ArticlemedRxiv : the preprint server for health sciences2025
Cerebral cortical alterations in adolescent early-onset psychosis: a surface-based morphometry mega-analysis.
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44 authors.
Stener NerlandDivision for Mental Health and Substance Abuse, Diakonhjemmet Hospital, Oslo, Norway.ORCID 0000-0001-8771-8856
Claudia BarthDivision for Mental Health and Substance Abuse, Diakonhjemmet Hospital, Oslo, Norway.ORCID 0000-0001-6544-0945
Kjetil Nordbø JørgensenDivision of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.ORCID 0000-0002-5751-4809
Laura A WortingerDivision for Mental Health and Substance Abuse, Diakonhjemmet Hospital, Oslo, Norway.ORCID 0000-0003-2721-3172
Josefina Castro-FornielesDepartment of Child and Adolescent Psychiatry and Psychology, Hospital Clínic of Barcelona, IDIBAPS, CIBERSAM. Department of Medicine, Insitute of Neuroscience, University of Barcelona, Barcelona, Spain.ORCID 0000-0003-0632-2687
Covadonga M Díaz-CanejaDepartment of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, IiSGM, CIBERSAM, ISCIII, Madrid, Spain.ORCID 0000-0001-8538-3175
Joost JanssenDepartment of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, IiSGM, CIBERSAM, ISCIII, Madrid, Spain.ORCID 0000-0001-7613-2067
Celso ArangoDepartment of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, IiSGM, CIBERSAM, ISCIII, Madrid, Spain.ORCID 0000-0003-3382-4754
Gisela SugranyesDepartment of Child and Adolescent Psychiatry and Psychology, Hospital Clínic of Barcelona, IDIBAPS, CIBERSAM. Barcelona, Spain.ORCID 0000-0002-2545-7862
Inmaculada BaezaDepartment of Child and Adolescent Psychiatry and Psychology, Hospital Clínic of Barcelona, IDIBAPS, CIBERSAM. Department of Medicine, Insitute of Neuroscience, University of Barcelona, Barcelona, Spain.
Fabrizio PirasLaboratory of Neuropsychiatry, Department of Clinical Neuroscience and Neurorehabilitation, Santa Lucia Foundation IRCCS, Rome, Italy.ORCID 0000-0003-3566-5494
Nerisa BanajLaboratory of Neuropsychiatry, Department of Clinical Neuroscience and Neurorehabilitation, Santa Lucia Foundation IRCCS, Rome, Italy.ORCID 0000-0002-6317-8549
Federica PirasLaboratory of Neuropsychiatry, Department of Clinical Neuroscience and Neurorehabilitation, Santa Lucia Foundation IRCCS, Rome, Italy.ORCID 0000-0002-9546-7038
Simone EliaLaboratory of Neuropsychiatry, Department of Clinical Neuroscience and Neurorehabilitation, Santa Lucia Foundation IRCCS, Rome, Italy.
Daniela VecchioLaboratory of Neuropsychiatry, Department of Clinical Neuroscience and Neurorehabilitation, Santa Lucia Foundation IRCCS, Rome, Italy.ORCID 0000-0001-8428-7376
Mathias LundbergDepartment of Clinical Science and Education Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0002-3215-1001
Hannes BohmanDepartment of Clinical Science and Education Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.ORCID 0000-0001-9726-6478
Bjørn Rishovd RundDepartment of Psychology, University of Oslo, Oslo, Norway.ORCID 0000-0002-0939-0012
Elena de la SernaDepartment of Child and Adolescent Psychiatry and Psychology, Hospital Clínic of Barcelona, IDIBAPS, CIBERSAM. Barcelona, Spain.ORCID 0000-0002-7869-9881
Adriana ForteaInstitut d'Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain.
Christian K TamnesDivision for Mental Health and Substance Abuse, Diakonhjemmet Hospital, Oslo, Norway.ORCID 0000-0002-9191-6764
Lars T WestlyeDepartment of Psychology, University of Oslo, Oslo, Norway.ORCID 0000-0001-8644-956X
Runar E SmelrorDivision for Mental Health and Substance Abuse, Diakonhjemmet Hospital, Oslo, Norway.ORCID 0000-0001-8611-6132
Dimitrios AndreouDivision for Mental Health and Substance Abuse, Diakonhjemmet Hospital, Oslo, Norway.ORCID 0000-0003-4735-3383
Erik G JönssonDivision of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Matthew J KemptonDepartment of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.ORCID 0000-0003-3541-9947
Shuqing SiDepartment of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.ORCID 0009-0006-6095-254X
Marinos Kyriakopoulos1st Department of Psychiatry, Eginition Hospital, National and Kapodistrian University of Athens, Athens, Greece.ORCID 0000-0002-4594-2646
Carrie E BeardenDepartment of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, UCLA, Los Angeles, California, USA.ORCID 0000-0002-8516-923X
Kristen LauletteDepartment of Psychology, UCLA, Los Angeles, California, USA.
