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Biard K, Douglass AB, Robillard R, et al. A pilot study of serotonin-1A receptor genotypes and rapid eye movement sleep sensitivity to serotonergic/cholinergic imbalance in humans: a pharmacological model of depression. Nat Sci Sleep. 2015;8:1-8doi: 10.2147/NSS.S94549.
Biard, K., Douglass, A. B., Robillard, R., & De Koninck, J. (2016). A pilot study of serotonin-1A receptor genotypes and rapid eye movement sleep sensitivity to serotonergic/cholinergic imbalance in humans: a pharmacological model of depression. Nature and science of sleep, 81-8. https://doi.org/10.2147/NSS.S94549
Biard, Kathleen, et al. "A pilot study of serotonin-1A receptor genotypes and rapid eye movement sleep sensitivity to serotonergic/cholinergic imbalance in humans: a pharmacological model of depression." Nature and science of sleep vol. 8 (2016): 1-8. doi: https://doi.org/10.2147/NSS.S94549
Biard K, Douglass AB, Robillard R, De Koninck J. A pilot study of serotonin-1A receptor genotypes and rapid eye movement sleep sensitivity to serotonergic/cholinergic imbalance in humans: a pharmacological model of depression. Nat Sci Sleep. 2015 Dec 18;8:1-8. doi: 10.2147/NSS.S94549. eCollection 2016. PMID: 26719734; PMCID: PMC4690650.
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Nat Sci Sleep. 2015 Dec 18;8:1-8. doi: 10.2147/NSS.S94549. eCollection 2016.

A pilot study of serotonin-1A receptor genotypes and rapid eye movement sleep sensitivity to serotonergic/cholinergic imbalance in humans: a pharmacological model of depression.

Nature and science of sleep

Kathleen Biard, Alan B Douglass, Rébecca Robillard, Joseph De Koninck

Affiliations

  1. School of Psychology, University of Ottawa, Ottawa, ON, Canada ; University of Ottawa Institute for Mental Health Research, University of Ottawa Institute for Mental Health Research, Ottawa, ON, Canada.
  2. University of Ottawa Institute for Mental Health Research, University of Ottawa Institute for Mental Health Research, Ottawa, ON, Canada ; Royal Ottawa Mental Health Center, University of Ottawa Institute for Mental Health Research, Ottawa, ON, Canada.
  3. University of Ottawa Institute for Mental Health Research, University of Ottawa Institute for Mental Health Research, Ottawa, ON, Canada.

PMID: 26719734 PMCID: PMC4690650 DOI: 10.2147/NSS.S94549

Abstract

RATIONALE: The serotonergic and cholinergic systems are jointly involved in regulating sleep but this system is theorized to be disturbed in depressed individuals. We previously reported that cholinergic and serotonergic agents induce sleep changes partially consistent with monoamine models of sleep disturbances in depression. One potential cause of disturbed neurotransmission is genetic predisposition. The G(-1019) allele of the serotonin-1A (5-HT1A) receptor promoter region predicts an increased risk for depression compared to the wild-type C(-1019) allele.

OBJECTIVE: The goal of this study was to investigate how serotonin-1A receptor genotypes mediate sleep sensitivity to pharmacological probes modeling the serotonergic/cholinergic imbalance of depression.

METHODS: Seventeen healthy female participants homozygous for either C (n=11) or G (n=6) alleles aged 18-27 years were tested on four nonconsecutive nights. Participants were given galantamine (an anti-acetylcholinesterase), buspirone (a serotonergic agonist), both drugs together, or placebos before sleeping.

RESULTS: As reported previously, buspirone significantly increased rapid eye movement (REM) latency (P<0.001), as well as awakenings, percentage of time spent awake, and percentage of time asleep spent in stage N1 (P<0.019). Galantamine increased awakenings, percentage of time spent awake, percentage of time asleep spent in stage N1, and percentage of time asleep spent in REM, and decreased REM latency and percentage of time asleep spent in stage N3 (P<0.019). Galantamine plus buspirone given together disrupted sleep more than either drug alone, lowering sleep efficiency and percentage of time asleep spent in stage N3 and increasing awakenings, percentage of time spent awake, and percentage of time asleep spent in stage N1 (P<0.019). There was no main effect of genotype nor was there a significant multivariate interaction between genotype and drug condition.

CONCLUSION: These findings are partially consistent with the literature about sleep in depression, notably short REM latency, higher percentage of total sleep time spent in REM, lower percentage of time asleep spent in stage N3, and increased sleep fragmentation. The C/G mutation in the serotonin-1A receptor promoter region does not appear to cause noticeable differences in the sleep patterns of a relatively small sample of healthy young females. Future studies with larger sample sizes are required.

Keywords: acetylcholine; buspirone; depression; galantamine; serotonin; sleep

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