Brain and Behavior during Puberty in Klinefelter Syndrome

克兰费尔特综合征青春期的大脑和行为

• 批准号: 9766339
• 负责人: Allan L Reiss
• 金额: $ 62.38万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-17 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9766339
• 关键词: Address; Adolescent; Affect; Affective; Age; Amygdaloid structure; Anterior; Anxiety; Attention; Attention deficit hyperactivity disorder; Awareness; Base of the Brain; Behavior; Behavioral; Birth; Brain; Characteristics; Child; Childhood; Clinical; Clinical Management; Cognition; Cognitive; Collaborations; Coupled; Development; Diagnosis; Diffusion Magnetic Resonance Imaging; Dose; Emotional; Emotions; Endocrinologist; Executive Dysfunction; Exhibits; Failure; Functional Magnetic Resonance Imaging; Genetic Diseases; Goals; Gonadal Steroid Hormones; Gynecomastia; Home environment; Hormonal; Hormones; Impairment; Individual; Inferior frontal gyrus; Insula of Reil; Interdisciplinary Study; Investigation; Klinefelter' s Syndrome; Knowledge; Language; Language Development; Lead; Learning Disabilities; Literature; Mental Depression; Moods; Multimodal Imaging; Neurophysiology - biologic function; Outcome; Parents; Pattern; Phenotype; Principal Investigator; Psyche structure; Psychosocial Assessment and Care; Puberty; Reporting; Research; Research Personnel; Sampling; Schools; Severities; Spermatogenesis; Structure; Supplementation; Symptoms; Syndrome; Testing; Testosterone; Time; Variant; X Chromosome; anxiety symptoms; base; behavior measurement; boys; brain behavior; cingulate cortex; cognitive ability; cognitive development; cognitive testing; comparison group; depressive symptoms; emotional symptom; executive function; experience; flexibility; improved; male; neural circuit; novel; peripubertal period; physical symptom; prepuberty; prospective; recruit; relating to nervous system; secondary analysis; sex chromosome aneuploidy; social; social skills; standard care; testosterone replacement therapy

Klinefelter syndrome (KS) is a highly prevalent sex chromosome aneuploidy syndrome 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 relatively little awareness about diagnosis or management of cognitive-behavioral and social-emotional problems in boys with KS. These problems can include significant language-based learning disability, executive function deficits and ADHD symptoms, impaired social skills, depression and anxiety. Parents of children with KS often report greater concerns about these brain-based disturbances relative to commonly observed physical symptoms in KS such as tall stature and testicular failure, since they have the potential to affect everyday function at home and school, and long- term social and vocational outcome. Most boys with KS experience testicular insufficiency (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 in the pubertal period. However, there remain large gaps in knowledge and fundamental questions about the effects of TRT on brain development and function in KS. Indeed, a wide body of literature indicates that the rise in testosterone at puberty in typically developing boys influences a wave of neural remodeling, and that these changes in neural circuitry are tightly coupled with changes in cognition, behavior and mood. The prospective, longitudinal, multi-time point research proposed here would be the first to assess the effects of TRT on brain development and function in adolescents with KS using multiple levels of analysis (cognitive-behavioral and social-emotional functioning, multi-modal imaging, pubertal status, hormone levels). Sixty boys with KS and a comparison group of 60 age- and IQ-matched neurotypical boys between the ages of 9 and 13 years will be recruited and followed annually for up to four 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 severity of testicular insufficiency as a modifier of brain and behavioral measures in secondary analyses. 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.

KlineFelter综合征（KS）是一种高度普遍的性染色体非整倍性综合征 特征是表型雄性中X染色体数量增加（47，XXY）。尽管经常 发生（最多只有500名男性出生），临床医生通常对诊断或 KS男孩的认知行为和社会情感问题的管理。这些问题可以 包括重要的基于语言的学习障碍，执行功能缺陷和多动症症状， 社交技能，抑郁和焦虑症受损。 KS儿童的父母经常报告对 这些基于大脑的障碍相对于KS等常见的身体症状，例如高个子 和睾丸故障，因为它们有可能影响家庭和学校的日常功能，并且长期 术语社会和职业结果。 大多数具有KS的男孩经历睾丸功能不全（即睾丸激素缺乏和/或性疾病 症状）从中期开始。因此，儿科内分泌学家通常会开处方睾丸激素 从青春期开始的替代疗法（TRT）。但是，知识和 关于TRT对KS脑发育和功能的影响的基本问题。确实，宽阔的身体 文献表明，典型开发男孩的青春期睾丸激素的增加会影响一波 神经重塑，并且神经回路中的这些变化与认知的变化紧密相结合， 行为和心情。 这里提出的前瞻性，纵向，多时间研究将是第一个评估 TRT使用多个分析的KS青少年对大脑发育和功能的影响 （认知行为和社会情感功能，多模式成像，青春期状态，激素水平）。 60名具有KS的男孩和一个60岁和IQ匹配的神经型男孩的比较组 9年和13年将被招募并每年紧随其后长达四年。三个具体目标将是 解决：（1）检查TRT对KS（2）中执行功能和社会情感症状的影响 评估TRT对KS大脑结构和功能的影响以及（3）阐明脑行为 KS的协会（探索性）。我们还将检查睾丸不足作为大脑修饰符的严重程度 和二级分析中的行为度量。 我们提出的多学科研究提供了首要机会，以提供增加 了解TRT如何对具有KS的男孩的认知，行为和情绪施加有益作用 腹部时期。这项研究的结果旨在导致临床改善的发展 在推进我们的KS男孩的认知行为和社会情感症状的管理同时 对男性青春期期间的认知，行为和情绪的神经变化的一般知识。