Brain Development & Sex Chromosomes: Imaging of Turner and Klinefelter Syndromes

大脑发育

基本信息

批准号：
8443566
负责人：
Allan L Reiss
金额：
$ 23.55万
依托单位：
STANFORD UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-04-18 至 2015-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8443566
关键词：
Academic achievement Additional X Chromosome Affect Age Amygdaloid structure Aneuploidy Area Attention Attention deficit hyperactivity disorder Autistic Disorder Behavior Behavioral Brain Child Childhood Chromosome Deletion Chromosomes, Human, Pair 2 Clinical Clinical Treatment Cognition Cognitive Cohort Studies Control Groups Corpus striatum structure Development Diagnosis Diffusion weighted imaging Disease Emotions Employee Strikes Face Female Gene Expression Genotype Goals Gonadal Steroid Hormones Hereditary Disease Human Image Impairment Individual Investigation Klinefelter&apos s Syndrome Laboratories Language Learning Disorders Literature Magnetic Resonance Imaging Measures Mental disorders Nature Neuroanatomy Neurophysiology - biologic function Occipital lobe Outcome Parietal Pathway interactions Pattern Performance Phenotype Population Prefrontal Cortex Process Production Relative (related person)Research Research Design Risk Role Secondary to Sex Characteristics Sex Chromosomes Structure Symptoms Temporal Lobe Testing Time Tissue-Specific Gene Expression Turner&apos s Syndrome Variant Visuospatial X Chromosome behavioral impairment boys brain behavior brain morphology brain volume clinical Diagnosis cohort dosage executive function girls improved insight male neurodevelopment neuroimaging neuropsychiatry prepuberty prospective public health relevance relating to nervous system resilience sex sexual dimorphism skills social cognition white matter

项目摘要

DESCRIPTION (provided by applicant): Sex differences in rates and manifestations of mental illness have been receiving increasing attention for their potential to inform diagnosis, clinical course and treatment in a broad range of neuropsychiatric disorders. Recent literature suggests that underlying mechanisms for these sex dimorphisms arise from: (1) differential expression of genes on the sex chromosomes and, (2) extensive influence of sex hormones on the brain during critical windows of development. Though the independent and interactive effect of these influences on brain development and function are thought to contribute significantly to sexually dimorphic patterns of cognition and behavior, research in this area is limited. Further investigation is essential to increase our understanding of how sex chromosome gene expression and sex hormone exposure influence neural processes underlying sex differences in both typical development and in mental illness. Sex chromosome aneuploidies such as Turner syndrome ('TS', 45,X) and Klinefelter syndrome ('KS', 47,XXY) represent unique paradigms for elucidating the influences of sex chromosome gene expression and sex hormone exposure on neural development and function. Each condition is characterized by an abnormal number of X chromosomes and affected (genotypic non-mosaic) individuals typically demonstrate greatly reduced levels of sex hormone production. Because TS and KS are associated with specific profiles of neuroanatomical and cognitive-behavioral variation, the study of these conditions can potentially provide unique information about sexually dimorphic brain differences occurring in typical development (where males have 46,XY genotype and females have 46,XX genotype). Although TS and KS have been previously studied independently, there has been no prospective, direct comparison of these cohorts to date, and no studies have compared these groups singly or together to both typically developing male and female cohorts. Here we describe a first-of-its-kind study designed to directly examine differences in neuroanatomy and cognitive-behavioral function between prepubertal, age-matched cohorts of girls with TS, boys with KS and typically developing male and female controls. The proposed project builds on striking observations from previous research conducted by our group and others suggesting that spatial patterns of neuroanatomical variation in TS and KS may be largely complementary relative to typical development. The cross-sectional investigation we propose would be the first to directly compare TS and KS in the same study with the goal of elucidating the early (prepubertal) effects of varying sex chromosome gene expression and associated sex hormone exposure on neuroanatomy. This research holds great promise for improving our understanding of sex chromosome gene expression and sex hormone effects on neurodevelopment in young children and correspondingly, and for providing new insights into neural processes underlying sex differences related to risk and resilience for mental illness.

描述（由申请人提供）：精神疾病率和表现的性别差异一直受到越来越多的关注，因为它们在广泛的神经精神疾病中为诊断，临床课程和治疗提供了信息。最近的文献表明，这些性别二态性的潜在机制来自：（1）基因在性染色体上的基因差异表达，以及（2）在关键的发育范围内，性激素对大脑的广泛影响。尽管这些影响对大脑发育和功能的独立和互动效应被认为对认知和行为的性二态模式有显着贡献，但该领域的研究受到限制。进一步的研究对于增加我们对性别染色体基因表达和性激素暴露的理解至关重要。性别染色体非整倍性（例如Turner综合征（'TS'，45，X）和Klinefelter综合征（“ KS'，47，XXY））代表了阐明性染色体基因表达和性激素对神经发育和功能的影响的独特范式。每种疾病的特征是异常数量的X染色体和受影响（基因型非摩萨克）个体通常显示出性激素的产生水平大大降低。由于TS和KS与神经解剖学和认知行为差异的特定谱有关，因此对这些疾病的研究可能会提供有关典型发育中发生性二态性脑差异的独特信息（男性具有46，XY基因型和女性，并且女性具有46，XX Genotype）。尽管以前已经独立研究了TS和KS，但迄今为止，没有对这些队列的直接比较，并且没有研究这些群体或将这些群体单独进行比较，或者与通常发展的男性和女性同类群体进行了比较。在这里，我们描述了一项首先研究的研究，旨在直接检查青春期前，年龄匹配的TS，具有KS的男孩以及通常发展的男性和女性对照的女孩之间的神经解剖学和认知行为功能的差异。拟议的项目建立在我们小组先前研究的引人注目的观察结果以及其他研究中，表明TS和KS中神经解剖学变异的空间模式可能在很大程度上是相对于典型发展的互补性。我们提出的横截面研究将是第一个直接比较同一研究中TS和KS的研究，目的是阐明不同性别染色体基因表达和相关性激素暴露对神经解剖学的早期（青春期前）作用。这项研究具有巨大的希望，可以提高我们对性别染色体基因表达和性激素对幼儿神经发育的影响，并相应地提供对与精神疾病风险和韧性有关的性别差异的神经过程的新见解。