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

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


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

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


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.


Cao, Z., Cupertino, R. B., Ottino-Gonzalez, J., Murphy, A., Pancholi, D., Juliano, A., …ENIGMA Addiction Working Group. (2022). Cortical profiles of numerous psychiatric disorders and normal development share a common pattern. Molecular Psychiatry,

Journal Article Type Article
Acceptance Date Oct 24, 2022
Online Publication Date Nov 15, 2022
Publication Date Nov 15, 2022
Deposit Date Nov 19, 2022
Journal Molecular Psychiatry
Print ISSN 1359-4184
Electronic ISSN 1476-5578
Publisher Springer Science and Business Media LLC
Peer Reviewed Peer Reviewed
Keywords Cellular and Molecular Neuroscience; Psychiatry and Mental health; Molecular Biology
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