Influence of Schizophrenia-Associated Gene Egr3 on Sleep Behavior and Circadian Rhythms in Mice
Open accessAbstract
Up to 80% of people meeting DSM-IV definitions for schizophrenia will exhibit difficulties with sleep, along with a breakdown in circadian entrainment and rhythmicity. The changes to the sleep and circadian systems in this population are thought to be interdependent, as evidenced by the frequent use of the combined term “sleep and circadian rhythm disruption” or “SCRD” to describe their occurrence. To understand links between sleep and circadian problems in the schizophrenia population, we analyzed the duration and rhythmicity of sleep behavior in mice lacking function of the immediate early gene early growth response 3 ( Egr3). EGR3 has been associated with schizophrenia risk in humans, and Egr3-deficient (-/-) mice display various features of schizophrenia that are responsive to antipsychotic treatment. While Egr3-/- mice slept less than their wildtype (WT) littermates, they showed no evidence of circadian disorganization; in fact, circadian rhythms of activity were more robust in these mice compared with WT, as measured by time series analysis and the relative amplitude index of Van Someren’s suite of non-parametric circadian rhythm analyses. Differences in circadian robustness were maintained when the animals were transferred to several weeks of housing under constant darkness or constant light. Together, our results suggest that Egr3-/- mice retain control over the circadian timekeeping of sleep and wake, while showing impaired sleep. The findings are compatible with those from a surprising array of mouse models of schizophrenia and raise the possibility that SCRD may be 2 separate disorders in the schizophrenia population requiring different treatment strategies.
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Egr3-deficient mice display behaviors that are reminiscent of schizophrenia and sleep less than wild-type controls, even though the circadian organization of the sleep-wake cycle remained intact.
“Additional support for this candidate gene is provided by Egr3-deficient mice (−/−), which display behaviors that are reminiscent of SZ and sleep less than WT controls, even though the circadian organization of the sleep-wake cycle remained intact169.”
From Circadian rhythm disruption and mental health (2020) · cites this paper as [169]
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Circadian rhythm disruption and mental health
Walker, W. H., Walton, J. C., DeVries, A. C., & Nelson, R. J. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-0694-0 · Cited by 1,030 · see citing works
- Authors
- Maple, A. M., Rowe, R. K., Lifshitz, J., Fernandez, F., & Gallitano, A. L.
- Affiliations
- University of Arizona College of Medicine- Phoenix (US)
- Barrow Neurological Institute (US)
- University of Arizona (US)
- Corresponding author
- Gallitano, Amelia L.
- Venue
- Journal of Biological Rhythms
- Publisher
- SAGE Publications
- Published
- 2018-10-15
- Volume
- 33
- Issue
- 6
- Pages
- 662-670
- ISSN
- 0748-7304 (ISSN-L)
- 1552-4531
- PMC
- PMC8651219
- OpenAlex
- W2895878990
- Cited by
- 17
- References
- 52
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 5 · 2023: 1 · 2022: 1 · 2021: 2 · 2020: 6
- FWCI
- 1.13
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Biological Rhythms (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Arizona Department of Health Services
- National Institute of Mental Health (R01 MH097803)
- Science Foundation Arizona (Bisgrove Scholar Award)
- UA BIO5 Institute
- American Sleep Medicine Foundation (Focused Project Award)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Keywords
- EGR3, schizophrenia, sleep behavior, circadian rhythm, constant darkness, constant light, circadian timekeeping, sleep duration
- MeSH terms
- Animals, Circadian Rhythm, Darkness, Female, Motor Activity, Schizophrenia, Sleep, Mice, Knockout, Mice, Early Growth Response Protein 3
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