Vulnerability for psychopathology in Klinefelter syndrome: age-specific and cognitive-specific risk profiles

Aim: Studying Klinefelter syndrome (KS) (47,XXY) can reveal insights into mechanisms of neurodevelopment. Our aim was to identify factors that influence risk for psychopathology in this syndrome, with a focus on age-specific and cognitive-specific risk profiles. Methods: A total of 73 subjects with KS (25 children and 48 adults) and 93 age-matched controls (53 children and 40 adults) participated in the study. The discrepancy between verbal IQ (VIQ) and performance IQ (PIQ) was assessed using the Wechsler Intelligence Scales. IQ data were only measured in the Klinefelter group. All participants completed the Autism Questionnaire and Schizotypal Personality Questionnaire. Results: Increased levels of autism traits and schizotypal traits were observed in individuals with KS, with schizotypal traits increasing with age. The VIQ < PIQ group (n = 33) showed significantly increased levels of autism traits compared to the PIQ < VIQ group (n = 12) and controls. The PIQ < VIQ group showed significantly increased levels of schizotypal traits compared to the VIQ < PIQ group and controls. The VIQ-PIQ discrepancy significantly correlated with schizotypal traits and autism traits, in opposite directions. Conclusion: Risk for psychopathology in KS may be age specific as well as dependent on cognitive profile. Relative deficits in verbal abilities seem more strongly associated with increased autism traits, whereas relative deficits in visuospatial abilities seem more strongly associated with increased schizotypal traits.