuval Neria and Richard W.J. Neufeld and Jack Nitschke and Bunmi Olatunji and Miranda Olff and Matthew Peverill and Rongfeng Qi and Yann Quidé and Orren Ravid and Ivan Rektor and Kerry Ressler and Pavel Říha and Marisa Ross and Kelly Sambrook and Christian Schmahl and Anika Sierk and Scott Sponheim and Jennifer Stevens},
journal = {Biological Psychiatry Global Open Science},
year = {2026},
month = nov,
doi = {10.1016/j.bpsgos.2025.100679},
url = {https://inserm.hal.science/inserm-05860919v1},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Lower Gyrification of the Ventromedial Prefrontal Cortex in Posttraumatic Stress Disorder: An ENIGMA-PTSD Study
AU - Ahmed Hussain
AU - C. Lexi Baird
AU - Ashley Huggins
AU - Courtney Russell
AU - Delin Sun
AU - Leonel Rangel-Jimenez
AU - Chadi Abdallah
AU - Michael Angstadt
AU - Geoffrey May
AU - Hannah Berg
AU - Jennifer Blackford
AU - Josh Cisler
AU - Judith Daniels
AU - Nicholas Davenport
AU - Richard Davidson
AU - Maria Densmore
AU - Seth Disner
AU - Wissam El-Hage
AU - Amit Etkin
AU - Negar Fani
AU - Jessie Frijling
AU - Evan Gordon
AU - Daniel Grupe
AU - Ryan Herringa
AU - Julia Herzog
AU - David Hofmann
AU - Anna Hudson
AU - Tanja Jovanovic
AU - Anthony King
AU - Saskia B.J. Koch
AU - Ruth Lanius
AU - Amit Lazarov
AU - Gen Li
AU - Israel Liberzon
AU - Shmuel Lissek
AU - Guangming Lu
AU - Antje Manthey
AU - Adi Maron-Katz
AU - Katie Mclaughlin
AU - Sven Mueller
AU - Laura Nawijn
AU - Steven Nelson
AU - Yuval Neria
AU - Richard W.J. Neufeld
AU - Jack Nitschke
AU - Bunmi Olatunji
AU - Miranda Olff
AU - Matthew Peverill
AU - Rongfeng Qi
AU - Yann Quidé
AU - Orren Ravid
AU - Ivan Rektor
AU - Kerry Ressler
AU - Pavel Říha
AU - Marisa Ross
AU - Kelly Sambrook
AU - Christian Schmahl
AU - Anika Sierk
AU - Scott Sponheim
AU - Jennifer Stevens
PY - 2026
DA - 2026/11/12
JO - Biological Psychiatry Global Open Science
DO - 10.1016/j.bpsgos.2025.100679
UR - https://inserm.hal.science/inserm-05860919v1
AB - 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.
SN - 2667-1743
ER -