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A shared neural basis underlying psychiatric comorbidity

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Xie, Chao 
Xiang, Shitong; orcid: 0000-0002-5513-4714 
Shen, Chun 
Peng, Xuerui; orcid: 0000-0002-8780-0910 
Kang, Jujiao 


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.


Funder: National Key R and D Program of China(2019YFA0709501,2018YFC1312900) The Shanghai Pujiang Project(18PJ1400900)

Funder: Medical Research Foundation and Medical Research Council (grants MR/R00465X/1 and MR/S020306/1); NIH Consortium grant U54 EB020403; the cross-NIH alliance that funds Big Data to Knowledge Centres of Excellence (ENIGMA, Grant Nos. 5U54EB020403-05 and 1R56AG058854-01

Funder: the Eranet Neuron (AF12-NEUR0008-01 – WM2NA; and ANR-18-NEUR00002-01 – ADORe);Paris Sud University IDEX 2012;Fédération pour la Recherche sur le Cerveau;

Funder: Assistance Publique - Hôpitaux de Paris (Assistance Publique Hôpitaux de Paris); doi:

Funder: Fondation de l'Avenir pour la Recherche Médicale Appliquée (Fondation de l'Avenir); doi:

Funder: the ANR (ANR-12-SAMA-0004); INSERM (interface grant)

Funder: DH | National Institute for Health Research (NIHR); doi:

Funder: South London and Maudsley NHS Foundation Trust; doi:

Funder: the European Union-funded FP6 Integrated Project IMAGEN (Reinforcement-related behavior in normal brain function and psychopathology) (LSHM-CT- 2007-037286);the Horizon 2020-funded ERC Advanced Grant' STRATIFY' (Brain network based stratification of reinforcement-related disorders) (695313);ERANID (Understanding the Interplay between Cultural, Biological and Subjective Factors in Drug Use Pathways) (PR-ST-0416-10004);Human Brain Project (HBP SGA 2, 785907, and HBP SGA 3, 945539);the Medical Research Council Grant' c-VEDA' (Consortium on Vulnerability to Externalising Disorders and Addictions) (MR/N000390/1) ;Forschungsnetz AERIAL 01EE1406A, 01EE1406B)

Funder: Guangdong Key Research and Development Project(No. 2018B030335001);the 111 Project (B18015);the key project of Shanghai Science and Technology (16JC1420402);


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Nature Medicine

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Nature Publishing Group US
Fondation de France (00081242)
Fondation pour la Recherche Médicale (Foundation for Medical Research in France) (DPA20140629802)
Mission Interministérielle de Lutte Contre les Drogues et les Conduites Addictives (MILDECA) (MILDECA)
Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) (No. RO1 MH085772-01A1)
Science Foundation Ireland (SFI) (No. 16/ERCD/3797)
Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research) (BMBF grants 01GS08152)
Deutsche Forschungsgemeinschaft (German Research Foundation) (DFG grants SM 80/7-2, SFB 940, TRR 265, NE 1383/14-1)
National Natural Science Foundation of China (National Science Foundation of China) (82150710554)