Cortical profiles of numerous psychiatric disorders and normal development share a common pattern

Molecular psychiatry

Mol Psychiatry. 2022 Nov 15. doi: 10.1038/s41380-022-01855-6. Online ahead of print.


The neurobiological bases of the association between development and psychopathology remain poorly understood. Here, we identify a shared spatial pattern of cortical thickness (CT) in normative development and several psychiatric and neurological disorders. Principal component analysis (PCA) was applied to CT of 68 regions in the Desikan-Killiany atlas derived from three large-scale datasets comprising a total of 41,075 neurotypical participants. PCA produced a spatially broad first principal component (PC1) that was reproducible across datasets. Then PC1 derived from healthy adult participants was compared to the pattern of CT differences associated with psychiatric and neurological disorders comprising a total of 14,886 cases and 20,962 controls from seven ENIGMA disease-related working groups, normative maturation and aging comprising a total of 17,697 scans from the ABCD Study® and the IMAGEN developmental study, and 17,075 participants from the ENIGMA Lifespan working group, as well as gene expression maps from the Allen Human Brain Atlas. Results revealed substantial spatial correspondences between PC1 and widespread lower CT observed in numerous psychiatric disorders. Moreover, the PC1 pattern was also correlated with the spatial pattern of normative maturation and aging. The transcriptional analysis identified a set of genes including KCNA2, KCNS1 and KCNS2 with expression patterns closely related to the spatial pattern of PC1. The gene category enrichment analysis indicated that the transcriptional correlations of PC1 were enriched to multiple gene ontology categories and were specifically over-represented starting at late childhood, coinciding with the onset of significant cortical maturation and emergence of psychopathology during the prepubertal-to-pubertal transition. Collectively, the present study reports a reproducible latent pattern of CT that captures interregional profiles of cortical changes in both normative brain maturation and a spectrum of psychiatric disorders. The pubertal timing of the expression of PC1-related genes implicates disrupted neurodevelopment in the pathogenesis of the spectrum of psychiatric diseases emerging during adolescence.

PMID:36380235 | DOI:10.1038/s41380-022-01855-6


Zhipeng Cao
Renata B Cupertino
Jonatan Ottino-Gonzalez
Alistair Murphy
Devarshi Pancholi
Anthony Juliano
Bader Chaarani
Matthew Albaugh
Dekang Yuan
Nathan Schwab
James Stafford
Anna E Goudriaan
Kent Hutchison
Chiang-Shan R Li
Maartje Luijten
Martine Groefsema
Reza Momenan
Lianne Schmaal
Rajita Sinha
Ruth J van Holst
Dick J Veltman
Reinout W Wiers
Bernice Porjesz
Tristram Lett
Tobias Banaschewski
Arun L W Bokde
Sylvane Desrivières
Herta Flor
Antoine Grigis
Penny Gowland
Andreas Heinz
Rüdiger Brühl
Jean-Luc Martinot
Marie-Laure Paillère Martinot
Eric Artiges
Frauke Nees
Dimitri Papadopoulos Orfanos
Tomáš Paus
Luise Poustka
Sarah Hohmann
Sabina Millenet
Juliane H Fröhner
Lauren Robinson
Michael N Smolka
Henrik Walter
Jeanne Winterer
Gunter Schumann
Robert Whelan
Ravi R Bhatt
Alyssa Zhu
Patricia Conrod
Neda Jahanshad
Paul M Thompson
Scott Mackey
Hugh Garavan
IMAGEN Consortium
ENIGMA Addiction Working Group