Observational studyEuropean child & adolescent psychiatry2025
Associations between brain network, puberty, and behaviors in boys with Klinefelter syndrome.
Observational study in European child & adolescent psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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Who cites it
2 citing papers in PubMed.
- Growing up with Klinefelter syndrome: challenges of care in children and adolescents and patients advocacy.Endocrine · 2026Review
- Update on Physical, Psychological, and Quality of Life Management in Klinefelter Syndrome.The Journal of clinical endocrinology and metabolism · 2025Review
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
backgroundKlinefelter syndrome (KS), also referred to as XXY syndrome, is a significant but inadequately studied risk factor for neuropsychiatric disability. Whether alterations in functional brain connectivity or pubertal delays are associated with aberrant cognitive-behavioral outcomes in individuals with KS is largely unknown. In this observational study, we investigated KS-related alterations in the resting-state brain network, testosterone level, and cognitive-behavioral impairment in adolescents with Klinefelter syndrome.
methodsWe recruited 46 boys with KS, ages 8 to 17 years, and 51 age-matched typically developing (TD) boys. All participants underwent resting-state functional magnetic resonance imaging scans, pubertal, and cognitive-behavioral assessments. Resting-state functional connectivity and regional brain activity of the participants were assessed.
resultsWe found widespread alterations in global functional connectivity among the inferior frontal gyrus, temporal-parietal area, and hippocampus in boys with KS. Aberrant regional activities, including enhanced fALFF in the motor area and reduced ReHo in the caudate, were also found in the KS group compared to the TD children. Further, using machine learning methods, brain network alterations in these regions accurately differentiated boys with KS from TD controls. Finally, we showed that the alterations of brain network properties not only effectively predict cognitive-behavioral impairment in boys with KS, but also appear to mediate the association between total testosterone level and language ability, a cognitive domain at particular risk for dysfunction in this condition.
conclusionOur results offer an informatic neurobiological foundation for understanding cognitive-behavioral impairments in individuals with KS and contribute to our understanding of the interplay between pubertal status, brain function, and cognitive-behavioral outcome in this population.
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