OSCR

Cerebral cortical alterations in adolescent early-onset psychosis: a surface-based morphometry mega-analysis.

Overview

Authors: Stener Nerland1,2, Claudia Barth1,3,4, Kjetil Nordbø Jørgensen2,5, Laura A Wortinger1,2,6, Josefina Castro-Fornieles7, Covadonga M Díaz-Caneja8,9, Joost Janssen8, Celso Arango10, Gisela Sugranyes11, Inmaculada Baeza7, Fabrizio Piras12, Nerisa Banaj12, Federica Piras12, Simone Elia12, Daniela Vecchio12, Mathias Lundberg13,14, Hannes Bohman13,14, Bjørn Rishovd Rund15, Elena de la Serna11, Adriana Fortea16,17,18
and 24 other authorsChristian K Tamnes1,19, Lars T Westlye15,20,21, Runar E Smelror1, Dimitrios Andreou1,2,22, Erik G Jönsson2,20, Matthew J Kempton23, Shuqing Si23, Marinos Kyriakopoulos24,25,26, Carrie E Bearden27,28, Kristen Laulette28, Saül Pascual-Diaz29, Anne-Kathrin J Fett30,31, Katherine H Karlsgodt28,32, Lydia Krabbendam33, Peter Kochunov34, Sophia I Thomopoulos35, Neda Jahanshad35, Anthony James36,37, Sophia Frangou38, Anne M Myhre2,39, Nils Eiel Steen1,2,40, Ole A Andreassen2,21, Paul M Thompson35, Ingrid Agartz1,2,22
ORCID iDs: Stener Nerland, Claudia Barth, Kjetil Nordbø Jørgensen, Laura A Wortinger, Josefina Castro-Fornieles, Covadonga M Díaz-Caneja, Joost Janssen, Celso Arango, Gisela Sugranyes, Fabrizio Piras, Nerisa Banaj, Federica Piras, Simone Elia, Daniela Vecchio, Elena de la Serna, Adriana Fortea, Christian K Tamnes, Lars T Westlye, Matthew J Kempton, Shuqing Si, Marinos Kyriakopoulos, Carrie E Bearden, Saül Pascual-Diaz, Anne-Kathrin J Fett, Sophia I Thomopoulos, Anthony James, Sophia Frangou, Nils Eiel Steen, Ole A Andreassen, Paul M Thompson
40 affiliations
  1. Division of Mental Health and Substance Abuse, Diakonhjemmet Hospital, Oslo, Norway
  2. Division of Mental Health and Addiction, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
  3. Department of Psychiatry and Neurosciences (CCM), Charité – Universitätsmedizin Berlin, Berlin, Germany
  4. Research Unit Gender in Medicine, Charité – Universitätsmedizin Berlin, Berlin, Germany
  5. Division of Mental Health and Addiction, Vestre Viken Hospital Trust, Drammen, Norway
  6. Department of Psychology, Oslo New University College, Oslo, Norway
  7. Department of Child and Adolescent Psychiatry and Psychology, Hospital Clínic of Barcelona, IDIBAPS, CIBERSAM. Department of Medicine, Institute of Neuroscience, University of Barcelona, Barcelona, Spain
  8. Department of Child and Adolescent Psychiatry, Institute of Psychiatry and Mental Health, Hospital General Universitario Gregorio Marañón, IiSGM, CIBERSAM, ISCIII, Madrid, Spain
  9. School of Medicine, Universidad Complutense, Madrid, Spain
  10. Hospital Universitario La Paz, IdiPAZ, School of Medicine, Universidad Autónoma de Madrid, CIBERSAM, Madrid, Spain
  11. Department of Child and Adolescent Psychiatry and Psychology, Hospital Clínic of Barcelona, IDIBAPS, CIBERSAM, Barcelona, Spain
  12. Laboratory of Neuropsychiatry, Department of Clinical Neuroscience and Neurorehabilitation, Santa Lucia Foundation IRCCS, Rome, Italy
  13. Department of Clinical Science and Education Södersjukhuset, Karolinska Institutet, Stockholm, Sweden
  14. Department of Neuroscience, Child and Adolescent Psychiatry, Uppsala University, Uppsala, Sweden
  15. Department of Psychology, University of Oslo, Oslo, Norway
  16. Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), Barcelona, Spain
  17. Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain
  18. Adult Psychiatry and Psychology Department, Institute of Neurosciences, Hospital Clínic de Barcelona, Barcelona, Spain
  19. PROMENTA Research Centre, Department of Psychology, University of Oslo, Oslo, Norway
  20. KG Jebsen Centre for Neurodevelopmental Disorders, University of Oslo, Oslo, Norway
  21. Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
  22. Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet & Stockholm Health Care Services, Stockholm Region, Stockholm, Sweden
  23. Department of Psychosis Studies, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, United Kingdom
  24. 1st Department of Psychiatry, Eginition Hospital, National and Kapodistrian University of Athens, Athens, Greece
  25. Department of Child and Adolescent Psychiatry, Institute of Psychiatry Psychology and Neuroscience, King’s College London, London, UK
