Decomposing neuroanatomical heterogeneity in depression: insights from an ENIGMA major depressive disorder working group study in 5146 individuals

L Sempach; S Ulrich; SEEC Bauduin; J Bauer; F Benedetti; K Berger; B Besteher; R Bülow; CG Connolly; E Corruble; B Couvy-Duchesne; KR Cullen; U Dannlowski; CG Davey; D Dima; A Dols; JW Evans; C Fu; P Fuentes-Claramonte; AS Gonul; IH Gotlib; R Goya-Maldonado; HJ Grabe; NA Groenewold; D Grotegerd; O Gruber; T Hahn; JP Hamilton; LKM Han; BJ Harrison; SN Hatton; M Hermesdorf; IB Hickie; TC Ho; JM Hubbert; N Jahanshad; H Jamalabadi; AJ Jamieson; C Jurischka; A Jüllig; T Kamishikiryo; T Kircher; SM Koopowitz; B Krämer; A Kraus; J Krieger; A Krug; J Lagopoulos; M Li; A McIntosh; S Meinert; EMT Melloni; B Mwangi; I Nenadic; A Ojha; G Okada; ML Oudega; BWJH Penninx; S Poletti; E Pomarol-Clotet; MJ Portella; L Reneman; E Rodriguez-Cano; M Sacchet; R Salvador; A Schrantee; H Shinzato; K Sim; TM Slump; JC Soares; DJ Stein; F Stein; L Teutenberg; F Thomas-Odenthal; SI Thomopoulos; NJA van der Wee; SJA van der Werff; H Völzke; M Walter; HC Whalley; S Whittle; K Wittfeld; MJ Wu; TT Yang; C Zarate; GB Zunta-Soares; PM Thompson; DJ Veltman; E Pozzi; L Schmaal; A Schmidt

Journal article

Decomposing neuroanatomical heterogeneity in depression: insights from an ENIGMA major depressive disorder working group study in 5146 individuals

L Sempach, S Ulrich, SEEC Bauduin, J Bauer, F Benedetti, K Berger, B Besteher, R Bülow, CG Connolly, E Corruble, B Couvy-Duchesne, KR Cullen, U Dannlowski, CG Davey, D Dima, A Dols, JW Evans, C Fu, P Fuentes-Claramonte, AS Gonul Show all

Translational Psychiatry | Published : 2026

DOI: 10.1038/s41398-026-04189-x

Open access

Abstract

The clinical and biological heterogeneity of major depressive disorder (MDD) may reflect the aggregation of different conditions with distinct pathologies under a single diagnostic label. Neuroanatomical heterogeneity in MDD was examined using a harmonized, age- and sex-matched sample from the ENIGMA MDD consortium (N = 5146; age range: 9–82 years; 64% female). Analyses of global neurostrucutral variability revealed greater cortical thickness heterogeneity in MDD compared with healthy controls (Cohen’s d = –0.26). Regionally, increased variability in cortical thickness was most prominent in the cingulate (+6.1 to +6.6% more variation in MDD) and insular (+5.8%) cortices, as well as in the fr..

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