Journal Article

FZJ-2026-05924

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png 340. Common Cortical Patterns Shape Variability Within and Overlap Across Psychiatric Disorders – A Transdiagnostic ENIGMA Study

Hettwer, M. (Corresponding author)FZJ* ; Saberi, A.FZJ* ; Shafiei, G. ; de Boer, A. A. ; van den Heuvel, O. A. ; Schmaal, L. ; Pozzi, E. ; Andreassen, O. A. ; Ching, C. R. ; Buitelaar, J. ; Lawrence, K. E. ; Turner, J. ; van Erp, T. G. ; Stein, D. J. ; Pine, D. S. ; Winkler, A. ; van der Wee, N. ; Groenewold, N. A. ; Bas-Hoogendam, J. M. ; Bernhardt, B. C. ; Thompson, P. M. ; Eickhoff, S. B.FZJ* ; Kirschner, M. ; Satterthwaite, T. ; Valk, S. L.FZJ*

2026
Elsevier Science Amsterdam [u.a.]

This record in other databases:  

Please use a persistent id in citations: doi:10.1016/j.biopsych.2026.03.574

Abstract: BackgroundMental disorders show pronounced phenotypic heterogeneity within diagnoses and overlap across them, limiting the ability of group-level studies to identify distinct brain correlates. Large, transdiagnostic samples and individualized approaches are therefore needed to reveal systematic patterns that underlie variability and overlap in psychiatric brain alterations.MethodsIn a global collaborative effort, we analyzed region-wise, in vivo cortical thickness (CT) estimates from 10,188 patients (schizophrenia, generalized anxiety, autism spectrum, bipolar, obsessive-compulsive, and major depressive disorders) and 12,251 controls (5-80 years old). Using normative modeling, we quantified each individual’s CT deviations from a reference cohort. Principal component analysis identified the dominant cortical axes capturing shared patterns of structural deviation. We then examined how within-disorder variability, co-occurring extreme deviations, and between-disorder overlap align with these axes.ResultsCT deviations were organized along two normative axes: one spanning paralimbic to heteromodal cortex, and another spanning unimodal to heteromodal/paralimbic cortex. Variability within disorders was largely differentiated along the unimodal-to-heteromodal axis. Extreme deviations (z >1.96/ <-1.06) were highly heterogeneous, but co-occured in regions that were more strongly connected to each other, with hubs in the heteromodal cortex. Transdiagnostic overlap was high (84–95%) overall, peaking in the paralimbic cortex and progressively decreasing toward heteromodal regions. Findings were robust to leave-one-disorder-out analyses.ConclusionsUsing one of the largest psychiatric imaging samples to date, we show that CT deviations follow two cortical axes capturing within-disorder variability and transdiagnostic overlap. Convergence along these axes may shape phenotypic similarities across individuals and highlights the value of a systems-level, lifespan perspective when interpreting disorder-related alterations.KeywordsTransdiagnostic psychiatry, ENIGMA, Cortical Thickness, cortical gradient

---

Contributing Institute(s):

1. Gehirn & Verhalten (INM-7)

Research Program(s):

1. 5251 - Multilevel Brain Organization and Variability (POF4-525) (POF4-525)

Appears in the scientific report 2026

---

Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 10 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

---