OVERALL CENTER ABSTRACT This application is in response to Program Announcement (PA) Number PAR-06-053 Interdisciplinary Developmental Centers for Mental Health (IDSC): Mature Centers (P50). The proposed Center represents a unique marshaling of the talents of a distinguished group of scientists with expertise in cognitive and affective development and systems-level neuroscience, pediatric imaging, molecular biology, mouse models, and biostatistical analysis. We will use an endophenotype approach to examine the impact of brain-derived neurotrophic factor (BDNF) and experiential events (e.g., stress and enrichment) across development on three forms of learning (contextual, cued, extinction) and their associated neural circuitry. Disruption of these learning systems is at the core of many forms of psychiatric disorders, allowing us to examine vulnerability and resistance to psychopathology as a function of stress and genotype. The strength of this proposal is the elegant mapping of human and animal projects, such that transgenic mouse models will provide a constrained interpretation of gene-environment interactions in developing humans. The Center is comprised of 3 highly interdependent projects and 2 cores (Administrative and Data Management Core and Statistical Genetics Cores) designed to provide resources and support for each of the projects. There are three overarching Center aims. First, using both human imaging and animal models, we will track the developmental trajectory of brain systems involved in learning as a function of BDNF genotype (Projects I and III). Second, we will characterize the impact of different forms of stress, including early, severe stress (Projects II and III) and current, mild stress (Project I) on these brain systems during development as a function of BDNF genotype. Third, we will test the extent to which the endophenotypic differences as a function of BDNF genotype can be rescued genetically or environmentally (Project I, II, and III). The proposed studies will collectively test three sets of hypotheses about the role of gene-environment interactions in learning and development in the context of BDNF. These hypotheses include predictions pertaining to: 1) changes in behavioral and neuroanatomical measures of learning as a function of both BDNF genotype and developmental changes in BDNF levels;2) how BDNF genotype modulates the impact adversity on learning and associated circuitry;and 3) rescue of BDNF phenotype through environmental and/or genetic manipulations.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Specialized Center (P50)
Project #
Application #
Study Section
Special Emphasis Panel (ZMH1-ERB-A (05))
Program Officer
Garvey, Marjorie A
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Weill Medical College of Cornell University
Schools of Medicine
New York
United States
Zip Code
Johnson, D C; Casey, B J (2015) Easy to remember, difficult to forget: the development of fear regulation. Dev Cogn Neurosci 11:42-55
Stellern, Sarah; Esposito, Elisa; Mliner, Shanna et al. (2014) Increased freezing and decreased positive affect in postinstitutionalized children. J Child Psychol Psychiatry 55:88-95
Dreyfuss, Michael; Caudle, Kristina; Drysdale, Andrew T et al. (2014) Teens impulsively react rather than retreat from threat. Dev Neurosci 36:220-7
Dincheva, Iva; Pattwell, Siobhan S; Tessarollo, Lino et al. (2014) BDNF modulates contextual fear learning during adolescence. Dev Neurosci 36:269-76
Pitula, Clio E; Thomas, Kathleen M; Armstrong, Jeffrey M et al. (2014) Peer victimization and internalizing symptoms among post-institutionalized, internationally adopted youth. J Abnorm Child Psychol 42:1069-76
Pattwell, Siobhan S; Lee, Francis S; Casey, B J (2013) Fear learning and memory across adolescent development: Hormones and Behavior Special Issue: Puberty and Adolescence. Horm Behav 64:380-9
Hartley, Catherine A; Casey, B J (2013) Risk for anxiety and implications for treatment: developmental, environmental, and genetic factors governing fear regulation. Ann N Y Acad Sci 1304:1-13
Malter Cohen, Matthew; Jing, Deqiang; Yang, Rui R et al. (2013) Early-life stress has persistent effects on amygdala function and development in mice and humans. Proc Natl Acad Sci U S A 110:18274-8
Pattwell, Siobhan S; Bath, Kevin G; Perez-Castro, Rosalia et al. (2012) The BDNF Val66Met polymorphism impairs synaptic transmission and plasticity in the infralimbic medial prefrontal cortex. J Neurosci 32:2410-21
Bath, Kevin G; Chuang, Jocelyn; Spencer-Segal, Joanna L et al. (2012) Variant brain-derived neurotrophic factor (Valine66Methionine) polymorphism contributes to developmental and estrous stage-specific expression of anxiety-like behavior in female mice. Biol Psychiatry 72:499-504

Showing the most recent 10 out of 36 publications