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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

基本信息

批准号：
10430045
负责人：
Allan L Reiss
金额：
$ 61.14万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-17 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10430045
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 Hormonal Hormones Impairment Individual Inferior frontal gyrus Insula of Reil Interdisciplinary Study Investigation Klinefelter&apos 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 Social Functioning 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 functioning 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

项目摘要

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）是一种非常普遍的性染色体非整倍体综合征