  26. South London and Maudsley NHS Foundation Trust, London, UK
  27. Department of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior, UCLA, Los Angeles, California USA
  28. Department of Psychology, UCLA, Los Angeles, California USA
  29. Magnetic Resonance Imaging Core Facility, August Pi i Sunyer Biomedical Research Institute (IDIBAPS), University of Barcelona, Barcelona, Spain
  30. Department of Psychological Medicine, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, UK
  31. Department of Psychology and Neuroscience, School of Health and Medical Sciences, City St George’s University of London, London, UK
  32. Department of Psychiatry and Biobehavioral Sciences, UCLA, Los Angeles, California USA
  33. Department of Clinical, Neuro, and Developmental Psychology, Institute for Brain and Behavior Amsterdam, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands
  34. Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center Houston, Houston, TX USA
  35. Imaging Genetics Center, Mark & Mary Stevens Neuroimaging & Informatics Institute, Keck School of Medicine, University of Southern California, Marina del Rey, CA USA
  36. Department of Psychiatry, University of Oxford, Oxford, UK
  37. Highfield Unit, Warneford Hospital, Oxford, UK
  38. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA
  39. Section of Child and Adolescent Mental Health Research, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
  40. Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
Institutions: University of Oslo (Norway); Diakonhjemmet Hospital (Norway); Charité - Universitätsmedizin Berlin (Germany); Vestre Viken Hospital Trust (Norway); Centro de Investigación Biomédica en Red de Salud Mental (Spain); Hospital Clínic de Barcelona (Spain); Consorci Institut D'Investigacions Biomediques August Pi I Sunyer (Spain); Universitat de Barcelona (Spain); Universidad Complutense de Madrid (Spain); Instituto de Salud Carlos III (Spain); Hospital General Universitario Gregorio Marañón (Spain); Hospital Universitario La Paz (Spain); Universidad Autónoma de Madrid (Spain); Fondazione Santa Lucia (Italy); Istituti di Ricovero e Cura a Carattere Scientifico (Italy); Uppsala University (Sweden); Karolinska Institutet (Sweden); Stockholm South General Hospital (Sweden); Oslo University Hospital (Norway); Stockholm Health Care Services (Sweden); King's College London (United Kingdom); South London and Maudsley NHS Foundation Trust (United Kingdom); National and Kapodistrian University of Athens (Greece); Eginition Hospital (Greece); University of California, Los Angeles (United States); St George's, University of London (United Kingdom); City St George's, University of London (United Kingdom); Vrije Universiteit Amsterdam (Netherlands); The University of Texas Health Science Center at Houston (United States); University of Southern California (United States); Warneford Hospital (United Kingdom); University of Oxford (United Kingdom); Icahn School of Medicine at Mount Sinai (United States)
Journal: Molecular psychiatry, volume 31, issue 10, pages 5574-5585
Dates: received 26 May 2025; accepted 30 April 2026; published online 19 May 2026; in print 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1038/s41380-026-03641-0 · PMID 42156536 · PMCID PMC13569444 · OpenAlex W4410806562
Open access: hybrid, a free copy (OpenAlex)
Preprint: doi:10.1101/2025.05.24.25328176
Status: code on request
Categories: structural MRI / diffusion (modality), human (organism), schizophrenia / psychosis (population), developmental (subfield)
Methods: Statistics, Connectivity, Preprocessing
Keywords: Diseases, Neuroscience
MeSH: Cerebral Cortex*, Psychotic Disorders*, Adolescent, Age of Onset, Brain, Female, Humans, Magnetic Resonance Imaging, Male, Schizophrenia (* major topic)
Topic: Functional Brain Connectivity Studies (Cognitive Neuroscience, Neuroscience), according to OpenAlex
Funding: NIBIB NIH HHS (R01 EB015611, U54 EB020403); NIH HHS (S10 OD023696); NIMH NIH HHS (P50 MH066286, R01 MH117601, R01 MH134004, U01 MH081902, R01 MH129742, R01 MH116147); Norges Forskningsråd (Research Council of Norway) (223273, 274359, 2137000, 250358, 288083, 323951)
Citations: cited by 1 paper (Europe PMC); 102 references in the paper

