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Mapping Subcortical Brain Alterations in 22q11.2 Deletion Syndrome: Effects of Deletion Size and Convergence With Idiopathic Neuropsychiatric Illness

2020· article· en· W3006118472 on OpenAlexfundno aff
Christopher R. K. Ching, Boris A. Gutman, Daqiang Sun, Julio E. Villalón‐Reina, Anjanibhargavi Ragothaman, Dmitry Isaev, Artemis Zavaliangos‐Petropulu, Amy Lin, Rachel K. Jonas, Leila Kushan, Laura Pacheco-Hansen, Ariana Vajdi, Jennifer K. Forsyth, Maria Jalbrzikowski, Geor Bakker, Thérèse van Amelsvoort, Kevin M. Antshel, Wanda Fremont, Wendy R. Kates, Linda Campbell, Kathryn McCabe, Michael Craig, Eileen Daly, Maria Gudbrandsen, Clodagh M. Murphy, Declan Murphy, Kieran C. Murphy, Ania Fiksinski, Sanne Koops, Jacob Vorstman, T. Blaine Crowley, Beverly S. Emanuel, Raquel E. Gur, Donna M. McDonald‐McGinn, David R. Roalf, Kosha Ruparel, J. Eric Schmitt, Elaine H. Zackai, Courtney A. Durdle, Naomi J. Goodrich‐Hunsaker, Tony J. Simon, Anne S. Bassett, Nancy J. Butcher, Eva W.C. Chow, Fidel Vila‐Rodriguez, Adam Cunningham, Joanne Doherty, David E.J. Linden, Hayley Moss, Michael J. Owen, Marianne B. M. van den Bree, Nicolás Crossley, Gabriela M. Repetto, Paul M. Thompson, Carrie E. Bearden

Bibliographic record

VenueAmerican Journal of Psychiatry · 2020
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCongenital heart defects research
Canadian institutionsnot available
FundersNational Institute of Mental HealthNational Institute for Health and Care ResearchNational Institute on AgingWellcome TrustComisión Nacional de Investigación Científica y TecnológicaNational Institute of Biomedical Imaging and BioengineeringCanadian Institutes of Health ResearchSouth London and Maudsley NHS Foundation TrustNational Institute of Child Health and Human DevelopmentNIHR Maudsley Biomedical Research CentreNational Institutes of HealthChildren's Hospital of PhiladelphiaKing's College LondonNational Institute of General Medical SciencesFondation Brain CanadaMichael Smith Health Research BCEunice Kennedy Shriver National Institute of Child Health and Human DevelopmentArbor PharmaceuticalsNational Alliance for Research on Schizophrenia and DepressionMedical Research CouncilBiogenUniversity of OxfordVancouver Coastal Health Research InstituteUniversity of Pennsylvania
KeywordsPutamenPsychosisThalamusPsychologyNeuroimagingSchizophrenia (object-oriented programming)AmygdalaHippocampusNeuroscienceInternal medicineMedicinePsychiatry

Abstract

fetched live from OpenAlex

OBJECTIVE: 22q11.2 deletion syndrome (22q11DS) is among the strongest known genetic risk factors for schizophrenia. Previous studies have reported variable alterations in subcortical brain structures in 22q11DS. To better characterize subcortical alterations in 22q11DS, including modulating effects of clinical and genetic heterogeneity, the authors studied a large multicenter neuroimaging cohort from the ENIGMA 22q11.2 Deletion Syndrome Working Group. METHODS: Subcortical structures were measured using harmonized protocols for gross volume and subcortical shape morphometry in 533 individuals with 22q11DS and 330 matched healthy control subjects (age range, 6-56 years; 49% female). RESULTS: Compared with the control group, the 22q11DS group showed lower intracranial volume (ICV) and thalamus, putamen, hippocampus, and amygdala volumes and greater lateral ventricle, caudate, and accumbens volumes (Cohen's d values, -0.90 to 0.93). Shape analysis revealed complex differences in the 22q11DS group across all structures. The larger A-D deletion was associated with more extensive shape alterations compared with the smaller A-B deletion. Participants with 22q11DS with psychosis showed lower ICV and hippocampus, amygdala, and thalamus volumes (Cohen's d values, -0.91 to 0.53) compared with participants with 22q11DS without psychosis. Shape analysis revealed lower thickness and surface area across subregions of these structures. Compared with subcortical findings from other neuropsychiatric disorders studied by the ENIGMA consortium, significant convergence was observed between participants with 22q11DS with psychosis and participants with schizophrenia, bipolar disorder, major depressive disorder, and obsessive-compulsive disorder. CONCLUSIONS: In the largest neuroimaging study of 22q11DS to date, the authors found widespread alterations to subcortical brain structures, which were affected by deletion size and psychotic illness. Findings indicate significant overlap between 22q11DS-associated psychosis, idiopathic schizophrenia, and other severe neuropsychiatric illnesses.

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 machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.001
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Observational · Consensus signal: Observational
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.005

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0010.002
Meta-epidemiology (narrow)0.0010.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0010.000
Science and technology studies0.0000.001
Scholarly communication0.0000.000
Open science0.0000.001
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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 head0.004
GPT teacher head0.234
Teacher spread0.230 · 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 source (direct Gemma or distilled Codex), 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".

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Citations87
Published2020
Admission routes1
Has abstractyes

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