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

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.

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Journal
Communications Biology
Published
2026-02-25
DOI
https://doi.org/10.1038/s42003-025-09400-1
Primary Topic
Functional Brain Connectivity Studies
Type
article
Field-Weighted Citation Impact
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article

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

Betteke Maria van Noort, Sinéad King, Julia Sinclair, Marina Bobou et al.
Communications Biology
Functional Brain Connectivity Studies
article

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

Betteke Maria van Noort, Sinéad King, Julia Sinclair, Marina Bobou, David D. Cotter, E. Artiges, Nick Ortiz, Hugh P. Garavan, Rüdiger Brühl, Gary Donohoe, Zuo Zhang, Luise Poustka, Yuning Zhang, Allan H. Young, Robert Whelan, Marie-Laure Paillère Martinot, Michael N. Smolka, Sylvane Desrivières, Eric Wolsztynski, Henrik Walter, Gareth J. Barker, Lauren Robinson, Tobias Banaschewski, Andreas Heinz, Sarah Hohmann, Gunter Schumann, Nilakshi Vaidya, Christian Baeuchl, M. John Broulidakis, Ulrike Schmidt, Herta Flor, Penny Gowland, Arun L. W. Bokde, Nathalie Holz, Jeanne Winterer, Argyris Stringaris, Jean-Luc Martinot
article en

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.

Communications Biology
University of Vermont (US), Physikalisch-Technische Bundesanstalt (DE), Northeastern University (US), Centre National de la Recherche Scientifique (FR), University of Nottingham (GB), Royal College of Surgeons in Ireland (IE), Inserm (FR), University of Mannheim (DE), King's College London (GB), Ollscoil na Gaillimhe – University of Galway (IE), South London and Maudsley NHS Foundation Trust (GB), Université Paris Cité (FR), Trinity College Dublin (IE), Heidelberg University (DE), Fudan University (CN), Commissariat à l'Énergie Atomique et aux Énergies Alternatives (FR), University College Cork (IE), Université Paris-Saclay (FR), University Hospital Heidelberg (DE), Humboldt-Universität zu Berlin (DE), Sorbonne Université (FR), MSB Medical School Berlin (DE), Assistance Publique – Hôpitaux de Paris (FR), Central Institute of Mental Health (DE), German Center for Infection Research (DE), Pitié-Salpêtrière Hospital (FR), CEA Paris-Saclay (FR), Laboratoire de Biologie et Pharmacologie Appliquée (FR), Shanghai Center for Brain Science and Brain-Inspired Technology (CN), University of Southampton (GB), University College London (GB), Imperial College London (GB), Freie Universität Berlin (DE), Technische Universität Dresden (DE), Charité - Universitätsmedizin Berlin (DE), University of Birmingham (GB), Ludwig-Maximilians-Universität München (DE)
European Commission, Science Foundation Ireland, European Regional Development Fund, H2020 Marie Skłodowska-Curie Actions
Openalex Percentile: Top 47%
Functional Brain Connectivity Studies
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