Gray matter correlates of childhood maltreatment lack replicability in a multi-cohort brain-wide association study

Janik Goltermann (), Nils R. Winter, Susanne Meinert, Dominik Grotegerd, Anna Kraus, Kira Flinkenflügel, Luisa Altegoer, Judith Krieger, Elisabeth J. Leehr, Joscha Böhnlein, Linda M. Bonnekoh, Maike Richter, Tim Hahn, Lukas Fisch, Marius Gruber, Marco Hermesdorf, Klaus Berger, Volker Arolt, Katharina Brosch, Frederike Stein, Florian Thomas-Odenthal, Paula Usemann, Lea Teutenberg, Vincent Hammes, Hamidreza Jamalabadi, Nina Alexander, Benjamin Straube, Andreas Jansen, Igor Nenadić, Tilo Kircher, Nils Opel and Udo Dannlowski
Additional contact information
Janik Goltermann: University of Münster
Nils R. Winter: University of Münster
Susanne Meinert: University of Münster
Dominik Grotegerd: University of Münster
Anna Kraus: University of Münster
Kira Flinkenflügel: University of Münster
Luisa Altegoer: University of Münster
Judith Krieger: University of Münster
Elisabeth J. Leehr: University of Münster
Joscha Böhnlein: University of Münster
Linda M. Bonnekoh: University of Münster
Maike Richter: University of Münster
Tim Hahn: University of Münster
Lukas Fisch: University of Münster
Marius Gruber: University of Münster
Marco Hermesdorf: University of Münster
Klaus Berger: University of Münster
Volker Arolt: University of Münster
Katharina Brosch: University of Marburg
Frederike Stein: University of Marburg
Florian Thomas-Odenthal: University of Marburg
Paula Usemann: University of Marburg
Lea Teutenberg: University of Marburg
Vincent Hammes: University of Marburg
Hamidreza Jamalabadi: University of Marburg
Nina Alexander: University of Marburg
Benjamin Straube: University of Marburg
Andreas Jansen: University of Marburg
Igor Nenadić: University of Marburg
Tilo Kircher: University of Marburg
Nils Opel: Charité–Universitätsmedizin Berlin
Udo Dannlowski: University of Münster

Nature Communications, 2025, vol. 16, issue 1, 1-14

Abstract: Abstract Childhood maltreatment effects on cerebral gray matter have been frequently discussed as a neurobiological pathway for depression. However, localizations are highly heterogeneous, and recent reports have questioned the replicability of mental health neuroimaging findings. Here, we investigate the replicability of gray matter correlates of maltreatment, measured retrospectively via the Childhood Trauma Questionnaire, across three large adult cohorts (total N = 3225). Pooling cohorts yields maltreatment-related gray matter reductions, with most extensive effects when not controlling for depression diagnosis (maximum partial R2 = .022). However, none of these effects significantly replicate across cohorts. Non-replicability is consistent across a variety of maltreatment subtypes and operationalizations, as well as subgroup analyses with and without depression, and stratified by sex. Results are furthermore consistent across a variety of gray matter operationalizations, including voxel-based morphometry and parcellation-based cortical and subcortical measures. In this work, we show that there is little evidence for the replicability of gray matter correlates of childhood maltreatment, when adequately controlling for psychopathology. This underscores the need to focus on replicability research in mental health neuroimaging.

Date: 2025
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DOI: 10.1038/s41467-025-62374-w

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