{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T16:08:32Z","timestamp":1791130112832,"version":"4.1.0"},"reference-count":26,"publisher":"American Medical Association (AMA)","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAMA Psychiatry"],"published-print":{"date-parts":[[2025,8,1]]},"abstract":"\n Importance<\/jats:title>\n Psychiatric diagnoses are not defined by neurobiological measures hindering the development of therapies targeting mechanisms underlying mental illness. Research confined to diagnostic boundaries yields heterogeneous biological results, whereas transdiagnostic studies often investigate individual symptoms in isolation.<\/jats:p>\n <\/jats:sec>\n \n Objective<\/jats:title>\n \n To develop a framework that groups clinical symptoms compatible with\n ICD-10<\/jats:italic>\n and\n DSM-5<\/jats:italic>\n according to their covariation and shared brain mechanisms.\n <\/jats:p>\n <\/jats:sec>\n \n Design, Setting, and Participants<\/jats:title>\n This diagnostic study was conducted in 2 samples, the population-based Reinforcement-Related Behaviour in Normal Brain Function and Psychopathology (IMAGEN) cohort (longitudinal assessments at 14, 19, and 23 years; study duration from March 2010 to the present) and the cross-diagnostic Brain Network Based Stratification of Mental Illness (STRATIFY)\/Earlier Detection and Stratification of Eating Disorders and Comorbid Mental Illnesses (ESTRA) samples (study duration from October 2016 to September 2023). The samples are from 8 clinical research hospitals in Germany, the UK, France, and Ireland. For the population-based IMAGEN study, 794 of 1253 23-year-old participants had complete assessments including complete clinical assessments and neuroimaging data across all time points. For the cross-diagnostic STRATIFY\/ESTRA samples, 209 of 485 participants aged 18 to 26 years had complete clinical and neuroimaging data. The sample included healthy control individuals and patients with alcohol use disorder, major depressive disorder, anorexia nervosa, and bulimia nervosa.<\/jats:p>\n <\/jats:sec>\n \n Exposures<\/jats:title>\n Sparse generalized canonical correlation analysis was used to integrate diverse data from clinical symptoms and 7 brain imaging modalities.<\/jats:p>\n <\/jats:sec>\n \n Main Outcomes and Measures<\/jats:title>\n The prediction of symptom features was the main outcome. The model was developed in the training set from the IMAGEN Study at age 23 years (70%), then applied in the remaining holdout test sample (30%), the independent STRATIFY\/ESTRA patient sample, and longitudinally in the IMAGEN set.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n In total, 1003 participants were included (425 male and 578 female; mean [SD] age, 22.1 [1.5] years). The reassembly of existing\n ICD-10<\/jats:italic>\n and\n DSM-5<\/jats:italic>\n symptoms revealed 6 cross-diagnostic psychopathology scores. They were consistently associated with multimodal neuroimaging components: excitability and impulsivity (training set:\n r<\/jats:italic>\n , 0.26; 95% CI, 0.18-0.33; test set:\n r<\/jats:italic>\n , 0.22; 95% CI, 0.10-0.35; STRATIFY\/ESTRA set:\n r<\/jats:italic>\n , 0.19; 95% CI, 0.07-0.31), depressive mood and distress (training:\n r<\/jats:italic>\n , 0.30; 95% CI, 0.20-0.38; test:\n r<\/jats:italic>\n , 0.22; 95% CI, 0.09-0.35; STRATIFY\/ESTRA:\n r<\/jats:italic>\n , 0.19; 95% CI, 0.04-0.33), emotional and behavioral dysregulation (training:\n r<\/jats:italic>\n , 0.40; 95% CI, 0.31-0.48; test:\n r<\/jats:italic>\n , 0.17; 95% CI, 0.14-0.36; STRATIFY\/ESTRA:\n r<\/jats:italic>\n , 0.19; 95% CI, 0.06-0.30), stress pathology (training:\n r<\/jats:italic>\n , 0.32; 95% CI, 0.19-0.43; test:\n r<\/jats:italic>\n , 0.14; 95% CI, 0.05-0.23; STRATIFY\/ESTRA:\n r<\/jats:italic>\n , 0.12; 95% CI, 0.01-0.22), eating pathology (training:\n r<\/jats:italic>\n , 0.34; 95% CI, 0.25-0.42; test:\n r<\/jats:italic>\n , 0.26; 95% CI, 0.15-0.37; STRATIFY\/ESTRA:\n r<\/jats:italic>\n , 0.15; 95% CI, 0.12-0.34), and social fear and avoidance symptoms (training:\n r<\/jats:italic>\n , 0.31; 95% CI, 0.25-0.42; test:\n r<\/jats:italic>\n , 0.18; 95% CI, 0.15-0.35; STRATIFY\/ESTRA:\n r<\/jats:italic>\n , 0.12; 95% CI, 0.12-0.33).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion and Relevance<\/jats:title>\n In this study, the identification of symptom groups of mental illness robustly defined by precisely characterized brain mechanisms enabled the characterization of dimensions of psychopathology based on quantifiable neurobiological measures.