Evidence map›Paper›PMID 42238402›Full record

ArticlemedRxiv : the preprint server for health sciences2026

The Hidden Architecture of Brain Structural Variability in 22q11.2 Deletion Syndrome: A Multi-site Study.

Rune Boen, Kathleen P O'Hora, Hoki Fung, Leila Kushan, Charles H Schleifer, Tyler E Dietterich, Carolyn M Amir, Samuel Klein, Jee Won Kang, Haley R Wang and 51 more

Abstract readPreprint
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

61 authors.

Rune BoenDepartment of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior and Department of Psychology, University of California Los Angeles, Los Angeles, CA, USA.
Kathleen P O'HoraDepartment of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior and Department of Psychology, University of California Los Angeles, Los Angeles, CA, USA.
Hoki FungDepartment of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior and Department of Psychology, University of California Los Angeles, Los Angeles, CA, USA.
Leila KushanDepartment of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior and Department of Psychology, University of California Los Angeles, Los Angeles, CA, USA.
Charles H SchleiferDepartment of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior and Department of Psychology, University of California Los Angeles, Los Angeles, CA, USA.
Tyler E DietterichDepartment of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior and Department of Psychology, University of California Los Angeles, Los Angeles, CA, USA.
Carolyn M AmirDepartment of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior and Department of Psychology, University of California Los Angeles, Los Angeles, CA, USA.
Samuel KleinDepartment of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior and Department of Psychology, University of California Los Angeles, Los Angeles, CA, USA.
Jee Won KangDepartment of Psychology, University of California Los Angeles, Los Angeles, CA, USA.
Haley R WangDepartment of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior and Department of Psychology, University of California Los Angeles, Los Angeles, CA, USA.
Dylan E HughesDepartment of Psychology, University of California Los Angeles, Los Angeles, CA, USA.
Julio E Villalon-ReinaImaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, University of Southern California, Los Angeles, CA, USA.
Melody J Y KangImaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, University of Southern California, Los Angeles, CA, USA.
Yanghee ImImaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, University of Southern California, Los Angeles, CA, USA.
Kuldeep KumarCentre de recherche CHU Sainte-Justine and University of Montreal, Canada.
Dag AlnæsDepartment of Psychology, University of Oslo, Oslo, Norway.
Kathleen AngkustsiriDepartment of Pediatrics, University of California, Davis, Sacramento, CA, USA.
Kevin M AntshelDepartment of Psychology, Syracuse University, Syracuse, NY, USA.
Geor BakkerMental Health and Neuroscience Research Institute (MHeNs), Maastricht University, Maastricht, The Netherlands.
Anne S BassettClinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Nancy J ButcherDepartment of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
Linda E CampbellSchool of Psychological Sciences, College of Science, Engineering and Environment, University of Newcastle, Australia.
Samuel J R A ChawnerCentre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
Eva W C ChowCentre for Addiction and Mental Health, University of Toronto, Toronto, ON, Canada.
Michael C CraigDepartment of Forensic and Neurodevelopmental Sciences and the Sackler Institute for Translational Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, UK.
Nicolas A CrossleyDepartment of Psychiatry, Pontificia Universidad Católica de Chile, Santiago, Chile.
Eileen DalyDepartment of Forensic and Neurodevelopmental Sciences and the Sackler Institute for Translational Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, UK.
