Child abuse is associated with depression, although the emergence of depression is often delayed until adolescence or young adulthood. We propose to study an experimental model of active parental abuse that is associated with adolescent and adult manifestation of increased immobility time in a forced swim test model of depression. Specifically, infant rats receive an electric shock while interacting with their mother during a developmentally limited sensitive period that lasts until postnatal day 9. Our group found that compared to control rats (interacting with the mother without shock or shock without the mother);abusive attachment rats had significantly decreased amygdala size, disrupted social interactions with the mother, and enhanced amygdala 2-deoxy-glucose activity in infancy. However, methodological barriers have impeded the needed translation from this well documented and powerful model to our understanding of the neurobiology of abused and mood disordered children and adolescents. In this multidisciplinary application, we propose to bridge these domains by applying a novel fMRI technique that has been remarkably fruitful in revealing the developmental trajectories of human brain to developing rats. Specifically, we will map brain functional connectivity between prefrontal cortex and amygdala in weanling, adolescent, and young adult rats in which early life experiences have been experimentally manipulated. In the second phase of this R21/R33 application, we propose to extend our paradigm to pre-weanling rats. Attainment of our aims will dramatically accelerate the iterative development of the neuroscience of adverse early environments and their consequences on brain development.

Public Health Relevance

Development of Cortical-Amygdala Interactions Project Narrative Child abuse is often associated with depression in adolescence or young adulthood. We propose to study an experimental model of parental abuse that is associated with giving up more rapidly in a forced swim test model of depression. Our multidisciplinary team of investigators proposes to apply a new brain imaging technique that is helping us to learn about brain development in children, by now using it to understand brain development in young lab rats. Being able to use the same techniques in children and lab animals will improve our ability to understand how brain development is affected by adverse early life experiences.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Exploratory/Developmental Grants Phase II (R33)
Project #
4R33MH086952-04
Application #
8339476
Study Section
Special Emphasis Panel (ZMH1-ERB-L (04))
Program Officer
Garriock, Holly A
Project Start
2009-08-01
Project End
2014-04-30
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
4
Fiscal Year
2012
Total Cost
$421,759
Indirect Cost
$139,232
Name
Nathan Kline Institute for Psychiatric Research
Department
Type
DUNS #
167204762
City
Orangeburg
State
NY
Country
United States
Zip Code
10962
Yang, Zhen; Craddock, R Cameron; Margulies, Daniel S et al. (2014) Common intrinsic connectivity states among posteromedial cortex subdivisions: Insights from analysis of temporal dynamics. Neuroimage 93 Pt 1:124-37