Roughly 1.5 million children are abused or neglected each year in this country and this alarming trend has been documented now for over 30 years. In the absence of effective interventions, maltreated children often go on to develop a host of behavioral, emotional, cognitive, and medical sequelae that can be chronic and in many cases refractory to treatment. The total economic burden associated with early life stress (ELS) is estimated at $247 billion annually, placing it on equal footing with the costs for all cancers combined. ELS causes similar behavioral abnormalities in many mammalian species, including nonhuman primates and rodents, suggesting that animal models may help elucidate the molecular and cellular changes that guide these developmental changes in children. We have developed several models of ELS in mice and are investigating the role that microglia play in mediating the effects of ELS on neurodevelopment and behavior in these animal models. This is an innovative neuroimmunological approach that stems from a recent discovery that microglia, which are macrophages-like cells that populate the brain early in life, play a critical role in many aspects of normal neurodevelopment and are also highly sensitive to stress.
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- Jackowski A, Perera TD, Abdallah CG, Garrido G, Tang CY, Martinez J, Mathew SJ, Gorman JM, Rosenblum LA, Smith EL, Dwork AJ, Shungu DC, Kaffman A, Gelernter J, Coplan JD, Kaufman J. Early-life stress, corpus callosum development, hippocampal volumetrics, and anxious behavior in male nonhuman primates. Psychiatry Research: Neuroimaging. (2011) Apr 30;192(1):37-44. Epub 2011 Mar 5. NIHMS254578
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- Kaffman A, Krystal J.H. (2012). New Frontiers in Animal Research of Psychiatric Illness. Methods Mol Biol.829:3-30. PMC3337084.
- Wei, L., Hao, J., Kaffman, A. (2014). Early life stress inhibits expression of ribosomal RNA in the developing hippocampus. PLoS ONE, 9, e115283. PMC4269428
- Wei, L., Hao, J., Lacher, R.K., Abbott, T., Chung, L., Colangelo, C.M., and Kaffman, A. (2015). Early life stress perturbs key cellular programs in the developing mouse hippocampus. Developmental neuroscience. PMC4644446
- Delpech, J.C., Wei, L., Hao, J., Yu, X., Madore, C., Butovsky, O., and Kaffman, A. (2016). Early life stress perturbs the maturation of microglia in the developing hippocampus. Brain, behavior, and immunity. PMC5010940
- Dwyer, J.B., Kaffman, A. (2017). Epigenetics in Psychiatry: The Promise for New Biomarkers and Treatments. Kaplan & Sadock’s Comprehensive Textbook of Psychiatry, Tenth Edition, edited by Benjamin J. Sadock, Virginia A. Sadock, and Pedro Ruiz.