Hall, A. G.; Burek, D. J.; Hisey, E. E.; Seabrook, L. T.; Fritsch, E. L.; Beatty, Z. G.; Ressler, K. J.; Kangas, B. D.; Carlezon, W. A.

Early-life stress (ELS) can produce long-lasting effects that increase the risk for mood and anxiety disorders. Transdiagnostic symptoms include anhedonia (reduced reward sensitivity) and sleep disruption, both of which are quantifiable via objective endpoints that can be utilized across species. Here we used a mouse model for ELS - exposure to juvenile chronic social defeat stress (jCSDS) - together with translationally-applicable endpoints to examine correspondence between sleep patterns and anhedonia. These initial studies focused on males, which typically show robust defeat-induced anhedonia phenotypes. Exposure to jCSDS produced reductions in open-field social behavior, an endpoint commonly used in mice to quantify stress effects, during adulthood. Mice were then implanted with wireless transmitters that enable continuous EEG-derived analysis of sleep architecture. Following assessment of baseline sleep patterns, mice were tested in a rodent version of the Probabilistic Reward Task (PRT), a procedure used to quantify reward responsiveness in humans, during the light phase of their diurnal cycle. These studies revealed significant associations between baseline sleep architecture and anhedonic phenotypes in jCSDS-exposed mice: higher anhedonia correlated with less time awake and more time in slow wave sleep (SWS) during the light phase, and more time awake and less time in rapid eye movement (REM) sleep and SWS during the dark (active) phase. Our findings suggest that sleep patterns represent a biomarker that can predict stress-susceptible (higher anhedonia) and resilient (lower anhedonia) phenotypes. This work enhances our understanding of relationships between sleep and anhedonia, and may provide a basis for precision approaches to treat ELS-induced pathophysiology.