Saül Pascual-DiazMagnetic Resonance Imaging Core Facility, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, Barcelona, Spain.ORCID 0000-0001-5871-5867
Anne-Kathrin J FettDepartment of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom.ORCID 0000-0003-0282-273X
Katherine H KarlsgodtDepartment of Psychology, UCLA Los Angeles, California, USA.ORCID 0000-0003-3332-4231
Lydia KrabbendamDepartment of Clinical, Neuro, and Developmental Psychology, Institute for Brain and Behavior Amsterdam, Vrije Universiteit Amsterdam, the Netherlands.ORCID 0000-0003-4074-5149
Peter KochunovDepartment of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center Houston, Houston, TX, USA.ORCID 0000-0003-3656-4281
Sophia I ThomopoulosImaging Genetics Center, Mark & Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.
Neda JahanshadImaging Genetics Center, Mark & Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.ORCID 0000-0003-4401-8950
Anthony JamesDepartment of Psychiatry, University of Oxford, Oxford, UK.ORCID 0000-0002-2742-8328
Sophia FrangouDepartment of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA.ORCID 0000-0002-3210-6470
Anne M MyhreDivision of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.ORCID 0000-0001-7702-3962
Nils Eiel SteenDivision for Mental Health and Substance Abuse, Diakonhjemmet Hospital, Oslo, Norway.ORCID 0000-0001-6442-1179
Ole A AndreassenDivision for Mental Health and Substance Abuse, Diakonhjemmet Hospital, Oslo, Norway.ORCID 0000-0002-4461-3568
Paul M ThompsonImaging Genetics Center, Mark & Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA, USA.
Ingrid AgartzDivision for Mental Health and Substance Abuse, Diakonhjemmet Hospital, Oslo, Norway.ORCID 0000-0002-9839-5391
Funding
STRESS AND EMOTIONAL REACTIVITYP50MH066286 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI NUECHTERLEIN, KEITH H · 2003 to 2014
$18.6M1/9 Predictors and Mechanisms of Conversion to PsychosisU01MH081902 · NIMH · YALE UNIVERSITY · PI CANNON, TYRONE D · 2008 to 2018
$12.4MTraining U54EB020403 · NIBIB · UNIVERSITY OF SOUTHERN CALIFORNIA · PI THOMPSON, PAUL M · 2014 to 2018
$10.1MSOLAR-Eclipse Computational Tools for Imaging GeneticsR01EB015611 · NIBIB · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI KOCHUNOV, PETER V. · 2012 to 2024
$5.0MENIGMA Bipolar Initiative: A Global Study of Imaging Genomics & Clinical OutcomesR01MH129742 · NIMH · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Christopher Ching, PAUL M THOMPSON · 2022 to 2026
$3.0MGlobal studies into the Genetic Architecture of the Brain's White Matter Network through Harmonized and Coordinated Analyses in the ENIGMA-ConsortiumR01MH134004 · NIMH · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Neda Jahanshad · 2023 to 2026
$2.6MENIGMA-SD: Understanding Sex Differences in Global Mental Health through ENIGMAR01MH116147 · NIMH · UNIVERSITY OF SOUTHERN CALIFORNIA · PI THOMPSON, PAUL M · 2018 to 2021
$2.5MA global alliance to unlock brain mechanisms influencing suicidal behaviors through the ENIGMA ConsortiumR01MH117601 · NIMH · UNIVERSITY OF SOUTHERN CALIFORNIA · PI JAHANSHAD, NEDA, SCHMAAL, LIANNE · 2018 to 2021
$1.5MRedefine Trans-Neuropsychiatric Disorder Brain Patterns through Big-Data and Machine LearningRF1MH123163 · NIMH · UNIVERSITY OF MARYLAND BALTIMORE · PI KOCHUNOV, PETER V., THOMPSON, PAUL M · 2021 to 2021
$1.2MLifespan Vascular Biology on White MatterR01NS114628 · NINDS · UNIVERSITY OF MARYLAND BALTIMORE · PI HONG, L ELLIOT ELLIOT, KOCHUNOV, PETER V. · 2024 to 2024
$770kHybrid GPU/CPU Computing Resource to Support Connectomic and GenomicsS10OD023696 · OD · UNIVERSITY OF MARYLAND BALTIMORE · PI KOCHUNOV, PETER V. · 2018 to 2018
$593kNIBIB NIH HHS R01 EB015611NIBIB NIH HHS U54 EB020403NIH HHS S10 OD023696NIMH NIH HHS P50 MH066286NIMH NIH HHS R01 MH116147NIMH NIH HHS R01 MH117601NIMH NIH HHS R01 MH129742NIMH NIH HHS R01 MH134004NIMH NIH HHS RF1 MH123163NIMH NIH HHS U01 MH081902NINDS NIH HHS R01 NS114628
Abstract
Cortical brain morphology in early-onset psychosis (EOP; age of onset < 19 years) is poorly understood, partly due to recruitment constraints linked to its low incidence. We pooled T1-weighted magnetic resonance imaging (MRI) data from 387 adolescents with EOP (mean age=16.1±1.5; 49.6% female) and 338 healthy controls (CTR; mean age=15.8±1.9, 54.4% female) from nine research sites worldwide. Using harmonized processing protocols with FreeSurfer, we extracted cortical brain metrics from 34 bilateral regions. Univariate regression analysis revealed widespread lower bilateral cortical thickness (left/right hemisphere:
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