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

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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.