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

描述（由申请人提供）：本K01申请的目的是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，并加强神经影像学（特别是弥散张量成像）和遗传学方面的训练。培训计划包括课程作业、辅导课和2个重点研究项目，这些项目将使候选人成为一名成功的独立研究者，研究调节男女神经发育障碍差异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差别很大。早发性疾病，如自闭症，更常发生在男性身上；其他疾病，如精神分裂症，在男性和女性中发病率相似，但性别在表达上有所不同。据推测，这些疾病的患病率和表达与大脑发育的性别差异有关。X染色体的影响和早期暴露于性腺激素是一个强有力的候选因果作用。这项研究的目的是：(1)描述从出生到2岁大脑发育的性别差异；(2)检测患有特纳综合征（Turner syndrome）婴儿的大脑发育是否发生改变。特纳综合征是一种明确的遗传疾病，由一条性染色体部分或完全丧失引起。为了解决目标1，将使用高分辨率MRI，包括弥散张量成像（DTI），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。为了实现目标2，将使用高分辨率MRI（包括DTI）来比较30名特纳综合征（X染色体单体）婴儿与30名匹配对照组的大脑发育。公共卫生相关性：生命的最初几年是产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疾病的发展至关重要。目前，我们对这一时期的两性异形现象知之甚少。更好地了解早期神经生物学性别差异及其发展机制对于理解不同性别对神经发育障碍的不同易感性和表达至关重要。最终，这将对早期诊断和治疗产生重要影响。此外，这项研究将为特纳综合征何时出现大脑异常提供新的信息，并有助于阐明激素治疗在产生和/或改善大脑异常发育中的潜在作用。

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.