Characterising a stress-sensitive default mode network (DMN) deficit in major psychiatric disorders

Commun Biol. 2026 Feb 25. doi: 10.1038/s42003-025-09400-1. Online ahead of print.

ABSTRACT

Childhood trauma (CT) is associated with cognitive impairment across major psychiatric disorders. We tested a novel transdiagnostic hypothesis that atypical connectivity of the default mode network (DMN) mediates the association between childhood trauma (CT) and cognitive impairment. The sample of 1851 individuals aged 18-25 included 433 patients with depression, eating disorders, alcohol use disorder, psychosis and ADHD) and were recruited as part of the ESTRA/STRATIFY/IMAGEN studies. CT was measured using the Childhood Trauma Questionnaire (CTQ). The CANTAB spatial working memory task was administered to assess cognition. Four a priori seeds of the default mode network (DMN) were measured during face processing, namely the medial prefrontal cortex (PFC), right lateral parietal (LP), left lateral parietal (LP) and posterior cingulate cortex (PCC), according to the Harvard-Oxford Cortical and Subcortical Atlas (http://www.cma.mgh.harvard.edu/fsl_atlas.html) as implemented in CONN. Patients had significantly reduced DMN connectivity between the four chosen DMN seeds and the rest of the brain. Reduced DMN connectivity mediated the association between higher CT and worse cognitive performance. Our findings are transdiagnostic in nature with stronger effects in some regions observed in depression, and suggest one transdiagnostic cortical network via which CT's effects on cognition are transmitted.

PMID:41741790 | DOI:10.1038/s42003-025-09400-1