MétaCan
Menu
Back to cohort
Record W4411373268 · doi:10.1017/s0033291725000765

Novel tools for comparing the architecture of psychopathology between neurogenetic disorders: An application to X- versus Y-chromosome aneuploidy effects in males

2025· article· en· W4411373268 on OpenAlexaff
Isabella G Larsen, Siyuan Liu, Lukas Schaffer, Srishti Rau, Tiffany Ajumobi, Bridget W. Mahony, Allysa Warling, Ethan T. Whitman, Ajay Nadig, Cassidy L. McDermott, Anastasia Xenophontos, Kathleen Wilson, Liv Clasen, Erin Torres, Jonathan D. Blumenthal, Dani S. Bassett, Armin Raznahan

Bibliographic record

VenuePsychological Medicine · 2025
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicGenetic Associations and Epidemiology
Canadian institutionsMcGill UniversityMontreal Neurological Institute and Hospital
FundersNational Institute of General Medical SciencesNational Institute of Mental HealthNational Institutes of Health
KeywordsPsychopathologyPsychologyAutismGenetic architectureClinical psychologyAneuploidyPsychiatryGeneticsChromosomeBiologyGene

Abstract

fetched live from OpenAlex

BACKGROUND: Psychiatric symptoms are typically highly inter-correlated at the group level. Collectively, these correlations define the architecture of psychopathology - informing taxonomic and mechanistic models in psychiatry. However, to date, it remains unclear if this architecture differs between etiologically distinct subgroups, despite the core relevance of this understanding for personalized medicine. Here, we introduce a new analytic pipeline to probe group differences in the psychopathology architecture - demonstrated through the comparison of two distinct neurogenetic disorders. METHODS: = 134 age-matched XY) to characterize the structure of correlations among 53 diverse measures of psychopathology in XXY/KS and XYY syndrome - enabling us to compare the effects of X- versus Y-chromosome dosage on the architecture of psychopathology at multiple, distinctly informative levels. RESULTS: Behavior correlation matrices describe the architecture of psychopathology in each syndrome. A comparison of matrix rows reveals that social problems and externalizing symptoms are most differentially coupled to other aspects of psychopathology in XXY/KS versus XYY. Clustering the difference between matrices captures coordinated group differences in pairwise coupling between measures of psychopathology: XXY/KS shows greater coherence among externalizing, internalizing, and autism-related features, while XYY syndrome shows greater coherence in dissociality and early neurodevelopmental impairment. CONCLUSIONS: These methods offer new insights into X- and Y-chromosome dosage effects on behavior, and our shared code can now be applied to other clinical groups of interest - helping to hone mechanistic models and inform the tailoring of care.

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)0.001
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 score0.770
Threshold uncertainty score0.403

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
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 head0.043
GPT teacher head0.372
Teacher spread0.329 · 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

Citations2
Published2025
Admission routes1
Has abstractyes

Explore more

Same venuePsychological MedicineSame topicGenetic Associations and EpidemiologyFrench-language works237,207