Evidence map›Paper›PMID 40525963›Full record

ArticlePsychological medicine2025

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

Isabella G Larsen, Siyuan Liu, Lukas Schaffer, Srishti Rau, Tiffany Ajumobi, Bridget W Mahony, Allysa Warling, Ethan T Whitman, Ajay Nadig, Cassidy McDermott and 7 more

Abstract readComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Article in Psychological medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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

What it found

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2 · The registry

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

17 authors.

Isabella G LarsenSection on Developmental Neurogenomics, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.ORCID 0000-0001-8520-5539
Siyuan LiuSection on Developmental Neurogenomics, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
Lukas SchafferInstitute for Behavioral Genetics, University of Colorado Boulder, Boulder, CO, USA.
Srishti RauCenter for Autism Spectrum Disorders, Children's National Hospital, Washington, DC, USA.
Tiffany AjumobiSchool of Medicine, The Johns Hopkins University, Baltimore, MD, USA.
Bridget W MahonyInternational Consulting Associates, Inc, Arlington, VA, USA.
Allysa WarlingHarvard Medical School, Boston, MA, USA.
Ethan T WhitmanDepartment of Psychology & Neuroscience, Duke University, Durham, NC, USA.
Ajay NadigDepartment of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
Cassidy McDermottDepartment of Psychology, University of Pennsylvania, Philadelphia, PA, USA.
Anastasia XenophontosGeorgetown University School of Medicine, Washington, DC, USA.
Kathleen WilsonDepartment of Psychiatry, University of Michigan, Ann Arbor, MI, USA.
Liv S ClasenSection on Developmental Neurogenomics, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
Erin N TorresSection on Developmental Neurogenomics, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
Jonathan D BlumenthalSection on Developmental Neurogenomics, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
Dani S BassettDepartment of Bioengineering, School of Engineering and Applied Science, University of Pennsylvania, Philadelphia, PA, USA.
Armin RaznahanSection on Developmental Neurogenomics, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.

Funding

Medical Scientist Training ProgramT32GM144273 · NIGMS · HARVARD MEDICAL SCHOOL · PI David Shumway Jones, Jacqueline A. Lees · 2022 to 2026
$14.7M
NIGMS NIH HHS T32 GM144273
6 · The paper itself

Abstract

backgroundPsychiatric 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.

methodsWe use a large questionnaire battery in 300 individuals aged 5-25 years (

resultsBehavior 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.

conclusionsThese 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.

Indexed as

AneuploidyChromosomes, Human, XChromosomes, Human, YKlinefelter SyndromeMental DisordersXYY KaryotypeAdolescentAdultChildChild, PreschoolHumansMalePsychopathologyYoung Adultbehavioral phenotypinggene dosage disordersJacobs syndromeKlinefelter syndromesex chromosome aneuploidysymptom network analysisXXY/KSXYY

Identifiers

PMID40525963
PMCPMC12180508

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