Sex Differences in Early Brain Development; Brain Development in Turner Syndrome

描述(由申请人提供)：这份K01申请的目标是通过强化神经成像(特别是扩散张量成像)和遗传学培训来补充候选人在发育神经内分泌学和心理学方面的广泛背景。培训计划包括课程作业、教程和两个重点研究项目，这些项目将使候选人能够成功地成为一名独立研究员，研究调节男女神经发育障碍的不同易感性和表达的发育机制。许多精神疾病的相对风险在男性和女性之间有很大差异。自闭症等早发性疾病在男性中更常见；其他疾病，如精神分裂症，在男性和女性中的发生率相似，但性别在表现上有所不同。有人假设，这些疾病的流行和表达与大脑发育的性别差异有关。X染色体效应和早期暴露于性腺激素是产生因果关系的重要因素。这项研究的目的是(1)表征从出生到2岁的大脑发育的性别差异；(2)测试特纳综合征婴儿的大脑发育是否发生改变，特纳综合征是一种明确定义的遗传疾病，由其中一条性染色体部分或完全丢失引起。为了解决目标1，包括扩散张量成像(DTI)在内的高分辨率磁共振将被用来在250名儿童的纵向队列中表征从出生到2岁的大脑发育的性别差异。为了解决目标2，将使用包括DTI在内的高分辨率MRI来比较30名患有特纳综合征(X单体)的婴儿和30名匹配的对照组婴儿的大脑发育。与公共卫生相关：生命的头几年是出生后大脑发育最活跃的阶段；这一时期的变化可能对自闭症和精神分裂症等精神障碍的发展至关重要。目前，人们对这一时期的性二型性知之甚少。更好地了解早期神经生物学性别差异及其发展机制，对于了解男女神经发育障碍的差异易感性和表达至关重要。最终，这将对早期诊断和治疗具有重要意义。此外，这项研究将提供特纳综合征中大脑异常何时出现的新信息，并有助于阐明激素疗法在创造和/或改善大脑发育异常方面的潜在作用。

DESCRIPTION (provided by applicant): The goal of this K01 application is to complement the candidate's extensive background in developmental neuroendocrinology and psychology with intensive training in neuroimaging (particularly diffusion tensor imaging) and training in genetics. The training plan includes coursework, tutorials, and 2 focused research projects that will allow the candidate to succeed as an independent investigator studying the developmental mechanisms which modulate differential vulnerability to and expression of neurodevelopment disorders in each sex. Relative risk for many psychiatric disorders differs dramatically in males and females. Early-onset disorders, such as autism, occur more often in males; other conditions, such as schizophrenia, occur at similar rates in males and females, but the sexes differ in expression. It has been hypothesized that the prevalence and expression of these disorders is related to sex differences in brain development. X- chromosome effects and early exposure to gonadal hormones are strong candidates for a causal role. The aims of the research are (1) to characterize sex differences in brain development from birth to age 2; (2) to test whether brain development is altered in infants with Turner syndrome, a well-defined genetic disorder resulting from the partial or complete loss of one of the sex chromosomes. To address aim 1, high resolution MRI, including diffusion tensor imaging (DTI), will be used to characterize sex differences in brain development from birth to age 2 in a longitudinal cohort of 250 children. To address aim 2, high resolution MRI, including DTI, will be used to compare brain development in 30 infants with Turner syndrome (X monosomy) to 30 matched controls. PUBLIC HEALTH RELEVANCE: the first few years of life are the most dynamic phase of postnatal brain growth; changes in this period may be critical in the development psychiatric disorders such as autism and schizophrenia. Currently, very little is known about sexual dimorphism in this period. A better knowledge of early neurobiological sex differences and the mechanisms through which they develop is critical to understand differential vulnerability to and expression of neurodevelopment disorders in each sex. Ultimately, this will have important implications for early diagnosis and treatment. In addition, this study will provide new information on when brain abnormalities arise in Turner Syndrome and help clarify the potential role of hormone therapies in creating and/or ameliorating abnormal brain development.