Executive Dysfunction in Klinefelter Syndrome: Associations With Brain Activation and Testicular Failure

作者：Lara C. Foland‐Ross, Elnaz Ghasemi, Vanessa Lozano Wun, Tandy Aye, Karen Kowal, Judith L. Ross, Allan L. Reiss · 发表于：The Journal of Clinical Endocrinology & Metabolism · 年份：2023 · DOI：10.1210/clinem/dgad487 · 被引用次数：10 · 研究领域：Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities、Hypothalamic control of reproductive hormones、Sexual Differentiation and Disorders

CONTEXT: Executive dysfunction is a well-recognized component of the cognitive phenotype of Klinefelter syndrome (KS), yet the neural basis of KS-associated cognitive weaknesses, and their association with testicular failure is unknown. OBJECTIVE: We investigated executive function, brain activation, and pubertal development in adolescents with and without KS. METHODS: Forty-three adolescents with KS (mean age 12.3 ± 2.3 years) and 41 typically developing boys (mean age 11.9 ± 1.8 years) underwent pubertal evaluation, behavioral assessment, and completed functional magnetic resonance imaging (fMRI) as they performed an executive function task, the go/no-go task. Group differences in activation were examined. Associations among activation, executive function, and pubertal development measures were tested in secondary analyses. RESULTS: Boys with KS exhibited reduced executive function, as well as lower activation in brain regions subserving executive function, including the inferior frontal gyrus, anterior insula, dorsal anterior cingulate cortex, and caudate nucleus. Secondary analyses indicated that the magnitude of activation differences in boys with KS was associated with severity of pubertal developmental delay, as indexed by lower testosterone (t(36) = 2.285; P = .028) and lower testes volume (t(36) = 2.238; P = .031). Greater parent-reported attention difficulties were additionally associated with lower testicular volume (t(36) = -2.028; P = .050). CONCLUSION: These fin...