Sleep patterns predicting stress resilience are dependent on sex

Sleep disturbances and stress have a well-established link with neuropsychiatric illness; however, the nature of this relationship remains unclear. Recently, studies using the mouse social-defeat stress model revealed a causal role for non-rapid eye movement (NREM) sleep in the maladaptive behavioral responses to stress. These results suggest a novel function for NREM sleep; as a response by cortical neurons to mitigate the maladaptive effects of stress. A major limitation in many social defeat studies has been the exclusion of females. Women exhibit a greater prevalence of both affective disorders and sleep disturbances compared to men, thus there is a clear need to understand sleep – stress interactions in females. The present study adapts recently developed female social-defeat stress models to allow social-defeat and EEG in male – female pairs. Our findings duplicated the behavioral responses that occurred in other female, nondiscriminatory, and male models of social-defeat stress. Analysis of electroencephalographic (EEG) recordings, before exposure to stress, revealed that susceptibility to the behavioral effects of stress was associated with increased post-defeat NREM sleep—exclusively in females. In males, increased NREM sleep after social defeat stress occurred only in resilient mice. A potential cause of these sleep differences was also identified prior to stress exposure; we identified sex differences in recovery from NREM-sleep loss, thus, suggesting a sex-difference in the homeostatic process regulating sleep. These contrasting responses reveal sexual dimorphism in both NREM sleep predicting resilience and NREM sleep changes induced by social-defeat stress. When considered in the context of existing human literature, these findings suggest that sex is a major factor influencing the interaction of sleep with maladaptive behavioral responses to stress.