Network-level structural alterations distinguish persistent from remitted post-traumatic stress disorder: a morphometric covariance approach

Background: Post-traumatic stress disorder (PTSD) exhibits heterogeneous clinical trajectories: while many affected individuals achieve remission, a substantial proportion develop a chronic, persistent form. The neuroanatomical mechanisms distinguishing these divergent outcomes remain poorly defined. This study aimed to elucidate the structural network organisation of persistent PTSD using structural covariance network analysis. Methods: Participants included trauma-unexposed healthy controls (HC; n = 112), individuals with remitted PTSD (n = 32), and those with persistent PTSD (n = 78). High-resolution T1-weighted magnetic resonance imaging data were analyzed using independent component analysis to extract spatially independent morphometric networks. Gray matter volumes within these networks were subsequently compared across groups. Results: Linear trend analysis revealed a stepwise reduction in gray matter volume within the frontal-cognitive control and visual networks across groups (HC > remitted PTSD > persistent PTSD). Further examination of inter-network connectivity demonstrated heightened connectivity between the frontal-cognitive control and temporo-insular-limbic networks in the persistent PTSD group, compared with both the remitted PTSD and HC groups. Notably, the remitted PTSD group exhibited inter-network connectivity levels comparable to those of HC. This hyperconnectivity in persistent PTSD reflects compensatory recruitment of cognitive control mechanisms to regulate interoceptive and emotional processing systems, thereby sustaining symptom modulation. Conclusion: Persistent PTSD is characterised by progressive gray matter volume reductions and compensatory hyperconnectivity between cognitive control and limbic-interoceptive networks, indicative of sustained engagement of regulatory mechanisms to modulate enduring symptoms. These findings provide novel neurobiological insights into the mechanisms of PTSD chronicity and highlight potential network-level targets (particularly prefrontal-limbic interactions) for future investigation of personalised interventions in treatment-resistant cases.