<\/jats:p>\n <\/jats:sec>","DOI":"10.1001\/jamapsychiatry.2025.1246","type":"journal-article","created":{"date-parts":[[2025,6,18]],"date-time":"2025-06-18T11:00:23Z","timestamp":1750244423000},"page":"778","source":"Crossref","is-referenced-by-count":13,"title":["Framework for Brain-Derived Dimensions of Psychopathology"],"prefix":"10.1001","volume":"82","author":[{"given":"Tristram A.","family":"Lett","sequence":"first","affiliation":[{"name":"Centre for Population Neuroscience and Stratified Medicine, Department of Psychiatry and Psychotherapy, Charit\u00e9 Universit\u00e4tsmedizin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilakshi","family":"Vaidya","sequence":"additional","affiliation":[{"name":"Centre for Population Neuroscience and Stratified Medicine, Department of Psychiatry and Psychotherapy, Charit\u00e9 Universit\u00e4tsmedizin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianye","family":"Jia","sequence":"additional","affiliation":[{"name":"Institute for Science and Technology of Brain-inspired Intelligence, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elli","family":"Polemiti","sequence":"additional","affiliation":[{"name":"Centre for Population Neuroscience and Stratified Medicine, Department of Psychiatry and Psychotherapy, Charit\u00e9 Universit\u00e4tsmedizin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tobias","family":"Banaschewski","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun L. W.","family":"Bokde","sequence":"additional","affiliation":[{"name":"Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herta","family":"Flor","sequence":"additional","affiliation":[{"name":"Institute of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany"},{"name":"Department of Psychology, School of Social Sciences, University of Mannheim, Mannheim, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Grigis","sequence":"additional","affiliation":[{"name":"NeuroSpin, Commissariat \u00e0 l\u2019Energie Atomique, Universit\u00e9 Paris-Saclay, Gif-sur-Yvette, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hugh","family":"Garavan","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychology, University of Vermont, Burlington"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Penny","family":"Gowland","sequence":"additional","affiliation":[{"name":"Sir Peter Mansfield Imaging Centre School of Physics and Astronomy, University of Nottingham, University Park, Nottingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas","family":"Heinz","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, Charit\u00e9 Campus Mitte, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R\u00fcdiger","family":"Br\u00fchl","sequence":"additional","affiliation":[{"name":"Physikalisch-Technische Bundesanstalt, Braunschweig and Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Luc","family":"Martinot","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Institut national de la sant\u00e9 et de la recherche m\u00e9dicale U1299 Trajectoires d\u00e9veloppementales en psychiatrie, Universit\u00e9 Paris-Saclay, Ecole Normale sup\u00e9rieure Paris-Saclay, Centre national de la recherche scientifique Unit\u00e9 Mixte de Recherche 9010, Centre Borelli, Gif-sur-Yvette, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marie-Laure","family":"Paill\u00e8re Martinot","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Institut national de la sant\u00e9 et de la recherche m\u00e9dicale U1299 Trajectoires d\u00e9veloppementales en psychiatrie, Universit\u00e9 Paris-Saclay, Ecole Normale sup\u00e9rieure Paris-Saclay, Centre national de la recherche scientifique Unit\u00e9 Mixte de Recherche 9010, Centre Borelli, Gif-sur-Yvette, France"},{"name":"Assistance Publique-H\u00f4pitaux de Paris, Sorbonne Universit\u00e9, Department of Child and Adolescent Psychiatry, Piti\u00e9-Salp\u00eatri\u00e8re Hospital, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Artiges","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale, Universit\u00e9 Paris-Saclay Ecole Normale Sup\u00e9rieure Paris-Saclay, Centre national de la recherche scientifique Centre Borelli, Gif-sur-Yvette, France"},{"name":"Psychiatry Department, \u00c9tablissement Public de Sant\u00e9 Barth\u00e9l\u00e9my Durand, Etampes, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frauke","family":"Nees","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany"},{"name":"Institute of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany"},{"name":"Institute of Medical Psychology and Medical Sociology, University Medical Center Schleswig-Holstein, Kiel University, Kiel, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitri","family":"Papadopoulos Orfanos","sequence":"additional","affiliation":[{"name":"NeuroSpin, Commissariat \u00e0 l\u2019Energie Atomique, Universit\u00e9 Paris-Saclay, Gif-sur-Yvette, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Herve","family":"Lemaitre","sequence":"additional","affiliation":[{"name":"Institut des Maladies Neurod\u00e9g\u00e9n\u00e9ratives, Unit\u00e9 Mixte de Recherche 5293, Centre national de la recherche scientifique, Commissariat \u00e0 l\u2019Energie Atomique, Universit\u00e9 de Bordeaux, Bordeaux, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom\u00e1\u0161","family":"Paus","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Faculty of Medicine and Centre Hospitalier Universitaire Sainte-Justine, University of Montreal, Montreal, Quebec, Canada"},{"name":"Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada"},{"name":"Department