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

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 investigate...

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Autores principales: Dwyer, Dominic B., Chand, Ganesh B., Pigoni, Alessandro, Khuntia, Adyasha, Wen, Junhao, Antoniades, Mathilde, Hwang, Gyujoon, Erus, Guray, Doshi, Jimit, Srinivasan, Dhivya, Varol, Erdem, Kahn, Rene S., Schnack, Hugo G., Meisenzahl, Eva, Wood, Stephen J., Zhuo, Chuanjun, Sotiras, Aristeidis, Shinohara, Russell T., Shou, Haochang, Fan, Yong, Schaulfelberger, Maristela, Rosa, Pedro, Lalousis, Paris A., Upthegrove, Rachel, Kaczkurkin, Antonia N., Moore, Tyler M., Nelson, Barnaby, Gur, Raquel E., Gur, Ruben C., Ritchie, Marylyn D., Satterthwaite, Theodore D., Murray, Robin M., Di Forti, Marta, Ciufolini, Simone, Zanetti, Marcus V., Wolf, Daniel H., Pantelis, Christos, Crespo-Facorro, Benedicto, Busatto, Geraldo F., Davatzikos, Christos, Koutsouleris, Nikolaos, Dazzan, Paola
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10575777/
https://www.ncbi.nlm.nih.gov/pubmed/37147389
http://dx.doi.org/10.1038/s41380-023-02069-0
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author Dwyer, Dominic B.
Chand, Ganesh B.
Pigoni, Alessandro
Khuntia, Adyasha
Wen, Junhao
Antoniades, Mathilde
Hwang, Gyujoon
Erus, Guray
Doshi, Jimit
Srinivasan, Dhivya
Varol, Erdem
Kahn, Rene S.
Schnack, Hugo G.
Meisenzahl, Eva
Wood, Stephen J.
Zhuo, Chuanjun
Sotiras, Aristeidis
Shinohara, Russell T.
Shou, Haochang
Fan, Yong
Schaulfelberger, Maristela
Rosa, Pedro
Lalousis, Paris A.
Upthegrove, Rachel
Kaczkurkin, Antonia N.
Moore, Tyler M.
Nelson, Barnaby
Gur, Raquel E.
Gur, Ruben C.
Ritchie, Marylyn D.
Satterthwaite, Theodore D.
Murray, Robin M.
Di Forti, Marta
Ciufolini, Simone
Zanetti, Marcus V.
Wolf, Daniel H.
Pantelis, Christos
Crespo-Facorro, Benedicto
Busatto, Geraldo F.
Davatzikos, Christos
Koutsouleris, Nikolaos
Dazzan, Paola
author_facet Dwyer, Dominic B.
Chand, Ganesh B.
Pigoni, Alessandro
Khuntia, Adyasha
Wen, Junhao
Antoniades, Mathilde
Hwang, Gyujoon
Erus, Guray
Doshi, Jimit
Srinivasan, Dhivya
Varol, Erdem
Kahn, Rene S.
Schnack, Hugo G.
Meisenzahl, Eva
Wood, Stephen J.
Zhuo, Chuanjun
Sotiras, Aristeidis
Shinohara, Russell T.
Shou, Haochang
Fan, Yong
Schaulfelberger, Maristela
Rosa, Pedro
Lalousis, Paris A.
Upthegrove, Rachel
Kaczkurkin, Antonia N.
Moore, Tyler M.
Nelson, Barnaby
Gur, Raquel E.
Gur, Ruben C.
Ritchie, Marylyn D.
Satterthwaite, Theodore D.
Murray, Robin M.
Di Forti, Marta
Ciufolini, Simone
Zanetti, Marcus V.
Wolf, Daniel H.
Pantelis, Christos
Crespo-Facorro, Benedicto
Busatto, Geraldo F.
Davatzikos, Christos
Koutsouleris, Nikolaos
Dazzan, Paola
author_sort Dwyer, Dominic B.
collection PubMed
description 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 < 0.0001), with SG2 showing higher education but also greater positive psychosis symptoms at first presentation, and an association with symptom remission at 1-year, 5-year, and when timepoints were combined. Neuromorphological subtypes of schizophrenia are already evident at illness onset, separated by distinct clinical presentations, and differentially associated with subsequent remission. These results suggest that the subgroups may be underlying risk phenotypes that could be targeted in future treatment trials and are critical to consider when interpreting neuroimaging literature.