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, we extracted cortical brain metrics from 34 bilateral regions. Univariate regression analyses revealed widespread lower bilateral cortical thickness (left/right hemisphere: d = −0.36/−0.31), surface area (left/right: d = −0.42/−0.41), cortical volume (left/right: d = −0.58/−0.56), and Local Gyrification Index (LGI; left/right: d = −0.39/−0.52) in EOP relative to CTR. Diagnostic subgroup analyses showed broader and more pronounced case-control differences in early-onset schizophrenia for area, volume, and LGI. We found no associations with antipsychotic medication use, illness duration, age of onset, or positive symptoms. Negative symptoms were related to smaller left lingual volume (partial r = −0.21; pFDR = 0.014) and antidepressant users had smaller area (d = −0.43; pFDR = 0.034) and volume (d = −0.50; pFDR = 0.003) of the right rostral anterior cingulate compared to non-users. Cortical thickness alterations in EOP showed a similar pattern to those observed in prior studies on adults with schizophrenia (SCZ; r = 0.62) and bipolar disorders (BD; r = 0.61). However, surface area alterations were overall 1.5 times greater for EOP than adult SCZ and 4.6 times greater than adult BD. In the largest study of its kind, we observed a widespread pattern of cortical alterations in adolescents with psychotic disorders, highlighting the potential impact of aberrant neurodevelopment on cortical morphology in this clinical group.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.

The paper's code and data availability statement is in the Data section.

Tracing map

A tracing map links a paper to the code its authors published: this paper has none (its code is available on request), so it has no map.

Data

No dataset and no data link were found in the paper.

Data availability

Study results, analysis scripts, and supporting data are available from the corresponding authors upon reasonable request, subject to approval by the principal investigators and completion of applicable ethical approvals and data transfer agreements.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 2, 28 September 2026

  • Publisher: — → Springer Nature

Version 1, 28 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 44 authors, 2 keywords, 10 MeSH terms, 4 funders, 93 references.

Cite

This paper

Nerland, S., Barth, C., Jørgensen, K. N., Wortinger, L. A., Castro-Fornieles, J., Díaz-Caneja, C. M., Janssen, J., Arango, C., Sugranyes, G., Baeza, I., Piras, F., Banaj, N., Piras, F., Elia, S., Vecchio, D., Lundberg, M., Bohman, H., Rund, B. R., de la Serna, E., . . . Agartz, I. (2026). Cerebral cortical alterations in adolescent early-onset psychosis: a surface-based morphometry mega-analysis. Molecular psychiatry, 31(10), 5574-5585. https://doi.org/10.1038/s41380-026-03641-0

BibTeX

@article{nerland2026cerebral,
author = {Nerland, Stener and Barth, Claudia and Jørgensen, Kjetil Nordbø and Wortinger, Laura A and Castro-Fornieles, Josefina and Díaz-Caneja, Covadonga M and Janssen, Joost and Arango, Celso and Sugranyes, Gisela and Baeza, Inmaculada and Piras, Fabrizio and Banaj, Nerisa and Piras, Federica and Elia, Simone and Vecchio, Daniela and Lundberg, Mathias and Bohman, Hannes and Rund, Bjørn Rishovd and de la Serna, Elena and Fortea, Adriana and Tamnes, Christian K and Westlye, Lars T and Smelror, Runar E and Andreou, Dimitrios and Jönsson, Erik G and Kempton, Matthew J and Si, Shuqing and Kyriakopoulos, Marinos and Bearden, Carrie E and Laulette, Kristen and Pascual-Diaz, Saül and Fett, Anne-Kathrin J and Karlsgodt, Katherine H and Krabbendam, Lydia and Kochunov, Peter and Thomopoulos, Sophia I and Jahanshad, Neda and James, Anthony and Frangou, Sophia and Myhre, Anne M and Steen, Nils Eiel and Andreassen, Ole A and Thompson, Paul M and Agartz, Ingrid},
title = {{Cerebral cortical alterations in adolescent early-onset psychosis: a surface-based morphometry mega-analysis}},
journal = {Molecular psychiatry},
year = {2026},
month = may,
volume = {31},
number = {10},
pages = {5574--5585},
publisher = {Springer Nature},
issn = {1359-4184},
doi = {10.1038/s41380-026-03641-0},
url = {https://doi.org/10.1038/s41380-026-03641-0},
pmid = {42156536},
pmcid = {PMC13569444}
}