Fabio Di FabioDepartment of Human Neurosciences, Sapienza University, Rome, Italy.
Joanne L DohertyCentre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
Beverly S EmanuelDepartment of Pediatrics, University of Pennsylvania, School of Medicine and, Division of Genetics the Children's Hospital of Philadelphia.
Ania M FiksinskiDepartments of Pediatrics and Psychology, University Medical Center Utrecht, Utrecht, the Netherlands.
Jennifer K ForsythDepartment of Psychology, University of Washington, Seattle, WA, USA.
Marianna FrascarelliDepartment of Human Neurosciences, Sapienza University, Rome, Italy.
Wanda P FremontDepartment of Psychiatry and Behavioral Sciences, State University of New York at Upstate Medical University, Syracuse, NY, USA.
Maria GudbrandsenCentre for Research in Psychological Wellbeing (CREW), School of Psychology, University of Roehampton, London, UK.
Raquel E GurNeurodevelopment and Psychosis Section, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Joachim F HallmayerDepartment of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
Maria JalbrzikowskiDepartment of Psychiatry and Behavioral Sciences, Boston Children's Hospital, Boston, MA.
Wendy R KatesDepartment of Psychiatry and Behavioral Sciences, State University of New York at Upstate Medical University, Syracuse, NY, USA.
David E LindenCentre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
Kathryn L McCabeDepartment of Medicine and Public Health, University of Newcastle, Australia.
Donna M McDonald-McGinn22q and You Center and Division of Genetic and Genomic Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Declan MurphyInstitute of Psychiatry Psychology and Neuroscience, King's College London.
Kieran C MurphyDepartment of Psychiatry, Royal College of Surgeons in Ireland, Dublin, Ireland.
Ruth O'HaraDepartment of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
Michael J OwenCentre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
Allan L ReissDepartment of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford University, Stanford, CA, USA.
Gabriela M RepettoRare Diseases Program, Institute for Science and Innovation in Medicine, Facultad de Medicina Clinica Alemana Universidad del Desarrollo, Santiago, Chile.
David R RoalfDepartment of Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
Kosha RuparelNeurodevelopment and Psychosis Section, Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
J Eric SchmittDepartments of Radiology and Psychiatry, University of Pennsylvania, Philadelphia, PA, USA.
Sam A SievertsenDepartment of Psychology, University of Washington, Seattle, WA, USA.
Tony J SimonDepartment of Psychiatry and Behavioral Sciences and UC Davis MIND Institute, University of California Davis, Davis, CA, USA.
Zachary H TrevorrowDepartment of Psychology, University of Washington, Seattle, WA, USA.
Therese van AmelsvoortMental Health and Neuroscience Research Institute (MHeNs), Maastricht University, Maastricht, The Netherlands.
Marianne B M van den BreeCentre for Neuropsychiatric Genetics and Genomics, Division of Psychological Medicine and Clinical Neurosciences, Cardiff University, Cardiff, UK.
Jacob A S VorstmanDepartment of Psychiatry, The Hospital for Sick Children, Toronto, ON, Canada.
Elaine H Zackai22q and You Center and Division of Genetic and Genomic Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Christopher R K ChingImaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, University of Southern California, Los Angeles, CA, USA.
Paul M ThompsonImaging Genetics Center, Mark and Mary Stevens Neuroimaging and Informatics Institute, University of Southern California, Los Angeles, CA, USA.
Carrie E BeardenDepartment of Psychiatry and Biobehavioral Sciences, Semel Institute for Neuroscience and Human Behavior and Department of Psychology, University of California Los Angeles, Los Angeles, CA, USA.

