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。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 已有研究表明，压力会改变涉及学习(尤其是情境学习、线索学习和消亡学习)和认知控制的神经系统的发展。在人类和小鼠身上出现的新证据表明，应激经历会导致脑源性神经营养因子水平的区域特异性变化。该项目的主要目标是验证这样一种假设，即BDNF基因的Val66Met多态将缓和早期生活应激(以机构/孤儿院饲养的形式)对海马体、杏仁核和腹内侧额前皮质(包括眼眶前额皮质)的结构和功能的影响。参与者将是12至14岁的国际领养儿童，年龄在4个月至5岁之间，他们在机构(医院、孤儿院)生活了75%或更长时间后被收养。我们将检验这一假设，即BDNF Val66Met多态将缓和早期生活应激(机构护理的剂量/持续时间)对这些区域结构和功能的影响。我们还将研究这些影响在收养家庭中是否会随着时间的推移而减弱。这个项目是NIMH中心赠款的一部分，该中心还包括其他项目，研究BDNF基因对8-18岁典型发育阶段学习和认知控制的影响(纽约萨克勒研究所)，以及小鼠Val66Met多态的敲入基因模型，包括小鼠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.