A shared neural basis underlying psychiatric comorbidity

Xie, Chao; Xiang, Shitong; Shen, Chun; Peng, Xuerui; Kang, Jujiao; Li, Yuzhu; Cheng, Wei; He, Shiqi; Banaschewski, Tobias; Barker, Gareth J.; Bokde, Arun L.W.; Bromberg, Uli; Büchel, Christian; Desrivières, Sylvane; Flor, Herta; Grigis, Antoine; Garavan, Hugh; Gowland, Penny; Heinz, Andreas; Ittermann, Bernd; Martinot, Jean Luc; Martinot, Marie Laure Paillère; Nees, Frauke; Orfanos, Dimitri Papadopoulos; Paus, Tomáš; Poustka, Luise; Fröhner, Juliane H.; Smolka, Michael N.; Walter, Henrik; Whelan, Robert; Sahakian, Barbara J.; Robbins, Trevor W.; Schumann, Gunter; Jia, Tianye; Feng, Jianfeng; IMAGEN Consortium; STRATIFY Consortium; ZIB Consortium

Abstract

Recent studies proposed a general psychopathology factor underlying common comorbidities among psychiatric disorders. However, its neurobiological mechanisms and generalizability remain elusive. In this study, we used a large longitudinal neuroimaging cohort from adolescence to young adulthood (IMAGEN) to define a neuropsychopathological (NP) factor across externalizing and internalizing symptoms using multitask connectomes. We demonstrate that this NP factor might represent a unified, genetically determined, delayed development of the prefrontal cortex that further leads to poor executive function. We also show this NP factor to be reproducible in multiple developmental periods, from preadolescence to early adulthood, and generalizable to the resting-state connectome and clinical samples (the ADHD-200 Sample and the STRATIFY & ESTRA Project). In conclusion, we identify a reproducible and general neural basis underlying symptoms of multiple mental health disorders, bridging multidimensional evidence from behavioral, neuroimaging and genetic substrates. These findings may help to develop new therapeutic interventions for psychiatric comorbidities.

Citation

Xie, C., Xiang, S., Shen, C., Peng, X., Kang, J., Li, Y., Cheng, W., He, S., Banaschewski, T., Barker, G. J., Bokde, A. L., Bromberg, U., Büchel, C., Desrivières, S., Flor, H., Grigis, A., Garavan, H., Gowland, P., Heinz, A., Ittermann, B., …ZIB Consortium. (2023). A shared neural basis underlying psychiatric comorbidity. Nature Medicine, 29(5), 1232-1242. https://doi.org/10.1038/s41591-023-02317-4

• Journal Article Type: Article
• Acceptance Date: Mar 20, 2023
• Online Publication Date: Apr 24, 2023
• Publication Date: 2023
• Deposit Date: Apr 12, 2023
• Publicly Available Date: Oct 25, 2023
• Journal: Nature Medicine
• Print ISSN: 1078-8956
• Electronic ISSN: 1546-170X
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 29
• Issue: 5
• Pages: 1232-1242
• DOI: https://doi.org/10.1038/s41591-023-02317-4
• Public URL: https://nottingham-repository.worktribe.com/output/19458118
• Publisher URL: https://www.nature.com/articles/s41591-023-02317-4
• Additional Information: Received: 16 March 2022; Accepted: 20 March 2023; First Online: 24 April 2023; : T.B. served in an advisory or consultancy role for Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH and Shire. He received conference support or speaker’s fee from Lilly, Medice, Novartis and Shire. He has been involved in clinical trials conducted by Shire and Viforpharma. He received royalties from Hogrefe, Kohlhammer, CIP Medien and Oxford University Press. The present work is unrelated to the above grants and relationships. G.J.B. received honoraria from General Electric Healthcare for teaching scanner programming courses. All other authors declare no competing interests.