Stanford Advisors


All Publications


  • Sleep patterns predicting stress resilience are dependent on sex. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology Bush, B. J., Mohamed, A., Andrews, E. J., Cain, G., Fawole, A., Johnson, H., Arocho, A., Qiao, Z., Paul, K. N., Ehlen, J. C. 2025

    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.

    View details for DOI 10.1038/s41386-025-02124-0

    View details for PubMedID 40382501

    View details for PubMedCentralID 5551063

  • Extended Amygdala Neural Circuits Linking Hormonal Influences on Body Temperature to Sleep and Circadian Rhythms Bush, B., Sardar, H., Aloboudi, F., Hoang, I., Rogers, E., Morningstar, A., Ma, Y., Cengio, L., Buchanan, R., Gibson, E., Giardino, W. OXFORD UNIV PRESS INC. 2025: A39
  • Non-rapid eye movement sleep determines resilience to social stress. eLife Bush, B. J., Donnay, C., Andrews, E. A., Lewis-Sanders, D., Gray, C. L., Qiao, Z., Brager, A. J., Johnson, H., Brewer, H. C., Sood, S., Saafir, T., Benveniste, M., Paul, K. N., Ehlen, J. C. 2022; 11

    Abstract

    Resilience, the ability to overcome stressful conditions, is found in most mammals and varies significantly among individuals. A lack of resilience can lead to the development of neuropsychiatric and sleep disorders, often within the same individual. Despite extensive research into the brain mechanisms causing maladaptive behavioral-responses to stress, it is not clear why some individuals exhibit resilience. To examine if sleep has a determinative role in maladaptive behavioral-response to social stress, we investigated individual variations in resilience using a social-defeat model for male mice. Our results reveal a direct, causal relationship between sleep amount and resilience-demonstrating that sleep increases after social-defeat stress only occur in resilient mice. Further, we found that within the prefrontal cortex, a regulator of maladaptive responses to stress, pre-existing differences in sleep regulation predict resilience. Overall, these results demonstrate that increased NREM sleep, mediated cortically, is an active response to social-defeat stress that plays a determinative role in promoting resilience. They also show that differences in resilience are strongly correlated with inter-individual variability in sleep regulation.

    View details for DOI 10.7554/eLife.80206

    View details for PubMedID 36149059

    View details for PubMedCentralID PMC9586557

  • Nitrergic neurons of the dorsal raphe nucleus encode information about stress duration. PloS one Nichols, I. S., Jones, M. I., Okere, C., Ananaba, G., Bush, B., Gray, C., Brager, A., Ehlen, J. C., Paul, K. 2017; 12 (11): e0187071

    Abstract

    Nitrergic neurons of the dorsal raphe nucleus (DRN) may play a role in physiological stress responses. The caudal lateral wings (CLW) are unique compared to other rostral-caudal DRN sub-regions because they contain distinct nitric oxide (NO) synthase (NOS) populations that are independent of tryptophan hydroxylase (TPH). NOS neurons in the CLW are also highly activated during acute restraint stress. However, the effects of acute stress duration on NOS activation in the CLW are unclear. Here NADPH-d, an index of NOS activity, is used to show that sub-regions of the DRN have differential NOS activation in response to 6 hours of restraint stress in rats. We report increased NOS activity through 6 hours of restraint in the caudal lateral wings and ventromedial sub-regions. These data suggest that, NOS neurons may play a dynamic role in the response to stress duration.

    View details for DOI 10.1371/journal.pone.0187071

    View details for PubMedID 29125838

    View details for PubMedCentralID PMC5681257