Project 2: BDNF Genotype and Early Like Stress on Learning in Adolescence

项目二 压力已被证明会改变参与学习的神经系统的发育（上下文，线索， 灭绝）。此外，在人类和老鼠身上出现的证据表明， 导致BDNF水平的区域特异性改变。这个项目的首要目标是测试 假设BDNF基因中的Val 66 Met多态性将减轻早期生活压力的影响， 机构/孤儿院养育的形式，海马体、杏仁核的结构和功能， 腹内侧前额叶皮质（包括眶前额叶皮质）。参加者将是12-14岁的儿童 在国际上，1个月至5岁的儿童在生活了75%或更多的时间后， 收养前生活在机构（医院、孤儿院）。我们将检验BDNF Val 66 Met 多态性将缓和早期生活压力（机构护理的剂量/持续时间）对结构的影响 和这些区域的功能（中心目标2）。我们还将研究这些影响是否会减弱 在收养家庭的时间（中心目标3）。项目二的这一部分将与 在项目III（中心目标3）中，小鼠模型的功能环境增益，而环境增益 早期机构化的应激源将与小鼠中的早期出生后应激平行（中心目标2）。项目二 将利用行政和数据管理核心以及统计遗传学核心， 行为、成像和遗传学数据处理和分析支持中心。

Project II Stress has been shown to alter the development of neural systems involved in learning (contextual, cued, and extinction). Moreover, 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 1 month 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 BDNF Val66Met polymorphism will moderate the impact of early life stress (dose/duration of institutional care) on structure and function of these regions (Center Aim 2). We will also examine whether these effects will be diminished with time in the adoptive home (Center Aim 3). This component of Project II will parallel manipulations of environmental gain of function in the mouse model in Project III (Center Aim 3), while the environmental stressor of early institutionalization will parallel early postnatal stress in the mouse (Center Aim 2). Project II will draw on the Administrative and Data Management Core as well as the Statistical Genetics Core of the Center for support in processing and analysis of behavioral, imaging, and genetics data.