Childhood maltreatment is linked to transdiagnostic age- and sex-specific cortical thinning and reduced amygdalar volume in young adults

Childhood maltreatment is a transdiagnostic risk factor, whose distributed neural correlates are most timely and urgently assessed in young adults in the earliest stages of emerging mental disorders. Here, we applied a data-driven multivariate approach to identify distributed brain structural signatures associated with childhood maltreatment, with a particular focus on limbic regions, and to examine their relevance for later functional outcomes. In a transdiagnostic sample of 251 individuals (mean age 24.9 ± 4.3, 51.8% male) with early affective or anxiety syndromes, we used a multivariate sparse partial least squares algorithm to investigate multi-layered associations between grey-matter volume and the Childhood Trauma Questionnaire. We identified signatures linking age-dependent physical abuse and minimization/denial to widespread cortical thinning ( ρ =0.424, p =.007; R 2 = 18%), as well as female-specific emotional abuse to smaller left amygdala nuclei ( ρ =0.566, p =.014; R 2 = 32% shared variance). In females, emotional abuse predicted poorer functioning at 1- ( β =-0.45, p <.001) and 2-year ( β =-0.48, p <.001) follow-up, while smaller amygdala nuclei predicted better outcomes at 2 years ( β =0.26, p =.04), although sensitive to including baseline functioning ( β =0.17, p =.071). Support-vector machine (SVM) analyses further showed that females with higher trauma-related loadings and larger left amygdala nuclei could be identified using clinical features, although only in the extreme tertile split ( BAC =69.2%, p =.038, AUC =0.62, 95%- CI= 0.40–0.84). These findings suggest that trauma-reactive amygdala alterations may reflect heterogeneous sex-specific adaptation trajectories. This highlights the potential of age-, sex-, and trauma type-sensitive assessment at the earliest point of care, and proposes that early identification of such neurobiological signatures can inform more individualised approaches to treatment and recovery.

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Journal
European Neuropsychopharmacology
Published
2026-06-09
DOI
https://doi.org/10.1016/j.euroneuro.2026.112900
Primary Topic
Child Abuse and Related Trauma
Type
article
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article

Childhood maltreatment is linked to transdiagnostic age- and sex-specific cortical thinning and reduced amygdalar volume in young adults

Vera Flasbeck, Christoph Mulert, Pavol Mikoláš, Karolina Leopold et al.
European Neuropsychopharmacology
Child Abuse and Related Trauma
article

Childhood maltreatment is linked to transdiagnostic age- and sex-specific cortical thinning and reduced amygdalar volume in young adults

Vera Flasbeck, Christoph Mulert, Pavol Mikoláš, Karolina Leopold, Falk Gerrik Verhees, Christina Berndt, Philipp Ritter, David Popovic, Leonardo Tozzi, Jana Fiebig, Clara Vetter, Julia Martini, Gregor Leicht, Birgit Maicher, Stefanie Schreiter, Eva Mennigen, Andreas J. Fallgatter, Felix Bermpohl, Andrea Pfennig, Irina Falkenberg, Fabian Huth, Vivien Kraft, Clara Weyer, Paris Alexandros Lalousis, Anne Rau, Georg Juckel, Nikolaos Koutsouleris, Andreas Jansen, Andreas Reif, Paula M. Henneberg, Martin Lambert, Christoph U. Correll, Florian Thomas-Odenthal, Thomas Stamm, Andreas Bechdolf, Peter Falkai, Udo Dannlowski, Silke Matura, Michael Bauer, Tilo Kircher, Thomas Ethofer, Kyra Bröckel-Bundt
article en

Abstract

Childhood maltreatment is a transdiagnostic risk factor, whose distributed neural correlates are most timely and urgently assessed in young adults in the earliest stages of emerging mental disorders. Here, we applied a data-driven multivariate approach to identify distributed brain structural signatures associated with childhood maltreatment, with a particular focus on limbic regions, and to examine their relevance for later functional outcomes. In a transdiagnostic sample of 251 individuals (mean age 24.9 ± 4.3, 51.8% male) with early affective or anxiety syndromes, we used a multivariate sparse partial least squares algorithm to investigate multi-layered associations between grey-matter volume and the Childhood Trauma Questionnaire. We identified signatures linking age-dependent physical abuse and minimization/denial to widespread cortical thinning ( ρ =0.424, p =.007; R 2 = 18%), as well as female-specific emotional abuse to smaller left amygdala nuclei ( ρ =0.566, p =.014; R 2 = 32% shared variance). In females, emotional abuse predicted poorer functioning at 1- ( β =-0.45, p <.001) and 2-year ( β =-0.48, p <.001) follow-up, while smaller amygdala nuclei predicted better outcomes at 2 years ( β =0.26, p =.04), although sensitive to including baseline functioning ( β =0.17, p =.071). Support-vector machine (SVM) analyses further showed that females with higher trauma-related loadings and larger left amygdala nuclei could be identified using clinical features, although only in the extreme tertile split ( BAC =69.2%, p =.038, AUC =0.62, 95%- CI= 0.40–0.84). These findings suggest that trauma-reactive amygdala alterations may reflect heterogeneous sex-specific adaptation trajectories. This highlights the potential of age-, sex-, and trauma type-sensitive assessment at the earliest point of care, and proposes that early identification of such neurobiological signatures can inform more individualised approaches to treatment and recovery.

European NeuropsychopharmacologyVol. 112
Goethe University Frankfurt (DE), Universität Hamburg (DE), Philipps University of Marburg (DE), King's College London (GB), Justus-Liebig-Universität Gießen (DE), University Hospital Münster (DE), Fraunhofer Institute for Translational Medicine and Pharmacology (DE), University Medical Center Hamburg-Eppendorf (DE), Vivantes Klinikum (DE), German Centre for Cardiovascular Research (DE), Jena University Hospital (DE), Medizinische Hochschule Brandenburg Theodor Fontane (DE), STZ eyetrial (DE), Max Planck Institute of Psychiatry (DE), Klinikum im Friedrichshain (DE), LWL-Universitätsklinikum Bochum (DE), University Hospital Carl Gustav Carus (DE), Technische Universität Dresden (DE), Charité - Universitätsmedizin Berlin (DE), University of Tübingen (DE), Ludwig-Maximilians-Universität München (DE), Ruhr University Bochum (DE), Stanford University (US)
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Child Abuse and Related Trauma
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