Circadian Regulation of Depression: A Role for Serotonin

Overview

Journal Front Neuroendocrinol

Specialty Endocrinology

Date 2019 Apr 20

PMID 31002895

Citations 64

Authors

Rachel A Daut

Laura K Fonken

Affiliations

Soon will be listed here.

Abstract

Synchronizing circadian (24 h) rhythms in physiology and behavior with the environmental light-dark cycle is critical for maintaining optimal health. Dysregulation of the circadian system increases susceptibility to numerous pathological conditions including major depressive disorder. Stress is a common etiological factor in the development of depression and the circadian system is highly interconnected to stress-sensitive neurotransmitter systems such as the serotonin (5-hydroxytryptamine, 5-HT) system. Thus, here we propose that stress-induced perturbation of the 5-HT system disrupts circadian processes and increases susceptibility to depression. In this review, we first provide an overview of the basic components of the circadian system. Next, we discuss evidence that circadian dysfunction is associated with changes in mood in humans and rodent models. Finally, we provide evidence that 5-HT is a critical factor linking dysregulation of the circadian system and mood. Determining how these two systems interact may provide novel therapeutic targets for depression.

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References

Yamazaki S, Numano R, Abe M, Hida A, Takahashi R, Ueda M . Resetting central and peripheral circadian oscillators in transgenic rats. Science. 2000; 288(5466):682-5. DOI: 10.1126/science.288.5466.682. View

Peichl L . Diversity of mammalian photoreceptor properties: adaptations to habitat and lifestyle?. Anat Rec A Discov Mol Cell Evol Biol. 2005; 287(1):1001-12. DOI: 10.1002/ar.a.20262. View

Wirz-Justice A . Diurnal variation of depressive symptoms. Dialogues Clin Neurosci. 2008; 10(3):337-43. PMC: 3181887. View

Samson W, Said S, McCANN S . Radioimmunologic localization of vasoactive intestinal polypeptide in hypothalamic and extrahypothalamic sites in the rat brain. Neurosci Lett. 1979; 12(2-3):265-9. DOI: 10.1016/0304-3940(79)96073-7. View

Cascade E, Kalali A, Thase M . Use of antidepressants: expansion beyond depression and anxiety. Psychiatry (Edgmont). 2010; 4(12):25-8. PMC: 2861511. View

Gooley J, Lu J, Chou T, Scammell T, Saper C . Melanopsin in cells of origin of the retinohypothalamic tract. Nat Neurosci. 2001; 4(12):1165. DOI: 10.1038/nn768. View

Morin L, Blanchard J . Serotonergic modulation of the hamster wheelrunning rhythm: response to lighting conditions and food deprivation. Brain Res. 1991; 566(1-2):186-92. DOI: 10.1016/0006-8993(91)91697-y. View

Stephan F, Zucker I . Circadian rhythms in drinking behavior and locomotor activity of rats are eliminated by hypothalamic lesions. Proc Natl Acad Sci U S A. 1972; 69(6):1583-6. PMC: 426753. DOI: 10.1073/pnas.69.6.1583. View

Donner N, Kubala K, Hassell Jr J, Lieb M, Nguyen K, Heinze J . Two models of inescapable stress increase mRNA expression in the anxiety-related dorsomedial part of the dorsal raphe nucleus. Neurobiol Stress. 2018; 8:68-81. PMC: 5842308. DOI: 10.1016/j.ynstr.2018.01.003. View

10.

Dudley T, DiNardo L, Glass J . In vivo assessment of the midbrain raphe nuclear regulation of serotonin release in the hamster suprachiasmatic nucleus. J Neurophysiol. 1999; 81(4):1469-77. DOI: 10.1152/jn.1999.81.4.1469. View

11.

Vandewalle G, Gais S, Schabus M, Balteau E, Carrier J, Darsaud A . Wavelength-dependent modulation of brain responses to a working memory task by daytime light exposure. Cereb Cortex. 2007; 17(12):2788-95. DOI: 10.1093/cercor/bhm007. View

12.

Comas M, Beersma D, Hut R, Daan S . Circadian phase resetting in response to light-dark and dark-light transitions. J Biol Rhythms. 2008; 23(5):425-34. DOI: 10.1177/0748730408321567. View

13.

LeGates T, Altimus C, Wang H, Lee H, Yang S, Zhao H . Aberrant light directly impairs mood and learning through melanopsin-expressing neurons. Nature. 2012; 491(7425):594-8. PMC: 3549331. DOI: 10.1038/nature11673. View

14.

Hattar S, Kumar M, Park A, Tong P, Tung J, Yau K . Central projections of melanopsin-expressing retinal ganglion cells in the mouse. J Comp Neurol. 2006; 497(3):326-49. PMC: 2885916. DOI: 10.1002/cne.20970. View

15.

van der Horst G, Muijtjens M, Kobayashi K, Takano R, Kanno S, Takao M . Mammalian Cry1 and Cry2 are essential for maintenance of circadian rhythms. Nature. 1999; 398(6728):627-30. DOI: 10.1038/19323. View

16.

Azmitia E, Segal M . An autoradiographic analysis of the differential ascending projections of the dorsal and median raphe nuclei in the rat. J Comp Neurol. 1978; 179(3):641-67. DOI: 10.1002/cne.901790311. View

17.

Fonken L, Aubrecht T, Melendez-Fernandez O, Weil Z, Nelson R . Dim light at night disrupts molecular circadian rhythms and increases body weight. J Biol Rhythms. 2013; 28(4):262-71. PMC: 4033305. DOI: 10.1177/0748730413493862. View

18.

Bohacek J, Manuella F, Roszkowski M, Mansuy I . Hippocampal gene expression induced by cold swim stress depends on sex and handling. Psychoneuroendocrinology. 2014; 52:1-12. DOI: 10.1016/j.psyneuen.2014.10.026. View

19.

Amir S, Lamont E, Robinson B, Stewart J . A circadian rhythm in the expression of PERIOD2 protein reveals a novel SCN-controlled oscillator in the oval nucleus of the bed nucleus of the stria terminalis. J Neurosci. 2004; 24(4):781-90. PMC: 6729822. DOI: 10.1523/JNEUROSCI.4488-03.2004. View

20.

Lesch K, Waider J . Serotonin in the modulation of neural plasticity and networks: implications for neurodevelopmental disorders. Neuron. 2012; 76(1):175-91. DOI: 10.1016/j.neuron.2012.09.013. View