Mapping gray and white matter volume abnormalities in early-onset psychosis: an ENIGMA multicenter voxel-based morphometry study

Shuqing Si; Anbreen Bi; Zhaoying Yu; Cheryl See; Sinead Kelly; Sonia Ambrogi; Celso Arango; Inmaculada Baeza; Nerisa Banaj; Michael Berk; Josefina Castro-Fornieles; Benedicto Crespo-Facorro; Jacob J Crouse; Covadonga M Díaz-Caneja; Anne-Kathrin Fett; Adriana Fortea; Sophia Frangou; Benjamin I Goldstein; Ian B Hickie; Joost Janssen; Kody G Kennedy; Lydia Krabbendam; Marinos Kyriakopoulos; Bradley J MacIntosh; Pedro Morgado; Stener Nerland; Saül Pascual-Diaz; Maria Picó-Pérez; Fabrizio Piras; Bjørn Rishovd Rund; Elena de la Serna; Gianfranco Spalletta; Gisela Sugranyes; Chao Suo; Diana Tordesillas-Gutiérrez; Daniela Vecchio; Joaquim Radua; Philip McGuire; Sophia I Thomopoulos; Neda Jahanshad; Paul M Thompson; Claudia Barth; Ingrid Agartz; Anthony James; Matthew J Kempton

doi:10.1038/s41380-023-02343-1

Mapping gray and white matter volume abnormalities in early-onset psychosis: an ENIGMA multicenter voxel-based morphometry study

Mol Psychiatry. 2024 Jan 10. doi: 10.1038/s41380-023-02343-1. Online ahead of print.

Authors

Shuqing Si¹, Anbreen Bi², Zhaoying Yu², Cheryl See², Sinead Kelly², Sonia Ambrogi³, Celso Arango^{4

5}, Inmaculada Baeza⁶, Nerisa Banaj³, Michael Berk⁷, Josefina Castro-Fornieles⁶, Benedicto Crespo-Facorro⁸, Jacob J Crouse⁹, Covadonga M Díaz-Caneja^{4

5}, Anne-Kathrin Fett^{2

10}, Adriana Fortea⁶, Sophia Frangou^{11

12}, Benjamin I Goldstein^{13

14

15}, Ian B Hickie⁹, Joost Janssen⁴, Kody G Kennedy^{13

14}, Lydia Krabbendam¹⁶, Marinos Kyriakopoulos^{17

18

19}, Bradley J MacIntosh^{20

21}, Pedro Morgado^{22

23

24}, Stener Nerland^{25

26}, Saül Pascual-Diaz²⁷, Maria Picó-Pérez^{22

23

28}, Fabrizio Piras³, Bjørn Rishovd Rund^{29

30}, Elena de la Serna⁶, Gianfranco Spalletta^{3

31}, Gisela Sugranyes⁶, Chao Suo³², Diana Tordesillas-Gutiérrez^{33

34}, Daniela Vecchio³, Joaquim Radua³⁵, Philip McGuire³⁶, Sophia I Thomopoulos³⁷, Neda Jahanshad³⁷, Paul M Thompson³⁷, Claudia Barth^{25

