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Arie Kaffman, MD, PhD

Research Scientist in the Department of Psychiatry

Research Summary

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 currently have 3 inter-related projects in the lab:

Project 1- Connectivity and behavior

Using diffusion MRI we recently found that mice exposed to complex and unpredictable stress early in life, abbreviated as UPS show several neuroanatomical changes that resemble those seen in humans, findings that were seen in both male and female mice (White 2020, doi: 10.7554/eLife.58301). Interestingly, UPS increases fronto-limbic connectivity in male, but not female mice. The goals of this project is to understand how changes in connectivity modify complex behaviors such as anxiety, social exploration and impulsivity. Further, we are looking at how more predictable and less severe forms of stress early in life alter connectivity, fractional anisotropy and volumetric changes. This work is a collaboration with several labs including the DeLeon and Hyder labs at Yale and Dr. Zhang lab at NYU.

Project 2- Role of microglia

We have previously shown that early life stress (ELS) alters morphology, gene expression and phagocytic activity of microglia in the developing brain (Delpech 2016, doi: 10.1016/j.bbi.2016.06.006). This is important because microglia, which are the brain’s innate immune cells, play a critical role in many developmental processes that are altered by ELS including connectivity, myelination, synaptogenesis and neurogenesis (Johnson and Kaffman, doi: 10.1016/j.bbi.2017.06.008). The focus of this project is to understand how different stressors early in life alter microglial function during development and how these changes lead to structural and behavioral changes later in life.

Project 3- Effects of ELS on myelination

ELS has been shown to impair myelination in rodents, non-human primates and humans (Islam and Kaffman, doi:10.3389/fnins.2021.657693). This project explores the mechanisms by which ELS impairs myelin development and tests whether correcting these myelination deficits can restore normal connectivity and behavior later in life.

Coauthors

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Selected Publications