Brain and Behavior during Puberty in Klinefelter Syndrome.

Klinefelter综合征(KS)是一种高度流行的性染色体非整倍体，其特征是 表型男性X染色体(47，XXY)数目增加。尽管它经常发生(高达1年 500名男性出生)，临床医生通常对认知行为障碍的诊断或处理知之甚少 以及KS的社交情绪症状，其中可能包括基于语言的学习障碍， 执行功能和社交技能，以及抑郁和焦虑症状的增加。子女的父母 与通常观察到的相比，KS经常报告对这些行为障碍的更多担忧 KS的身体特征(例如，高个子和睾丸衰竭)，因为它们有可能影响日常生活 在家庭和学校发挥作用，并可能对长期的社会和职业成果产生负面影响。 大多数患有KS的男性首先出现睾丸功能衰竭(即睾丸激素缺乏和/或性腺功能减退 症状)从青春期中期开始。出于这个原因，儿科内分泌科医生通常会开出睾丸素。 大约在这个时候开始替代疗法(TRT)。然而，在知识和知识方面仍然存在很大差距 关于这种治疗对男性KS患者神经和行为发育影响的基本问题， 尽管睾丸激素对大脑和认知的影响已经得到了很好的证明，但通常是发育中的男性。 这里提出的前瞻性、纵向、多时间点研究将是第一次评估 TRT是否存在(即睾丸衰竭)对青少年大脑发育和行为的影响 KS使用多层次的分析(认知-行为和社会-情感功能，多模式 成像、青春期状态、荷尔蒙水平)。70名患有KS的男孩和58岁智商的对照组-- 匹配的8到17岁的神经典型男孩将被招募，并每年跟踪调查最多 三年了。三个具体目标将被解决：(1)检查TRT对执行功能的影响和 KS患者的社会情绪症状(2)评估TRT对KS患者脑结构和功能的影响 目的：阐明KS(探索性)中的脑行为关联。我们还将研究 严重程度、睾丸衰竭、脑和行为测量。 我们建议的多学科研究提供了一个首创的机会，以提供更多的 TRT对KS男童认知、行为和情绪影响的研究 青春期周围的时期。这项研究的结果旨在引导改进临床的发展。 KS男童认知行为和社会情绪症状的管理 关于男性青春期认知、行为和情绪的神经变化的常识。

Klinefelter syndrome (KS) is a highly prevalent sex chromosome aneuploidy that is characterized by an increased number of X chromosomes (47,XXY) in phenotypic males. Despite its frequent occurrence (up to 1 in 500 male births), clinicians often have little awareness about the diagnosis or management of cognitive-behavioral and social-emotional symptoms of KS, which can include impairments in language-based learning, deficits in executive functioning and social skills, and increased symptoms of depression and anxiety. Parents of children with KS often report greater concerns about these behavioral disturbances relative to commonly observed physical features in KS (e.g., tall stature and testicular failure), since they have the potential to affect everyday function at home and at school, and can negatively influence long term social and vocational outcomes. Most males with KS first experience testicular failure (i.e., deficiency in testosterone and/or hypogonadal symptoms) starting in mid-puberty. For this reason, pediatric endocrinologists typically prescribe testosterone replacement therapy (TRT) starting around this time. However, there remain large gaps in knowledge and fundamental questions about the effects of this treatment on neural and behavioral development in males with KS, despite well-documented effects of testosterone on the brain and cognition in typically developing males. The prospective, longitudinal, multi-time point research proposed here would be the first to assess the effects of TRT, or lack thereof (i.e., testicular failure) on the development of the brain and behavior in adolescents with KS using multiple levels of analysis (cognitive-behavioral and social-emotional functioning, multi-modal imaging, pubertal status, hormone levels). Seventy boys with KS and a comparison group of 58 age- and IQ- matched neurotypical boys between the ages of 8 and 17 years will be recruited and followed annually for up to three years. Three specific aims will be addressed: (1) to examine the effects of TRT on executive function and social-emotional symptoms in KS (2) to evaluate the effects of TRT on brain structure and function in KS and, (3) to elucidate brain-behavior associations in KS (exploratory). We will also examine associations between the severity testicular failure and brain and behavioral measures. The multidisciplinary research we propose offers a first-of-its-kind opportunity to provide an increased understanding of how TRT exerts its beneficial effect on cognition, behavior and mood in boys with KS during the peripubertal period. The results of this study are intended to lead to the development of improved clinical management of cognitive-behavioral and social-emotional symptoms in boys with KS while advancing our general knowledge of neural changes underlying cognition, behavior and mood during male puberty.