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

PMCID: PMC12180508

PMID: 40525963

DOI: 10.1017/S0033291725000765

Journal: Psychological medicine

Publication Date: 2025

Authors: Larsen IG, Liu S, Schaffer L, Rau S, Ajumobi T, et al.

Key Points

• Proactive aggression and social problems exhibit distinctly different correlation patterns between XXY/KS and XYY syndromes
• No statistically significant differences were found in the overall strength of psychopathology correlations between syndromes
• The study provides a generalizable analytic framework for comparing psychopathology architectures across different clinical groups

Summary

This groundbreaking study explores the architectural differences in psychopathology between two sex chromosome aneuploidy (SCA) syndromes: XXY/Klinefelter syndrome (KS) and XYY syndrome. By analyzing a comprehensive questionnaire battery across 300 individuals aged 5-25 years, researchers developed a novel analytic pipeline to compare the intricate correlations between 53 diverse psychopathology measures.

The research revealed nuanced differences in how psychiatric symptoms interconnect between XXY/KS and XYY syndromes. While the overall strength of symptom correlations remained similar, significant variations emerged in specific domains. XXY/KS demonstrated greater coherence among autism-related, internalizing, and externalizing features, whereas XYY syndrome showed stronger interconnectivity in attentional and motor control neurodevelopmental problems. These findings suggest the potential need for syndrome-specific clinical assessment and treatment approaches that account for unique genetic and neurological profiles.