Sleep patterns predicting stress resilience are dependent on sex

Neuropsychopharmacology. 2025 May 17. doi: 10.1038/s41386-025-02124-0. Online ahead of print.

ABSTRACT

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 duplicate the behavioral responses that occur in other female, nondiscriminatory, and male models of social-defeat stress. Analysis of electroencephalographic (EEG) recordings, before exposure to stress, reveal that resilience is associated with differences in both NREM and REM sleep that are dependent on sex. After social defeat stress, NREM sleep was increased only in resilient males. In females, susceptibility to stress was associated with increased durations in NREM-sleep bouts. A potential cause of these sleep differences was also identified prior to stress exposure, sex differences in recovery from NREM-sleep loss; thus, suggesting an underlying sex-difference in the homeostatic process regulating sleep interactions with social-defeat stress. These findings suggest that NREM sleep quality is lower in resilient females, whereas the amount of REM sleep is decreased in susceptible females-when compared to males of the same behavioral phenotype. Overall, our findings reveal sexual dimorphism in both the sleep characteristics predicting resilience and sleep changes induced by social-defeat stress.

PMID:40382501 | DOI:10.1038/s41386-025-02124-0