RIS

TY - JOUR
AU - Nerland, Stener
AU - Barth, Claudia
AU - Jørgensen, Kjetil Nordbø
AU - Wortinger, Laura A
AU - Castro-Fornieles, Josefina
AU - Díaz-Caneja, Covadonga M
AU - Janssen, Joost
AU - Arango, Celso
AU - Sugranyes, Gisela
AU - Baeza, Inmaculada
AU - Piras, Fabrizio
AU - Banaj, Nerisa
AU - Piras, Federica
AU - Elia, Simone
AU - Vecchio, Daniela
AU - Lundberg, Mathias
AU - Bohman, Hannes
AU - Rund, Bjørn Rishovd
AU - de la Serna, Elena
AU - Fortea, Adriana
AU - Tamnes, Christian K
AU - Westlye, Lars T
AU - Smelror, Runar E
AU - Andreou, Dimitrios
AU - Jönsson, Erik G
AU - Kempton, Matthew J
AU - Si, Shuqing
AU - Kyriakopoulos, Marinos
AU - Bearden, Carrie E
AU - Laulette, Kristen
AU - Pascual-Diaz, Saül
AU - Fett, Anne-Kathrin J
AU - Karlsgodt, Katherine H
AU - Krabbendam, Lydia
AU - Kochunov, Peter
AU - Thomopoulos, Sophia I
AU - Jahanshad, Neda
AU - James, Anthony
AU - Frangou, Sophia
AU - Myhre, Anne M
AU - Steen, Nils Eiel
AU - Andreassen, Ole A
AU - Thompson, Paul M
AU - Agartz, Ingrid
TI - Cerebral cortical alterations in adolescent early-onset psychosis: a surface-based morphometry mega-analysis
T2 - Molecular psychiatry
J2 - Mol Psychiatry
PY - 2026
DA - 2026/05/19
VL - 31
IS - 10
SP - 5574
EP - 5585
SN - 1359-4184
PB - Springer Nature
DO - 10.1038/s41380-026-03641-0
UR - https://doi.org/10.1038/s41380-026-03641-0
LA - en
ER -

CSL-JSON

{
"id": "10.1038/s41380-026-03641-0",
"type": "article-journal",
"title": "Cerebral cortical alterations in adolescent early-onset psychosis: a surface-based morphometry mega-analysis",
"container-title": "Molecular psychiatry",
"author": [
{
"family": "Nerland",
"given": "Stener"
},
{
"family": "Barth",
"given": "Claudia"
},
{
"family": "Jørgensen",
"given": "Kjetil Nordbø"
},
{
"family": "Wortinger",
"given": "Laura A"
},
{
"family": "Castro-Fornieles",
"given": "Josefina"
},
{
"family": "Díaz-Caneja",
"given": "Covadonga M"
},
{
"family": "Janssen",
"given": "Joost"
},
{
"family": "Arango",
"given": "Celso"
},
{
"family": "Sugranyes",
"given": "Gisela"
},
{
"family": "Baeza",
"given": "Inmaculada"
},
{
"family": "Piras",
"given": "Fabrizio"
},
{
"family": "Banaj",
"given": "Nerisa"
},
{
"family": "Piras",
"given": "Federica"
},
{
"family": "Elia",
"given": "Simone"
},
{
"family": "Vecchio",
"given": "Daniela"
},
{
"family": "Lundberg",
"given": "Mathias"
},
{
"family": "Bohman",
"given": "Hannes"
},
{
"family": "Rund",
"given": "Bjørn Rishovd"
},
{
"family": "de la Serna",
"given": "Elena"
},
{
"family": "Fortea",
"given": "Adriana"
},
{
"family": "Tamnes",
"given": "Christian K"
},
{
"family": "Westlye",
"given": "Lars T"
},
{
"family": "Smelror",
"given": "Runar E"
},
{
"family": "Andreou",
"given": "Dimitrios"
},
{
"family": "Jönsson",
"given": "Erik G"
},
{
"family": "Kempton",
"given": "Matthew J"
},
{
"family": "Si",
"given": "Shuqing"
},
{
"family": "Kyriakopoulos",
"given": "Marinos"
},
{
"family": "Bearden",
"given": "Carrie E"
},
{
"family": "Laulette",
"given": "Kristen"
},
{
"family": "Pascual-Diaz",
"given": "Saül"
},
{
"family": "Fett",
"given": "Anne-Kathrin J"
},
{
"family": "Karlsgodt",
"given": "Katherine H"
},
{
"family": "Krabbendam",
"given": "Lydia"
},
{
"family": "Kochunov",
"given": "Peter"
},
{
"family": "Thomopoulos",
"given": "Sophia I"
},
{
"family": "Jahanshad",
"given": "Neda"
},
{
"family": "James",
"given": "Anthony"
},
{
"family": "Frangou",
"given": "Sophia"
},
{
"family": "Myhre",
"given": "Anne M"
},
{
"family": "Steen",
"given": "Nils Eiel"
},
{
"family": "Andreassen",
"given": "Ole A"
},
{
"family": "Thompson",
"given": "Paul M"
},
{
"family": "Agartz",
"given": "Ingrid"
}
],
"container-title-short": "Mol Psychiatry",
"volume": "31",
"issue": "10",
"page": "5574-5585",
"DOI": "10.1038/s41380-026-03641-0",
"PMID": "42156536",
"PMCID": "PMC13569444",
"ISSN": "1359-4184",
"publisher": "Springer Nature",
"URL": "https://doi.org/10.1038/s41380-026-03641-0",
"language": "en",
"issued": {
"date-parts": [
[
2026,
5,
19
]
]
}
}

