Cover Image

A longitudinal DNA methylation atlas and its link to brain structure and mental health

Epigenetic mechanisms are thought to contribute to neurodevelopmental vulnerability for psychiatric disorders, yet longitudinal evidence linking DNA methylation (DNAm) to brain maturation and psychopathology is limited. Using epigenome-wide DNAm (372,582 CpGs) and whole-brain structural MRI data fro...

Full description

Saved in:
Bibliographic Details
Main Authors: Chen, Di (Author) , Yu, Xinyang (Author) , Cheng, Wei (Author) , Wang, Linbo (Author) , Xiang, Shitong (Author) , Zhang, Wei (Author) , Banaschewski, Tobias (Author) , Bokde, Arun L. W. (Author) , Flor, Herta (Author) , Grigis, Antoine (Author) , Garavan, Hugh (Author) , Gowland, Penny (Author) , Heinz, Andreas (Author) , Brühl, Rüdiger (Author) , Martinot, Jean-Luc (Author) , Paillère Martinot, Marie-Laure (Author) , Artiges, Eric (Author) , Nees, Frauke (Author) , Orfanos, Dimitri Papadopoulos (Author) , Lemaître, Hervé (Author) , Paus, Tomáš (Author) , Poustka, Luise (Author) , Hohmann, Sarah (Author) , Holz, Nathalie E. (Author) , Bäuchl, Christian (Author) , Smolka, Michael N. (Author) , Vaidya, Nilakshi (Author) , Walter, Henrik (Author) , Whelan, Robert (Author) , Feng, Jianfeng (Author) , Thompson, Paul M. (Author) , Schumann, Gunter (Author) , Jia, Tianye (Author) , Desrivières, Sylvane (Author)
Format: Article (Journal)
Language:English
Published: 31 March 2026
In: Molecular psychiatry
Year: 2026, Pages: 1-15
ISSN:1476-5578
DOI:10.1038/s41380-026-03554-y
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41380-026-03554-y
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41380-026-03554-y
Get full text
Author Notes:Di Chen, Xinyang Yu, Wei Cheng, Linbo Wang, Shitong Xiang, Wei Zhang, Tobias Banaschewski, Arun L.W. Bokde, Herta Flor, Antoine Grigis, Hugh Garavan, Penny Gowland, Andreas Heinz, Rüdiger Brühl, Jean-Luc Martinot, Marie-Laure Paillère Martinot, Eric Artiges, Frauke Nees, Dimitri Papadopoulos Orfanos, Hervé Lemaître, Tomáš Paus, Luise Poustka, Sarah Hohmann, Nathalie Holz, Christian Bäuchl, Michael N. Smolka, Nilakshi Vaidya, Henrik Walter, Robert Whelan, Jianfeng Feng, Paul M. Thompson, Gunter Schumann, Tianye Jia, Sylvane Desrivières, on behalf of the IMAGEN Consortium and on behalf of the ENIGMA Epigenetics Working Group
Description
Summary:Epigenetic mechanisms are thought to contribute to neurodevelopmental vulnerability for psychiatric disorders, yet longitudinal evidence linking DNA methylation (DNAm) to brain maturation and psychopathology is limited. Using epigenome-wide DNAm (372,582 CpGs) and whole-brain structural MRI data from the IMAGEN cohort (n = 506, ages 14-19), we identified 18 co-regulated DNAm clusters, ten enriched for brain-expressed genes involved in neuronal development and signalling. The clusters showed consistent longitudinal change and were reproducible in independent adult samples (PPMI, n = 513; ADNI, n = 606). Multivariate analyses revealed coordinated coupling between DNAm change and cortical-subcortical maturation, such that greater DNAm reductions in brain-related clusters associated with greater cortical thinning and subcortical volume changes in the fronto-limbic-striatal axis. Increases in depressive symptoms, and frequency of cannabis use and binge drinking were linked to DNAm changes, with mediation models supporting DNAm as a mechanistic bridge between behaviour and brain change. Two clusters (C1 and C7) were associated with depressive and negative psychotic symptoms across adolescence. Associations of these clusters with depressive symptoms replicated in the PPMI dataset. Their coupling with amygdala-striatal maturation suggests that these DNAm signatures index environmentally shaped affective-motivational neurodevelopment.
Item Description:Gesehen am 14.04.2026
Physical Description:Online Resource
ISSN:1476-5578
DOI:10.1038/s41380-026-03554-y

Similar Items