Psychosis brain subtypes validated in first-episode cohorts and related to illness remission: results from the PHENOM consortium

Dominic B. Dwyer, Paola Dazzan, Ganesh B. Chand, Alessandro Pigoni, Adyasha Khuntia, Junhao Wen, Mathilde Antoniades, Gyujoon Hwang, Guray Erus, Jimit Doshi, Dhivya Srinivasan, Erdem Varol, Hugo G. Schnack, Eva Meisenzahl, Stephen Wood, Chuanjun Zhuo, Aristeidis Sotiras, Russell T. Shinohara, Haochang Shou, Yong FanPedro Rosa, Paris Alexandros Lalousis, Rachel Upthegrove, Antonia N. Kaczkurkin, Tyler M. Moore, Barnaby Nelson, Raquel E. Gur, Ruben C. Gur, Marylyn D. Ritchie, Theodore D. Satterthwaite, Robin Murray, Marta Di Forti, Simone Ciufolini, Marcus V. Zanetti, Daniel H. Wolf, C Pantelis, Benedicto Crespo-Facorro, Geraldo F. Busatto, Christos Davatzikos, Nikolaos Koutsouleris

Research output: Contribution to journalArticlepeer-review



Using machine learning, we recently decomposed the neuroanatomical heterogeneity of established schizophrenia to discover two volumetric subgroups—a ‘lower brain volume’ subgroup (SG1) and an ‘higher striatal volume’ subgroup (SG2) with otherwise normal brain structure. In this study, we investigated whether the MRI signatures of these subgroups were also already present at the time of the first-episode of psychosis (FEP) and whether they were related to clinical presentation and clinical remission over 1-, 3-, and 5-years. We included 572 FEP and 424 healthy controls (HC) from 4 sites (Sao Paulo, Santander, London, Melbourne) of the PHENOM consortium. Our prior MRI subgrouping models (671 participants; USA, Germany, and China) were applied to both FEP and HC. Participants were assigned into 1 of 4 categories: subgroup 1 (SG1), subgroup 2 (SG2), no subgroup membership (‘None’), and mixed SG1+SG2 subgroups (‘Mixed’). Voxel-wise analyses characterized SG1 and SG2 subgroups. Supervised machine learning analyses characterized baseline and remission signatures related to SG1 and SG2 membership. The two dominant patterns of ‘lower brain volume’ in SG1 and ‘higher striatal volume’ (with otherwise normal neuromorphology) in SG2 were identified already at the first episode of psychosis. SG1 had a significantly higher proportion of FEP (32%) vs. HC (19%) than SG2 (FEP, 21%; HC, 23%). Clinical multivariate signatures separated the SG1 and SG2 subgroups (balanced accuracy=64%; p
Original languageEnglish
JournalMolecular Psychiatry
Publication statusAccepted/In press - 14 Mar 2023


Dive into the research topics of 'Psychosis brain subtypes validated in first-episode cohorts and related to illness remission: results from the PHENOM consortium'. Together they form a unique fingerprint.

Cite this