Deep phenotypic analysis of psychiatric features in genetically defined cohorts: application to XYY syndrome

Journal of Neurodevelopmental Disorders

Research

Dani S. Bassett¹  Audrey Thurm²  Lisa Joseph²  Anastasia Xenophontos³  Siyuan Liu³  Ari M. Fish³  Catherine Mankiw³  Liv S. Clasen³  Armin Raznahan³  Luke Schaffer³  Jonathan D. Blumenthal³  Erin N. Torres³  Srishti Rau⁴ 

[1] Departments of Bioengineering, Electrical & Systems Engineering, Physics and Astronomy, Neurology and Psychiatry, University of Pennsylvania, Philadelphia, PA, USA;Santa Fe Institute, Santa Fe, NM, USA;Neurodevelopmental and Behavioral Phenotyping Service, Office of the Clinical Director, National Institute of Mental Health Intramural Research Program, Bethesda, MD, USA;Section On Developmental Neurogenomics, Human Genetics Branch, National Institute of Mental Health Intramural Research Program, 20892, Bethesda, MD, USA;Section On Developmental Neurogenomics, Human Genetics Branch, National Institute of Mental Health Intramural Research Program, 20892, Bethesda, MD, USA;Center for Autism Spectrum Disorders and Division of Neuropsychology, Children’s National Health System, Washington, DC, USA;

关键词: Behavioral phenotyping;    Neurogenetics;    Symptom networks;    Sex chromosomes;    Deep phenotyping;    Adaptive function;   

DOI  :  10.1186/s11689-023-09476-y

 received in 2022-09-02, accepted in 2023-01-27,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundRecurrent gene dosage disorders impart substantial risk for psychopathology. Yet, understanding that risk is hampered by complex presentations that challenge classical diagnostic systems. Here, we present a suite of generalizable analytic approaches for parsing this clinical complexity, which we illustrate through application to XYY syndrome.MethodWe gathered high-dimensional measures of psychopathology in 64 XYY individuals and 60 XY controls, plus additional interviewer-based diagnostic data in the XYY group. We provide the first comprehensive diagnostic description of psychiatric morbidity in XYY syndrome and show how diagnostic morbidity relates to functioning, subthreshold symptoms, and ascertainment bias. We then map behavioral vulnerabilities and resilience across 67 behavioral dimensions before borrowing techniques from network science to resolve the mesoscale architecture of these dimensions and links to observable functional outcomes.ResultsCarriage of an extra Y-chromosome increases risk for diverse psychiatric diagnoses, with clinically impactful subthreshold symptomatology. Highest rates are seen for neurodevelopmental and affective disorders. A lower bound of < 25% of carriers are free of any diagnosis. Dimensional analysis of 67 scales details the profile of psychopathology in XYY, which survives control for ascertainment bias, specifies attentional and social domains as the most impacted, and refutes stigmatizing historical associations between XYY and violence. Network modeling compresses all measured symptom scales into 8 modules with dissociable links to cognitive ability, adaptive function, and caregiver strain. Hub modules offer efficient proxies for the full symptom network.ConclusionsThis study parses the complex behavioral phenotype of XYY syndrome by applying new and generalizable analytic approaches for analysis of deep-phenotypic psychiatric data in neurogenetic disorders.

【 授权许可】

CC BY   
© This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023

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