Similar papers

The papers with a page that share the most with this one: the tools found in their code, their categories, datasets, cited references and authors, the rarest counting most.

[1] doi:10.64898/2026.08.13.26360304 [code]
Lifespan brain structural variation reveals shared organization across mental health conditions
Journal: medRxiv (preprint)
In common: 5 references, 6 authors
[2] doi:10.1038/s41467-026-74153-2 [code]
Regional, functional and transcriptomic decoding of multidimensional brain structure alterations in obsessive-compulsive disorder.
Journal: Nature communications
In common: 2 references, 6 authors
[3] doi:10.21203/rs.3.rs-9246968/v1 [code]
Copy number variants reveal divergent genetic and diagnostic cortical signatures across psychiatric disorders
Journal: Research Square (preprint)
In common: 3 references, 3 authors
[4] doi:10.1038/s41467-026-72875-x [code]
Lifespan normative modeling of brain microstructure.
Journal: Nature communications
In common: schizophrenia / psychosis, structural MRI / diffusion, 2 references, 3 authors
[5] doi:10.1038/s41380-026-03547-x [code]
Multiscale characterization of cortical signatures in positive and negative schizotypy: a worldwide ENIGMA study.
Journal: Molecular psychiatry
In common: schizophrenia / psychosis, structural MRI / diffusion, 7 references, author Anne-Kathrin J Fett
[6] doi:10.1038/s41398-026-04189-x [code]
Decomposing neuroanatomical heterogeneity in depression: insights from an ENIGMA major depressive disorder working group study in 5146 individuals.
Journal: Translational psychiatry
In common: structural MRI / diffusion, 4 references, 2 authors
[7] doi:10.1038/s41398-026-04078-3 [code]
Brain age prediction in generalized anxiety disorder using a convolutional neural network.
Journal: Translational psychiatry
In common: structural MRI / diffusion, 3 references, 2 authors
[8] doi:10.1038/s43856-026-01510-z [code]
Mapping genetic convergence across brain structure, mental health, and cardiometabolic disease.
Journal: Communications medicine
In common: developmental, 3 references, author Ole A. Andreassen
[9] doi:10.1038/s41593-026-02359-0 [code]
The cross-site reproducibility of MRI morphometric phenotypes in psychiatric disorders.
Journal: Nature neuroscience
In common: schizophrenia / psychosis, structural MRI / diffusion, 6 references
[10] doi:10.21203/rs.3.rs-9914920/v1 [code]
Prediction of cognitive performance by demographics, sleep, and brain morphometry: machine learning findings from ENIGMA-Sleep Working Group
Journal: Research Square (preprint)
In common: structural MRI / diffusion, 2 authors

Contribute

The authors of this paper can claim it, correct its record and validate its tracing map, and the maintainers of its code (its owner, or a public member of its organization) correct what it says of their repository; anyone signed in can ask for its removal. Every request goes to OSCR's own machine, which answers it; your account page follows them.

Sign in with ORCID to claim this paper as one of its authors, correct its record or validate its tracing map: when the paper's metadata lists your ORCID iD, you are recognized at once. Maintainers of its code: sign in with GitHub, then claim the repository on your account page.

Request its removal

To ask OSCR to remove this record, the copies of its authors' scripts or its tracing map, use the removal request page: signed in, you say who you are, what to remove and why, then review and confirm the request. Published rules decide every request (how).

Discussion, reproductions, activity

Discussion: questions and error reports about this paper and its code, from signed-in readers and its authors. It opens with sign-in.

Reproductions: reports from readers who ran the authors' code: what they reproduced, with which environment, commit and data. It opens with sign-in.

Activity: what happens around this paper: new versions of its record, its map's validation, discussions and reproductions. It opens with sign-in.