26}, Ingrid Agartz^{25

26

38}, Anthony James^#^{36

39}, Matthew J Kempton^#²

Affiliations

¹ Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom. shuqing.si@kcl.ac.uk.
² Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
³ Laboratory of Neuropsychiatry, Santa Lucia Foundation IRCCS, Rome, Italy.
⁴ Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, IiSGM, CIBERSAM, Madrid, Spain.
⁵ School of Medicine, Universidad Complutense, Madrid, Spain.
⁶ Department of Child and Adolescent Psychiatry and Psychology, 2021SGR01319, Hospital Clinic Barcelona. CIBERSAM-ISCIII. Fundació de Recerca Clínic Barcelona - August Pi i Sunyer Biomedical Research Institute (FCRB-IDIBAPS). Institute of Neuroscience, Department of Medicine, University of Barcelona, Barcelona, Spain.
⁷ Deakin University, Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Barwon Health, Geelong, Australia.
⁸ Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Department of Psychiatry, CIBERSAM, IBiS-CSIC, Sevilla, Spain.
⁹ Brain and Mind Centre, University of Sydney, Sydney, Australia.
¹⁰ Department of Psychology, City, University of London, London, UK.
¹¹ Department of Psychiatry, University of British Columbia, Vancouver, BC, Canada.
¹² Icahn School of Medicine at Mount Sinai, New York, NY, USA.
¹³ Centre for Youth Bipolar Disorder, Centre for Addiction and Mental Health, Toronto, ON, Canada.
¹⁴ Department of Pharmacology & Toxicology, University of Toronto, Toronto, ON, Canada.
¹⁵ Department of Psychiatry, University of Toronto, Toronto, Canada.
¹⁶ Department of Clinical, Neuro and Developmental Psychology, Faculty of Behavioural and Movement Sciences, Institute for Brain and Behaviour (IBBA) Amsterdam, Vrije Universiteit Amsterdam, Amsterdam, The Netherlands.
¹⁷ 1st Department of Psychiatry, National and Kapodistrian University of Athens, Athens, Greece.
¹⁸ Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.
¹⁹ South London and Maudsley NHS Foundation Trust, London, United Kingdom.
²⁰ Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada.
²¹ Hurvitz Brain Sciences Program, Sunnybrook Research Institute, Toronto, ON, Canada.
²² Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Braga, Portugal.
²³ ICVS/3B's, PT Government Associate Laboratory, Braga/Guimarães, Portugal.
²⁴ 2CA-Braga Cinical Academic Center, Hospital de Braga, 4710-243, Braga, Portugal.
²⁵ Department of Psychiatric Research, Diakonhjemmet Hospital, Oslo, Norway.
²⁶ Norwegian Centre for Mental Disorders Research (NORMENT), Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
²⁷ Laboratory of Surgical Neuroanatomy, Universitat de Barcelona, Barcelona, Spain.
²⁸ Departamento de Psicología Básica, Clínica y Psicobiología, Universitat Jaume I, Castelló de la Plana, Spain.
²⁹ Research Department, Vestre Viken Hospital Trust, 3004, Drammen, Norway.
³⁰ Department of Psychology, University of Oslo, P. O. box 1094, Blindern, 0317, Oslo, Norway.
³¹ Menninger Department of Psychiatry and Behavioral Sciences, Baylor College of Medicine, Houston, TX, USA.
³² Turner Institute for Brain and Mental Health and School of Psychological Sciences, Monash University, Melbourne, VIC, Australia.
³³ Department of Radiology, Marqués de Valdecilla University Hospital, Valdecilla Biomedical Research Institute IDIVAL, Santander (Cantabria), Spain.
³⁴ Advanced Computing and e-Science, Instituto de Física de Cantabria (UC-CSIC), Santander (Cantabria), Spain.
³⁵ Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), CIBERSAM, University of Barcelona, Barcelona, Spain.
³⁶ Department of Psychiatry, University of Oxford, Oxford, UK.
³⁷ Imaging Genetics Center, Mark & Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.
³⁸ Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institute & Stockholm Health Care Services, Stockholm Region, Stockholm, Sweden.
³⁹ Highfield Unit, Warneford Hospital, Oxford, UK.

^# Contributed equally.

PMID: 38195979
DOI: 10.1038/s41380-023-02343-1

Abstract

Introduction: Regional gray matter (GM) alterations have been reported in early-onset psychosis (EOP, onset before age 18), but previous studies have yielded conflicting results, likely due to small sample sizes and the different brain regions examined. In this study, we conducted a whole brain voxel-based morphometry (VBM) analysis in a large sample of individuals with EOP, using the newly developed ENIGMA-VBM tool.

Methods: 15 independent cohorts from the ENIGMA-EOP working group participated in the study. The overall sample comprised T1-weighted MRI data from 482 individuals with EOP and 469 healthy controls. Each site performed the VBM analysis locally using the standardized ENIGMA-VBM tool. Statistical parametric T-maps were generated from each cohort and meta-analyzed to reveal voxel-wise differences between EOP and healthy controls as well as the individual-based association between GM volume and age of onset, chlorpromazine (CPZ) equivalent dose, and other clinical variables.

Results: Compared with healthy controls, individuals with EOP showed widespread lower GM volume encompassing most of the cortex, with the most marked effect in the left median cingulate (Hedges' g = 0.55, p = 0.001 corrected), as well as small clusters of lower white matter (WM), whereas no regional GM or WM volumes were higher in EOP. Lower GM volume in the cerebellum, thalamus and left inferior parietal gyrus was associated with older age of onset. Deficits in GM in the left inferior frontal gyrus, right insula, right precentral gyrus and right superior frontal gyrus were also associated with higher CPZ equivalent doses.

Conclusion: EOP is associated with widespread reductions in cortical GM volume, while WM is affected to a smaller extent. GM volume alterations are associated with age of onset and CPZ equivalent dose but these effects are small compared to case-control differences. Mapping anatomical abnormalities in EOP may lead to a better understanding of the role of psychosis in brain development during childhood and adolescence.