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.

National Institute of Health (NIH)
National Institute of Mental Health (NIMH)
Exploratory/Developmental Grants Phase II (R33)
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Special Emphasis Panel (ZMH1-ERB-L (04))
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Garriock, Holly A
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Nathan Kline Institute for Psychiatric Research
United States
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Yan, C-G; Rincón-Cortés, M; Raineki, C et al. (2017) Aberrant development of intrinsic brain activity in a rat model of caregiver maltreatment of offspring. Transl Psychiatry 7:e1005
Chen, Huaihou; Kelly, Clare; Castellanos, F Xavier et al. (2015) Quantile rank maps: a new tool for understanding individual brain development. Neuroimage 111:454-63
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