IMPACT OF BDNF GENOTYPE AND EARLY LIFE STRESS ON LEARNING AND BRAIN DEVELOPMENT

这个子项目是利用资源的许多研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 子项目的主要研究者可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 表示子项目使用的中心基础设施的估计数量， NCRR赠款不直接向子项目或子项目工作人员提供资金。 压力已被证明会改变参与学习（特别是上下文，线索和灭绝学习）和认知控制的神经系统的发展。在人类和小鼠中出现的证据表明，压力经历导致BDNF水平的区域特异性改变。该项目的首要目标是测试BDNF基因中的Val 66 Met多态性将缓和早期生活压力（以机构/孤儿院养育的形式）对海马体，杏仁核和腹内侧前额叶皮层（包括眶前额叶皮层）的结构和功能的影响的假设。参与者将是12-14岁的国际收养儿童，年龄在4个月至5岁之间，在收养前的75%或以上生活在机构（医院，孤儿院）。我们将测试的假设，BDNF Val 66 Met多态性将缓和的影响，早期生活压力（剂量/机构护理的持续时间）对这些地区的结构和功能。我们还将研究这些影响是否会随着在收养家庭的时间而减弱。该项目是NIMH中心赠款的一部分，该赠款包括解决BDNF基因型对8-18岁典型发育中学习和认知控制的影响的其他项目（Sackler Institute，纽约）和小鼠Val 66 Met多态性的敲入基因模型，包括出生后早期应激和小鼠学习的行为测量。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Stress has been shown to alter the development of neural systems involved in learning (particularly contextual, cued, and extinction learning) and cognitive control. Emerging evidence in the human and mouse suggests that stressful experiences result in region-specific alterations in BDNF levels. The overarching goal of this project is to test the hypothesis that the Val66Met polymorphism in the BDNF gene will moderate the effects of early life stress (in the form of institutional/orphanage rearing) on the structure and function of the hippocampus, amygdala and ventromedial prefrontal cortex (including orbital prefrontal cortex). Participants will be 12-14 year old children adopted internationally between the ages of 4 months and 5 years after having lived for 75% or more of their pre-adoption lives in institutions (hospitals, orphanage). We will test the hypothesis that the BDNF Val66Met polymorphism will moderate the impact of early life stress (dose/duration of institutional care) on structure and function of these regions. We will also examine whether these effects are diminished with time in the adoptive home. This project is part of an NIMH Center grant that includes additional projects addressing the impact of BDNF genotype on learning and cognitive control in typical development from 8-18 years of age (Sackler Institute, New York) and a knock-in gene model of the Val66Met polymorphism in the mouse, including early postnatal stress and behavioral measures of mouse learning.