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spelling pubmed-105757772023-10-15 Psychosis brain subtypes validated in first-episode cohorts and related to illness remission: results from the PHENOM consortium Dwyer, Dominic B. Chand, Ganesh B. Pigoni, Alessandro Khuntia, Adyasha Wen, Junhao Antoniades, Mathilde Hwang, Gyujoon Erus, Guray Doshi, Jimit Srinivasan, Dhivya Varol, Erdem Kahn, Rene S. Schnack, Hugo G. Meisenzahl, Eva Wood, Stephen J. Zhuo, Chuanjun Sotiras, Aristeidis Shinohara, Russell T. Shou, Haochang Fan, Yong Schaulfelberger, Maristela Rosa, Pedro Lalousis, Paris A. Upthegrove, Rachel Kaczkurkin, Antonia N. Moore, Tyler M. Nelson, Barnaby Gur, Raquel E. Gur, Ruben C. Ritchie, Marylyn D. Satterthwaite, Theodore D. Murray, Robin M. Di Forti, Marta Ciufolini, Simone Zanetti, Marcus V. Wolf, Daniel H. Pantelis, Christos Crespo-Facorro, Benedicto Busatto, Geraldo F. Davatzikos, Christos Koutsouleris, Nikolaos Dazzan, Paola Mol Psychiatry Article 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 < 0.0001), with SG2 showing higher education but also greater positive psychosis symptoms at first presentation, and an association with symptom remission at 1-year, 5-year, and when timepoints were combined. Neuromorphological subtypes of schizophrenia are already evident at illness onset, separated by distinct clinical presentations, and differentially associated with subsequent remission. These results suggest that the subgroups may be underlying risk phenotypes that could be targeted in future treatment trials and are critical to consider when interpreting neuroimaging literature. Nature Publishing Group UK 2023-05-05 2023 /pmc/articles/PMC10575777/ /pubmed/37147389 http://dx.doi.org/10.1038/s41380-023-02069-0 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Dwyer, Dominic B.
Chand, Ganesh B.
Pigoni, Alessandro
Khuntia, Adyasha
Wen, Junhao
Antoniades, Mathilde
Hwang, Gyujoon
Erus, Guray
Doshi, Jimit
Srinivasan, Dhivya
Varol, Erdem
Kahn, Rene S.
Schnack, Hugo G.
Meisenzahl, Eva
Wood, Stephen J.
Zhuo, Chuanjun
Sotiras, Aristeidis
Shinohara, Russell T.
Shou, Haochang
Fan, Yong
Schaulfelberger, Maristela
Rosa, Pedro
Lalousis, Paris A.
Upthegrove, Rachel
Kaczkurkin, Antonia N.
Moore, Tyler M.
Nelson, Barnaby
Gur, Raquel E.
Gur, Ruben C.
Ritchie, Marylyn D.
Satterthwaite, Theodore D.
Murray, Robin M.
Di Forti, Marta
Ciufolini, Simone
Zanetti, Marcus V.
Wolf, Daniel H.
Pantelis, Christos
Crespo-Facorro, Benedicto
Busatto, Geraldo F.
Davatzikos, Christos
Koutsouleris, Nikolaos
Dazzan, Paola
Psychosis brain subtypes validated in first-episode cohorts and related to illness remission: results from the PHENOM consortium
title Psychosis brain subtypes validated in first-episode cohorts and related to illness remission: results from the PHENOM consortium
title_full Psychosis brain subtypes validated in first-episode cohorts and related to illness remission: results from the PHENOM consortium
title_fullStr Psychosis brain subtypes validated in first-episode cohorts and related to illness remission: results from the PHENOM consortium
title_full_unstemmed Psychosis brain subtypes validated in first-episode cohorts and related to illness remission: results from the PHENOM consortium
title_short Psychosis brain subtypes validated in first-episode cohorts and related to illness remission: results from the PHENOM consortium
title_sort psychosis brain subtypes validated in first-episode cohorts and related to illness remission: results from the phenom consortium
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10575777/
https://www.ncbi.nlm.nih.gov/pubmed/37147389
http://dx.doi.org/10.1038/s41380-023-02069-0
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