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Background  Approximately 1 in 650 boys are born with an extra X chromosome. Boys and men with 47,XXY (Klinefelter syndrome) are at risk for neurodevelopmental disorders and specific cognitive impairments. This study was focused on social anxiety and social cognition. The aim was to assess if these aspects of the phenotype are related to testosterone deficiency, which is typically seen in 47,XXY from puberty onwards.    Methods  In the study 20 boys with 47,XXY and 25 non-clinical controls between 8 and 19 years participated. None had ever used testosterone supplements. Cognitive tests measuring the labeling of facial expressions and perspective taking (Theory of Mind) were administered. Self-report questionnaires were used to assess social anxiety. Testosterone was measured in saliva.    Results  Within the 47,XXY group lower levels of salivary testosterone were significantly associated with higher levels of social anxiety. The correlation was strong, andindependent of age and pubertal development. However, salivary levels of testosterone were uncorrelated to social cognitive skills.    Discussion  These findings point out that lower testosterone levels might contribute to high social anxiety in 47,XXY, suggesting that anxiety should be monitored in pubertal boys with XXY presenting with testosterone deficiency. This should be done in addition to exploring cognitive behavioral therapy or psychopharmacologic treatments targeting anxiety, which are more evidence based. In contrast, testosterone levels were not associated with social cognitive functioning, suggesting that other mechanisms are driving vulnerabilities in this domain.

Salivary testosterone in relation to social cognition and social anxiety in children and adolescents with 47,XXY (Klinefelter syndrome)