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

项目II 压力已经被证明改变了参与学习的神经系统的发展(上下文，线索， 和灭绝)。此外，在人类和老鼠身上出现的证据表明，紧张的经历 导致脑源性神经营养因子水平的区域特异性变化。该项目的总体目标是测试 假设BDNF基因中的Val66Met多态将缓解早期生活应激的影响，在 机构/孤儿院养育的形式，对海马体、杏仁核和 腹内侧前额叶皮质(包括眼眶前额叶皮质)。参与者为12-14岁的儿童 在生活了75%或更长时间后，在1个月至5岁之间被国际收养 收养前居住在机构(医院、孤儿院)。我们将检验BDNF Val66Met的假设 多态将缓和早期生活应激(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 在领养家庭的时间(中心目标3)。项目II的这一组成部分将并行操作 在项目III(中心目标3)中的小鼠模型中的功能环境增益，而环境 早期制度化的应激源将平行于小鼠出生后的早期应激(中心目标2)。项目II 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.