TY - JOUR
T1 - A shared neural basis underlying psychiatric comorbidity
AU - IMAGEN Consortium
AU - Xie, Chao
AU - Xiang, Shitong
AU - Shen, Chun
AU - Peng, Xuerui
AU - Kang, Jujiao
AU - Li, Yuzhu
AU - Cheng, Wei
AU - He, Shiqi
AU - Banaschewski, Tobias
AU - Barker, Gareth J
AU - Bokde, Arun L W
AU - Bromberg, Uli
AU - Büchel, Christian
AU - Desrivières, Sylvane
AU - Flor, Herta
AU - Grigis, Antoine
AU - Garavan, Hugh
AU - Gowland, Penny
AU - Heinz, Andreas
AU - Ittermann, Bernd
AU - Martinot, Jean-Luc
AU - Martinot, Marie-Laure Paillère
AU - Nees, Frauke
AU - Orfanos, Dimitri Papadopoulos
AU - Paus, Tomáš
AU - Poustka, Luise
AU - Fröhner, Juliane H
AU - Smolka, Michael N
AU - Walter, Henrik
AU - Whelan, Robert
AU - Sahakian, Barbara J
AU - Robbins, Trevor W
AU - Schumann, Gunter
AU - Jia, Tianye
AU - Feng, Jianfeng
N1 - Funding Information:
This work received support from the following sources: the National Natural Science Foundation of China (T2122005 and 81801773 to T.J., 82150710554 to G.S.), Ministry of Education (MOE) Frontiers Center for Brain Science (to C.X.), National Key R&D Program of China (2023ZY1068, 2019YFA0709501, 2021YFC2501402 and 2018YFC1312900 to T.J.; 2019YFA0709502 and 2018YFC1312904 to J.F.), the Shanghai Pujiang Project (18PJ1400900 to T.J.), Guangdong Key Research and Development Project (2018B030335001 to J.F.), the European Union-funded FP6 Integrated Project IMAGEN (reinforcement-related behavior in normal brain function and psychopathology; LSHM-CT- 2007-037286 to G.S.), the Horizon 2020-funded European Research Council Advanced Grant for STRATIFY (brain network-based stratification of reinforcement-related disorders; 695313 to G.S.), the 111 Project (B18015 to J.F.), the key project of Shanghai Science and Technology (16JC1420402 to J.F.), Shanghai Municipal Science and Technology Major Project (2018SHZDZX01 to J.F.), Zhang Jiang Lab (to J.F.), Shanghai Center for Brain Science and Brain-Inspired Technology (to J.F.), ERANID (Understanding the Interplay between Cultural, Biological and Subjective Factors in Drug Use Pathways; PR-ST-0416-10004 to G.S.), Human Brain Project (HBP SGA 2, 785907, and HBP SGA 3, 945539, to G.S.), the Medical Research Council Grant for c-VEDA (Consortium on Vulnerability to Externalising Disorders and Addictions; MR/N000390/1 to G.S.), the National Institute of Health (NIH) (a decentralized macro and micro gene-by-environment interaction analysis of substance use behavior and its brain biomarkers; R01DA049238 to G.S.), the National Institute for Health Research Biomedical Research Centre at South London and Maudsley National Health Service Foundation Trust and King’s College London, the Bundesministeriumfür Bildung und Forschung (grants 01GS08152 and 01EV0711 to G.S.), the European Union and UK Research and Innovation-funded project environMENTAL (101057429 to G.S. and 10038599 to S.D.), Forschungsnetz AERIAL (01EE1406A and 01EE1406B to G.S.), Forschungsnetz IMAC-Mind (01GL1745B to G.S.), the Deutsche Forschungsgemeinschaft (SM 80/7-2, SFB 940, TRR 265 and NE 1383/14-1 to G.S.), the Medical Research Foundation and Medical Research Council (MR/R00465X/1, MR/S020306/1 and MRF-058-0009-RG-DESR-C0759 to S.D.) and NIH-funded ENIGMA project (5U54EB020403-05 and 1R56AG058854-01 to S.D.). Further support was provided by grants from the L’Agence nationale de la recherche (ANR) (ANR-12-SAMA-0004 to M.-L.P.M., and AAPG2019 – GeBra and ANR-18-NEUR00002-01 – ADORe to J.-L.M.); the Eranet Neuron (AF12-NEUR0008-01 – WM2NA to J.-L.M.); the Fondation de France (00081242 to J.-L.M.); the Fondation pour la Recherche Médicale (DPA20140629802 to J.-L.M.); the Mission Interministérielle de Lutte-contre-les-Drogues-et-les-Conduites-Addictives (MILDECA to J.-L.M.); the Assistance Publique–Hôpitaux de Paris and Institut National de la Santé et de la Recherche Médicale (interface grant to M.-L.P.M.); Paris Sud University IDEX 2012 (to J.-L.M.); the Fondation de l’Avenir (AP-RM-17-013 to M.-L.P.M.); the Fédération pour la Recherche sur le Cerveau; and the NIH, Science Foundation Ireland (16/ERCD/3797 to R.W.), USA (Axon, Testosterone and Mental Health during Adolescence; RO1 MH085772-01A1 to T.P.), NIH consortium (5U54 EB020403-05 to S.D.), supported by a cross-NIH alliance that funds Big Data to Knowledge Centres of Excellence (ENIGMA; 5U54EB020403-05 and 1R56AG058854-01 to S.D.).
Publisher Copyright:
© 2023, The Author(s).
PY - 2023/4/24
Y1 - 2023/4/24
N2 - 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 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.
AB - 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 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.
UR - http://www.scopus.com/inward/record.url?scp=85153790250&partnerID=8YFLogxK
U2 - 10.1038/s41591-023-02317-4
DO - 10.1038/s41591-023-02317-4
M3 - Article
C2 - 37095248
SN - 1078-8956
VL - 29
SP - 1232
EP - 1242
JO - Nature Medicine
JF - Nature Medicine
IS - 5
ER -