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Interactive impact of childhood maltreatment, depression, and age on cortical brain structure: mega-analytic findings from a large multi-site cohort

  • Leonardo Tozzi (a1) (a2), Lisa Garczarek (a1), Deborah Janowitz (a3), Dan J. Stein (a4), Katharina Wittfeld (a3) (a5), Henrik Dobrowolny (a1), Jim Lagopoulos (a6) (a7), Sean N. Hatton (a6), Ian B. Hickie (a6), Angela Carballedo (a8), Samantha J. Brooks (a4) (a9), Daniella Vuletic (a4), Anne Uhlmann (a4) (a10), Ilya M. Veer (a11), Henrik Walter (a11), Robin Bülow (a12), Henry Völzke (a13), Johanna Klinger-König (a3), Knut Schnell (a14) (a15) (a16), Dieter Schoepf (a17), Dominik Grotegerd (a18), Nils Opel (a18), Udo Dannlowski (a18), Harald Kugel (a19), Elisabeth Schramm (a20) (a21), Carsten Konrad (a22) (a23), Tilo Kircher (a23), Dilara Jüksel (a23), Igor Nenadić (a23), Axel Krug (a23), Tim Hahn (a18), Olaf Steinsträter (a23) (a24), Ronny Redlich (a18), Dario Zaremba (a18), Bartosz Zurowski (a25), Cynthia H.Y. Fu (a26) (a27), Danai Dima (a28) (a29), James Cole (a28), Hans J. Grabe (a3), Colm G. Connolly (a30) (a31), Tony T. Yang (a30) (a32), Tiffany C. Ho (a30) (a33), Kaja Z. LeWinn (a30) (a32), Meng Li (a34), Nynke A. Groenewold (a4), Lauren E. Salminen (a35), Martin Walter (a1) (a34) (a36), Alan N Simmons (a37) (a38), Theo G.M. van Erp (a39), Neda Jahanshad (a35), Bernhard T. Baune (a18) (a40) (a41) (a42), Nic J.A. van der Wee (a43), Marie-Jose van Tol (a44), Brenda W.J.H. Penninx (a45), Derrek P. Hibar (a39), Paul M. Thompson (a35), Dick J. Veltman (a45), Lianne Schmaal (a46) (a47), Thomas Frodl (a1) (a6) (a48) and ‘for the ENIGMA-MDD Consortium’ (a1) (a2) (a3) (a4) (a5) (a6) (a7) (a8) (a9) (a10) (a11) (a12) (a13) (a14) (a15) (a16) (a17) (a18) (a19) (a20) (a21) (a22) (a23) (a24) (a25) (a26) (a27) (a28) (a29) (a30) (a31) (a32) (a33) (a34) (a35) (a36) (a37) (a38) (a39) (a40) (a41) (a42) (a43) (a44) (a45) (a46) (a47) (a48)...



Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age.


Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer.


CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions.


Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.


Corresponding author

Author for correspondence: Thomas Frodl, E-mail:


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