Early posttrauma disruptions within default mode network connectivity predict PTSD symptom trajectories: evidence from a longitudinal mega-analysis.

Abstract

Posttraumatic stress disorder (PTSD) is a chronic psychiatric disorder associated with functional impairment and health burden. Evidence highlights the role of large-scale neural network disruptions, within and between the Default Mode Network (DMN) and Salience Network (SN), in PTSD pathophysiology, and early alterations in these networks may serve as biomarkers for predicting PTSD symptom trajectories and guiding early interventions. This longitudinal mega-analysis integrated resting-state functional connectivity (rsFC) data from two trauma-exposed cohorts (Tel Aviv and Toledo), collected within the first month posttrauma. Seed-based rsFC analyses focused on DMN regions (hippocampus, ventromedial prefrontal cortex [vmPFC], posterior cingulate cortex) and SN regions (amygdala, insula, dorsal anterior cingulate cortex [dACC]). PTSD symptoms were assessed at 12- to 14-month follow-up using the Clinician-Administered PTSD Scale (CAPS-5) and PTSD Checklist (PCL-5). Early posttrauma reductions in within-DMN connectivity, particularly between the hippocampus and rostral ACC/vmPFC, mPFC, and inferior parietal lobe, were associated with greater PTSD symptom severity at annual follow-up. Decreased connectivity between the DMN and visual cortex (calcarine) was also linked to more severe symptoms. Decreased DMN-SN connectivity, specifically between the amygdala and rostral ACC/vmPFC, was linked to more severe symptoms at follow-up, adding to a complex picture of the relationship between networks. Early disruptions in within-DMN connectivity emerged as the most consistent neural correlate of later PTSD symptom severity. These findings underscore a central role of within-DMN dysfunction in PTSD pathophysiology, reflecting deficits in context processing governed by hippocampus-mPFC circuitry. Identifying these early neural markers may guide targeted interventions to prevent chronic PTSD.