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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Specialized Center (P50)
Project #
5P50MH079513-02
Application #
7900724
Study Section
Special Emphasis Panel (ZMH1)
Project Start
2009-05-01
Project End
2013-04-30
Budget Start
2009-05-01
Budget End
2010-04-30
Support Year
2
Fiscal Year
2009
Total Cost
$379,949
Indirect Cost
Name
Weill Medical College of Cornell University
Department
Type
DUNS #
060217502
City
New York
State
NY
Country
United States
Zip Code
10065
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Dincheva, Iva; Yang, Jianmin; Li, Anfei et al. (2017) Effect of Early-Life Fluoxetine on Anxiety-Like Behaviors in BDNF Val66Met Mice. Am J Psychiatry 174:1203-1213
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Proenca, Catia C; Song, Minseok; Lee, Francis S (2016) Differential effects of BDNF and neurotrophin 4 (NT4) on endocytic sorting of TrkB receptors. J Neurochem 138:397-406

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