of Psychiatry and Psychology, University of Toronto, Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luise","family":"Poustka","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry, Center for Psychosocial Medicine, University Hospital Heidelberg, Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Argyris","family":"Stringaris","sequence":"additional","affiliation":[{"name":"Division of Psychiatry and Department of Clinical, Educational & Health Psychology, University College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Waller","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, Charit\u00e9 Campus Mitte, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zuo","family":"Zhang","sequence":"additional","affiliation":[{"name":"Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King\u2019s College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeanne","family":"Winterer","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, Charit\u00e9 Campus Mitte, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Berlin, Germany"},{"name":"Department of Education and Psychology, Freie Universit\u00e4t Berlin, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuning","family":"Zhang","sequence":"additional","affiliation":[{"name":"Psychology Department, University of Southampton, Southampton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael N.","family":"Smolka","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, Technische Universit\u00e4t Dresden, Dresden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Whelan","sequence":"additional","affiliation":[{"name":"School of Psychology and Global Brain Health Institute, Trinity College Dublin, Dublin, Ireland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Psychological Medicine, Centre for Research in Eating and Weight Disorders, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London, London, United Kingdom"},{"name":"South London and Maudsley National Health Service Foundation Trust, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Sinclair","sequence":"additional","affiliation":[{"name":"Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Walter","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Psychotherapy, Charit\u00e9 Campus Mitte, Humboldt-Universit\u00e4t zu Berlin, and Berlin Institute of Health, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianfeng","family":"Feng","sequence":"additional","affiliation":[{"name":"Institute for Science and Technology of Brain-inspired Intelligence, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trevor W.","family":"Robbins","sequence":"additional","affiliation":[{"name":"Institute for Science and Technology of Brain-inspired Intelligence, Fudan University, Shanghai, China"},{"name":"Department of Psychology and Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvane","family":"Desrivi\u00e8res","sequence":"additional","affiliation":[{"name":"Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King\u2019s College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"Marquand","sequence":"additional","affiliation":[{"name":"Donders Institute\/Radboud University Medical Center, Nijmegen, the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunter","family":"Schumann","sequence":"additional","affiliation":[{"name":"Centre for Population Neuroscience and Stratified Medicine, Department of Psychiatry and Psychotherapy, Charit\u00e9 Universit\u00e4tsmedizin, Berlin, Germany"},{"name":"Institute for Science and Technology of Brain-inspired Intelligence, Fudan University, Shanghai, China"},{"name":"Centre for Population Neuroscience and Precision Medicine, National Center for Neurological Disorders, Huashan Hospital, Fudan University, Shanghai, China"},{"name":"Department of Psychiatry and Neuroscience, University of Cambridge, Cambridge, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"IMAGEN Consortium and the environMENTAL Consortium","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunter","family":"Schumann","sequence":"additional","affiliation":[{"name":"for the IMAGEN Consortium and the environMENTAL Consortium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Hitchen","sequence":"additional","affiliation":[{"name":"for the IMAGEN Consortium and the environMENTAL Consortium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elli","family":"Polemiti","sequence":"additional","affiliation":[{"name":"for the IMAGEN Consortium and the environMENTAL Consortium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hedi","family":"Kebir","sequence":"additional","affiliation":[{"name":"for the IMAGEN Consortium and the environMENTAL Consortium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tristram A.","family":"Lett","sequence":"additional","affiliation":[{"name":"for the IMAGEN Consortium and the environMENTAL Consortium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nilakshi","family":"Vaidya","sequence":"additional","affiliation":[{"name":"for the IMAGEN 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