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Wiegert, J.* ; Marty-Lombardi, S.* ; Oweda, J.* ; Lenz, E.* ; Ahnert, P.* ; Berger, K.* ; Brenner, H.* ; Frank, J.* ; Grabe, H.J.* ; Greiser, K.H.* ; Klinger-König, J.* ; Karch, A.* ; Leitzmann, M.* ; Meinke‐Franze, C.* ; Mikolajczyk, R.* ; Nees, F.* ; Niendorf, T.* ; Sander, O.* ; Schmidt, C.O.* ; Riedel‐Heller, S.G.* ; Ritter, K.* ; Peters, A. ; Pischon, T.* ; Witt, S.H.* ; Nitsche, J.* ; Naamanka, J.* ; Volkmer, S.* ; Mai, A.* ; Abas, A.* ; Li, X.* ; Meyer-Lindenberg, A.* ; Gradinger, T.* ; Streit, F.* ; Braun, U.* ; Schwarz, E.*

Breaking the norm: Population-scale deviations of brain structure in depression and anxiety.

Mol. Psychiatry, DOI: 10.1038/s41380-026-03691-4 (2026)
Publ. Version/Full Text Research data DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
Structural brain alterations associated with depression and anxiety are subtle, heterogeneous, and difficult to characterize. We applied autoencoder-based normative modeling to contrastively learned structural MRI representations from two large population-based cohorts (German National Cohort, N ≈ 29,000; UK Biobank, N ≈ 25,000) to quantify individual deviations from normative brain structure across symptom dimensions of depression, anxiety, and, for contextualization, alcohol use.Deviation magnitude increased with symptom severity for depressive and anxiety symptoms and was most pronounced in individuals with high alcohol use. Directional analyses revealed shared deviation patterns for depression and anxiety that were largely distinct from alcohol-related deviations, and these patterns generalized across cohorts. These affective-symptom-related patterns implicated distributed regional brain-structural variation. Individual deviation profiles improved classification of symptomatic status beyond demographic covariates, with gains concentrated at higher symptom severity.Together, these findings indicate that affective symptoms are associated with reproducible, dimensional patterns of regional brain-structural deviation that extend beyond normative population variability, supporting transdiagnostic models of internalizing psychopathology.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Normative ; Anxiety ; Depression (economics) ; Absolute Deviation ; Structural Equation Modeling ; Population ; Alcohol Consumption; Gray-matter Abnormalities; Alcohol-consumption; Disorder
ISSN (print) / ISBN 1359-4184
e-ISSN 1476-5578
Journal Molecular Psychiatry
Publisher Springer
Publishing Place The Campus, 4 Crinan St, London, N1 9xw, England
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology (EPI)
Grants The project was supported by the DZPG (German Centre for Mental Health Research) and by the BMBF (German Ministry of Education and Research) grant 01EE2303E. This work was supported by the Hector foundation II.