Structural covariance of early visual cortex is negatively associated with PTSD symptoms: A Mega-Analysis from the ENIGMA PTSD workgroup

Background: Identifying robust neural signatures of posttraumatic stress disorder (PTSD) symptoms is important to facilitate precision psychiatry and help in understanding and treatment of the disorder. Emergent research suggests structural covariance of early visual regions is associated with later PTSD development. However, large-scale analyses are needed - in heterogeneous samples of trauma-exposed and trauma naive individuals - to determine if such a neural signature is a robust - and potentially a pretrauma - marker of vulnerability. Methods: We analyzed data from the ENIGMA-PTSD dataset (n = 2,814) and the Human Connectome Project - Young Adult (HCP-YA) dataset (n = 890) to investigate whether structural covariance of early visual cortex is associated with either PTSD symptoms or perceived stress. Structural covariance was derived from a multimodal pattern previously identified in recent trauma survivors, and participant loadings on the profile were included in linear mixed effects models to evaluate associations with stress. Results: Early visual cortex covariance loadings were negatively associated with PTSD symptoms in the ENIGMA-PTSD dataset. The relationship persisted when accounting for prior childhood maltreatment; supporting PTSD symptom specificity, no relationship was observed with depressive symptoms and no association was observed between loadings and perceived stress measures in the HCP-YA dataset. Conclusion: Structural covariance of early visual cortex was robustly associated with PTSD symptoms across an international, heterogeneous sample of trauma survivors. Future studies should aim to identify specific mechanisms that underlie structural alterations in the visual cortex to better understand posttrauma psychopathology.