Project IIStress 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 experiencesresult in region-specific alterations in BDNF levels. The overarching goal of this project is to test thehypothesis that the Val66Met polymorphism in the BDNF gene will moderate the effects of early life stress, inthe form of institutional/orphanage rearing, on the structure and function of the hippocampus, amygdala, andventromedial prefrontal cortex (including orbital prefrontal cortex). Participants will be 12-14 year old childrenadopted internationally between the ages of 1 month and 5 years after having lived for 75% or more of theirpre-adoption lives in institutions (hospitals, orphanage). We will test the hypothesis that BDNF Val66Metpolymorphism will moderate the impact of early life stress (dose/duration of institutional care) on structureand function of these regions (Center Aim 2). We will also examine whether these effects will be diminishedwith time in the adoptive home (Center Aim 3). This component of Project II will parallel manipulations ofenvironmental gain of function in the mouse model in Project III (Center Aim 3), while the environmentalstressor of early institutionalization will parallel early postnatal stress in the mouse (Center Aim 2). Project IIwill draw on the Administrative and Data Management Core as well as the Statistical Genetics Core of theCenter for support in processing and analysis of behavioral, imaging, and genetics data.
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