Project 3: A Multimodal Imaging Study of the Effects of Altered Serotonin

项目 3：改变血清素影响的多模态成像研究

基本信息

批准号：
8478208
负责人：
BRADLEY S PETERSON
金额：
$ 30.32万
依托单位：
NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
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：
2013-05-01 至 2015-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8478208
关键词：
Age Alleles Animals Behavior Behavioral Blood flow Brain Cerebrovascular Circulation Characteristics Child Data Depressed mood Development Electroencephalography Exposure to Fetus Fiber Genes Genetic Genetic Polymorphism Genetic Variation Genotype Goals Growth Factor Human Image Individual Differences Infant Investigation Lead Life Magnetic Resonance Imaging Measurement Measures Mediating Mediator of activation protein Mental Depression Modality Mothers Multimodal Imaging Mus N-acetylaspartate Neonatal Neurons Newborn Infant Nucleic Acid Regulatory Sequences Parietal Parietal Lobe Pattern Perfusion Pharmaceutical Preparations Phenotype Pregnancy Recording of previous events Regulation Selective Serotonin Reuptake Inhibitor Series Serotonin Signal Transduction Specificity Structure System Variant base brain volume cohort density design follow-up frontal lobe indexing maternal depression neural growth neurobehavioral prenatal exposure promoter serotonin transporter trait white matter

项目摘要

The central concept underlying all of the projects in this center is that during early development serotonin is a vitally important neural growth factor and regulator of brain maturation. Thus, environmental, genetic, and pathological factors that influence serotonin availability will profoundly influence brain structure, function and ultimately, behavior. Results from animal and human studies suggest that differences in serotonin function, either associated with polymorphisms in regulatory regions of the serotonin transporter gene or prenatal exposure to SSRIs, may underlie individual differences in fundamental neurobehavioral traits. No studies thus far have characterized early life phenotypes of polymorphisms in the serotonin system, and investigations of how pharmacologic perturbations of this system influence neurobehavioral traits in infants have been very limited. To date, no human studies have identified variation in the anatomical and functional characteristics of the newborn brain that are associated with altered serotonin signaling. In Project 3, we propose assessing the effects of both genetic variation and prenatal exposure to SSRIs on brain structure and function as a convergent strategy to identify the influences of altered serotonin signaling on early brain development. Because both SSRIs and the SS genotype of the serotonin transporter should promote increased levels of extracelluar serotonin, the overall hypothesis of this project is that the effects of prenatal exposure to SSRIs on brain development will be similar to those of the SS polymorphism. The primary goals of the project are to define the effects that prenatal exposure to SSRIs and genetic variation in regulation of the serotonin transporter have on brain structure, blood flow, neurometabolite concentrations, and neuroelectric functioning using MRI data and high-density (128 lead) EEG recordings acquired within the month of life. In Aim 1, these studies will focus on groups of infants with or without exposure to SSRIs during gestation. In Aim 2, a similar series of measurements will be made on groups of infants that vary with regard to polymorphisms in the serotonin transporter.

该中心所有项目的基础概念是在早期发育期间，羟色胺是至关重要的神经生长因素和脑成熟的调节剂。因此，影响5-羟色胺可用性的环境，遗传和病理因素将深刻影响大脑结构，功能和最终行为。动物和人类研究的结果表明，羟色胺功能的差异与5-羟色胺转运蛋白转运蛋白基因的多态性相关的差异或与SSRI的产前暴露有关，可能是基本神经行为特征的个体差异的基础。迄今为止，尚无研究中尚未表征5-羟色胺系统中多态性的早期生命表型，并研究了该系统的药理扰动如何影响婴儿的神经行为特征非常有限。迄今为止，尚无人类研究确定新生大脑的解剖学和功能特征的变化，这些特征与羟色胺信号改变有关。在项目3中，我们提出了评估遗传变异和产前暴露于SSRI对大脑结构和功能作为收敛策略的影响，以鉴定5-羟色胺信号转化对早期大脑发育的影响。因为SSRIS和5-羟色胺转运蛋白的SS基因型均应促进胞外5-羟色胺的水平增加，所以该项目的总体假设是，在SSRIS上暴露于SSRIS对脑发育的影响将与SS多态性相似。该项目的主要目标是确定在5-羟色胺转运蛋白调节中暴露于SSRI的影响以及使用MRI数据和高密度数据（128个Leec记录）EEG记录在生命月份内收购的羟色胺转运蛋白对大脑结构，血流，神经元代谢物浓度以及神经电性功能的影响。在AIM 1中，这些研究将集中在妊娠期间有或没有SSRI的婴儿组。在AIM 2中，将对与5-羟色胺转运蛋白中多态性不同的婴儿组进行类似的测量。