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Record W3093118262 · doi:10.1038/s41467-020-18997-2

Mutations associated with neuropsychiatric conditions delineate functional brain connectivity dimensions contributing to autism and schizophrenia

2020· article· en· W3093118262 on OpenAlexafffund
Clara Moreau, Sebastian Urchs, Kuldeep Kumar, Pierre Orban, Catherine Schramm, Guillaume Dumas, Aurélie Labbe, Guillaume Huguet, Élise Douard, Pierre-Olivier Quirion, Amy Lin, Leila Kushan, Stéphanie Grot, David Luck, Adrianna Mendrek, Stéphane Potvin, Émmanuel Stip, Thomas Bourgeron, Alan C. Evans, Carrie E. Bearden, Pierre Bellec, Sébastien Jacquemont

Bibliographic record

VenueNature Communications · 2020
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCongenital heart defects research
Canadian institutionsMcGill UniversityBishop's UniversityMcGill University and Génome Québec Innovation CentreHEC MontréalJewish General HospitalUniversité de MontréalInstitut Universitaire en Santé Mentale de QuébecMontreal Neurological Institute and HospitalInstitut Universitaire de Gériatrie de MontréalCentre Hospitalier Universitaire Sainte-Justine
FundersNIH Clinical CenterNational Center for Research ResourcesNational Institute of Dental and Craniofacial ResearchCanadian Institutes of Health ResearchNational Institute of Biomedical Imaging and BioengineeringFonds de Recherche du Québec - SantéSimons Foundation Autism Research InitiativeFondation Brain CanadaU.S. National Library of MedicineNational Institute of Neurological Disorders and StrokeNational Institute of General Medical SciencesUniversity of MinnesotaMassachusetts General HospitalSimons FoundationCompute CanadaNational Institute of Mental HealthNorthwestern UniversityCourtois FoundationLeon Levy FoundationNational Institutes of HealthCanada First Research Excellence FundU.S. Department of Health and Human ServicesNational Institute on Drug AbuseInstitut de Valorisation des DonnéesStavros Niarchos FoundationU.S. Department of Energy
KeywordsSchizophrenia (object-oriented programming)Copy-number variationFunctional magnetic resonance imagingAutism spectrum disorderAutismNeuroscienceInsulaAttention deficit hyperactivity disorderThalamusAffect (linguistics)CognitionResting state fMRIPsychologyGeneticsBiologyPsychiatryGeneGenome

Abstract

fetched live from OpenAlex

16p11.2 and 22q11.2 Copy Number Variants (CNVs) confer high risk for Autism Spectrum Disorder (ASD), schizophrenia (SZ), and Attention-Deficit-Hyperactivity-Disorder (ADHD), but their impact on functional connectivity (FC) remains unclear. Here we report an analysis of resting-state FC using magnetic resonance imaging data from 101 CNV carriers, 755 individuals with idiopathic ASD, SZ, or ADHD and 1,072 controls. We characterize CNV FC-signatures and use them to identify dimensions contributing to complex idiopathic conditions. CNVs have large mirror effects on FC at the global and regional level. Thalamus, somatomotor, and posterior insula regions play a critical role in dysconnectivity shared across deletions, duplications, idiopathic ASD, SZ but not ADHD. Individuals with higher similarity to deletion FC-signatures exhibit worse cognitive and behavioral symptoms. Deletion similarities identified at the connectivity level could be related to the redundant associations observed genome-wide between gene expression spatial patterns and FC-signatures. Results may explain why many CNVs affect a similar range of neuropsychiatric symptoms.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.002
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.845
Threshold uncertainty score0.635

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.002
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0010.000
Scholarly communication0.0000.000
Open science0.0000.001
Research integrity0.0000.001
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.019
GPT teacher head0.300
Teacher spread0.281 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designObservational
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations66
Published2020
Admission routes2
Has abstractyes

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