Funding

Biomarkers for Psychosis in Velocardiofacial SyndromeR01MH064824 · NIMH · UPSTATE MEDICAL UNIVERSITY · PI KATES, WENDY · 2002 to 2015
$7.3M
Neurodevelopment and Psychosis in the 22q11.2 Deletion SyndromeR01MH085953 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BEARDEN, CARRIE E · 2010 to 2020
$6.2M
Visuospatial Cognitive Deficit in Del22q11.2 SyndromeR01HD042974 · NICHD · UNIVERSITY OF CALIFORNIA DAVIS · PI SIMON, TONY J · 2003 to 2013
$4.9M
Integrative Molecular and Phenotype Analysis of 22q11.2 Deletion SyndromeR01MH100900 · NIMH · STANFORD UNIVERSITY · PI HALLMAYER, JOACHIM F · 2013 to 2017
$4.8M
Olfactory and facial markers of developmental risk for psychosis in 22q11 deletion syndromeR01MH119185 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI ROALF, DAVID R · 2019 to 2024
$3.5M
ENIGMA World Aging CenterR01AG058854 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI THOMPSON, PAUL M · 2021 to 2025
$3.3M
1/9: Dissecting the effects of genomic variants on nenriched for neuropsychiatric disorderseurobehavioral dimensions in CNVs U01MH119738 · NIMH · UNIVERSITY OF PENNSYLVANIA · PI GUR, RAQUEL E · 2019 to 2023
$3.2M
Precision brain charts for imaging-genomics of schizophrenia and the psychosis spectrumR01MH133843 · NIMH · CHILDREN'S HOSP OF PHILADELPHIA · PI Aaron Felix Alexander-Bloch · 2023 to 2026
$3.2M
Molecular Dissection of the 22q11.2 Deletion SyndromeR01GM125757 · NIGMS · CHILDREN'S HOSP OF PHILADELPHIA · PI EMANUEL, BEVERLY S · 2018 to 2024
$3.1M
ENIGMA Bipolar Initiative: A Global Study of Imaging Genomics & Clinical OutcomesR01MH129742 · NIMH · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Christopher Ching, PAUL M THOMPSON · 2022 to 2026
$3.0M
Neurodevelopment and Psychosis in the 22q11.2 Copy Number VariantsR37MH085953 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI CARRIE E BEARDEN · 2023 to 2026
$2.9M
Global Deep Learning Initiative to Understand Outcomes in Major DepressionR01MH131806 · NIMH · UNIVERSITY OF SOUTHERN CALIFORNIA · PI Roberto Goya-Maldonado, PAUL M THOMPSON · 2023 to 2026
$2.6M
NIA NIH HHS R01 AG058854NIA NIH HHS T32 AG058507NICHD NIH HHS R01 HD042974NIDA NIH HHS F31 DA060068NIGMS NIH HHS R01 GM125757NIH HHS S10 OD032285NIMH NIH HHS R01 MH064824NIMH NIH HHS R01 MH085953NIMH NIH HHS R01 MH100900NIMH NIH HHS R01 MH119185NIMH NIH HHS R01 MH129742NIMH NIH HHS R01 MH129858NIMH NIH HHS R01 MH131806NIMH NIH HHS R01 MH133843NIMH NIH HHS R01 MH134962NIMH NIH HHS R01 MH134965NIMH NIH HHS R21 MH116473NIMH NIH HHS R21 MH139001NIMH NIH HHS R37 MH085953NIMH NIH HHS U01 MH101722NIMH NIH HHS U01 MH101724NIMH NIH HHS U01 MH119736NIMH NIH HHS U01 MH119737NIMH NIH HHS U01 MH119738NIMH NIH HHS U01 MH119758Wellcome Trust
6 · The paper itself

Abstract

Importance: 22q11.2 deletion syndrome (22q11DS) is among the strongest genetic risk factors for neuropsychiatric disorders and has marked effects on brain structure. Yet, it remains unclear which neuroanatomical features reflect uniform effects of the deletion versus inter-individual biological processes relevant to psychiatric outcomes. Identifying these features is critical for developing targeted treatments and interventions. Objective: To identify brain regions where 22q11DS exerts its most consistent and most variable impacts, and to test whether these patterns align with normative neurotransmitter receptor distributions and cortical growth trajectories. Design: Multisite cross-sectional case-control study. Setting: T1-weighted brain MRI data were obtained across 15 scanners. MRI data underwent standardized processing, quality control procedures and statistical site-adjustment using ComBat. Participants: A total of N = 438 individuals with 22q11DS (5-54 years, 48% females) and 380 typically developing controls (6-58 years, 48% females). Main Outcomes and Measures: Primary outcomes were global and regional cortical thickness and surface area. Mean and dispersion estimates were calculated using double generalized linear models, correcting for age, age Results: Compared with controls, individuals with 22q11DS showed widespread mean differences in cortical thickness and surface area. Notably, 22q11DS was associated with greater regional heterogeneity in both measures, except for reduced dispersion in the anterior cingulate. Effects were attenuated after covariate adjustment. Cortical thickness differences spatially overlapped with regions enriched for glutamatergic and GABAergic receptors. There was partial evidence linking surface area dispersion patterns to normative cortical growth trajectories. Conclusions and Relevance: 22q11DS exerts broad effects on cortical structure consistent with a global developmental mechanism, reflected in widespread mean shifts. Beyond these, region-specific variability, particularly in cortical thickness, suggests individualized neurobiological processes. The anterior cingulate emerges as a region of consistent structural deviation. Overall, structural variability in 22q11DS aligns with normative patterns of excitatory-inhibitory signaling and cortical development, implicating these pathways as potential targets for intervention.

Indexed as

22q11.2 deletion syndromecortical surface areacortical thicknessheterogeneity

Identifiers

PMID42238402
PMCPMC13228650

What Socratic holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.