The non-specific nature of mental health and structural brain outcomes following childhood trauma

Theresa K. Haidl*, Dennis M. Hedderich, Marlene Rosen, Nathalie Kaiser, Mauro Seves, Thorsten Lichtenstein, Nora Penzel, Julian Wenzel, Lana Kambeitz-ilankovic, Anne Ruef, David Popovic, Frauke Schultze-lutter, Katharine Chisholm, Rachel Upthegrove, Raimo K. R. Salokangas, Christos Pantelis, Eva Meisenzahl, Stephen J. Wood, Paolo Brambilla, Stefan BorgwardtStephan Ruhrmann, Joseph Kambeitz, Nikolaos Koutsouleris

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


Background: Childhood trauma (CT) is associated with an increased risk of mental health disorders; however, it is unknown whether this represents a diagnosis-specific risk factor for specific psychopathology mediated by structural brain changes. Our aim was to explore whether (i) a predictive CT pattern for transdiagnostic psychopathology exists, and whether (ii) CT can differentiate between distinct diagnosis-dependent psychopathology. Furthermore, we aimed to identify the association between CT, psychopathology and brain structure.

Methods: We used multivariate pattern analysis in data from 643 participants of the Personalised Prognostic Tools for Early Psychosis Management study (PRONIA), including healthy controls (HC), recent onset psychosis (ROP), recent onset depression (ROD), and patients clinically at high-risk for psychosis (CHR). Participants completed structured interviews and self-report measures including the Childhood Trauma Questionnaire, SCID diagnostic interview, BDI-II, PANSS, Schizophrenia Proneness Instrument, Structured Interview for Prodromal Symptoms and structural MRI, analyzed by voxel-based morphometry.

Results: (i) Patients and HC could be distinguished by their CT pattern with a reasonable precision [balanced accuracy of 71.2% (sensitivity = 72.1%, specificity = 70.4%, p ≤ 0.001]. (ii) Subdomains 'emotional neglect' and 'emotional abuse' were most predictive for CHR and ROP, while in ROD 'physical abuse' and 'sexual abuse' were most important. The CT pattern was significantly associated with the severity of depressive symptoms in ROD, ROP, and CHR, as well as with the PANSS total and negative domain scores in the CHR patients. No associations between group-separating CT patterns and brain structure were found.

Conclusions: These results indicate that CT poses a transdiagnostic risk factor for mental health disorders, possibly related to depressive symptoms. While differences in the quality of CT exposure exist, diagnostic differentiation was not possible suggesting a multi-factorial pathogenesis.
Original languageEnglish
Pages (from-to)1005-1014
Number of pages10
JournalPsychological Medicine
Issue number3
Early online date6 Jul 2021
Publication statusPublished - 6 Feb 2023

Bibliographical note

Copyright © The Author(s), 2021. Published by Cambridge University Press.

Funding: PRONIA is a Collaborative Project funded by the European Union under the 7th Framework Programme under grant agreement n° 602152. R.U. reports grants from Medical Research Council, grants from the National Institute for Health Research, and personal fees from Sunovion, outside the submitted work. N.K. and R.S. received honoraria for talks presented at education meetings organized by Otsuka/Lundbeck. C.P. participated in advisory boards for Janssen-Cilag, AstraZeneca, Lundbeck, and Servier and received honoraria for talks presented at educational meetings organized by AstraZeneca, Janssen-Cilag, Eli Lilly, Pfizer, Lundbeck, and Shire. C.P. acknowledges support by an Australian National Health & Medical Research Council (NHMRC) Senior Principal Research Fellowship (ID: 1105825), an NHMRC Program Grant (ID: 1150083). J.K. reports funding by the DFG (KA 4413/1-1) and received honoraria for talks presented at educational meetings organized by Janssen and Otsuka/Lundbeck.


  • Brain structure
  • childhood maltreatment
  • emotional abuse
  • emotional neglect
  • multivariate pattern analysis
  • physical abuse
  • sexual abuse


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