Circadian rhythms and mood regulation: Insights from pre-clinical models

doi:10.1016/j.euroneuro.2011.07.008

European Neuropsychopharmacology

Volume 21, Supplement 4, September 2011, Pages S683-S693

https://doi.org/10.1016/j.euroneuro.2011.07.008 Get rights and content

Abstract

Affective disorders such as major depression, bipolar disorder, and seasonal affective disorder are associated with major disruptions in circadian rhythms. Indeed, altered sleep/wake cycles are a critical feature for diagnosis in the DSM IV and several of the therapies used to treat these disorders have profound effects on rhythm length and stabilization in human populations. Furthermore, multiple human genetic studies have identified polymorphisms in specific circadian genes associated with these disorders. Thus, there appears to be a strong association between the circadian system and mood regulation, although the mechanisms that underlie this association are unclear. Recently, a number of studies in animal models have begun to shed light on the complex interactions between circadian genes and mood-related neurotransmitter systems, the effects of light manipulation on brain circuitry, the impact of chronic stress on rhythms, and the ways in which antidepressant and mood-stabilizing drugs alter the clock. This review will focus on the recent advances that have been gleaned from the use of pre-clinical models to further our understanding of how the circadian system regulates mood.

Section snippets

Introduction to circadian timing regulation

Nearly every organism on the planet has circadian rhythms of ~ 24 h in multiple biological processes which are controlled by both the light–dark cycle and an internal clock. The circadian system is composed of three main components: input pathways which relay environmental information to the clock, the central clock itself which can generate rhythms even in the absence of environmental input, and output pathways which synchronize clocks in individual cells and organs throughout the brain and the

Effect of environmental changes in the light/dark cycle on mood-related behavior

In human populations, it is known that disruptions in circadian rhythms, including the sleep/wake cycle, through environmental means can produce mood-related problems in vulnerable individuals. The impact of acute alterations in rhythms is evident to anyone who has experienced “jet lag” after a long flight across multiple time zones. A more chronic example is seasonal affective disorder (SAD) or “winter depression”, which is the most common of all mood disorders, affecting upwards of 10% of the

Stress and the disruption of circadian rhythms

Exposure to stressful life events in human populations has long been associated with increased bouts of depression (Birley, 1972, Grandin et al., 2006). The social zeitgeber theory of depression put forth by Ehlers et al. (1988) suggests that life events (usually stressful ones) disrupt the circadian cycle and in turn derail the internal circadian clock leading to depressive episodes in vulnerable individuals (Ehlers et al. 1988). A number of chronic stress models have been developed in animals

Circadian genes and SCN disruption alters mood

The few studies that have examined the impact of SCN lesions on mood-related behavior have yielded mixed results. Two separate studies found that bilateral SCN lesions in rats lead to a reduction in depression-related behavior in the FST (Arushanian and Popov, 1994, Tataroglu et al., 2004). However, a study by Tuma et al. found that lesions of the SCN had no effect on depression and anxiety-related behavior following social defeat stress, but SCN integrity was necessary for the effective

The metabolic link

Quite often mood disorders and their treatments are associated with an increased risk of metabolic disorders, eating disorders, and obesity (McIntyre, 2009). Metabolic disorders are also strongly associated with disruptions in the normal sleep/wake schedule (Bass and Takahashi, 2010), thus metabolic syndrome, circadian disruption, and depression are often co-morbid syndromes. Recently, it has become clear that several of the circulating peptides that control metabolic functions such as appetite

Antidepressant and mood stabilizers alter circadian rhythms

Several therapies that are utilized for the treatment of mood disorders are known to modulate circadian rhythms. Some antidepressant treatments have a phase-advancing effect on circadian rhythms. For example, morning bright light therapy leads to a phase advance in several rhythms in human subjects with SAD and the proper phase alignment in SAD either through light or melatonin treatment is necessary for therapeutic effects (Lewy et al., 2006, Lewy et al., 2007, Terman and Jiuan Su, 2010). In

Conclusions: it's all about timing!

A flurry of studies over the last few years using animal models has pointed to the circadian system as a critical modifier of mood-related behavior. While the circadian system is internally controlled, it is influenced strongly by the environment. Thus, alterations in the light cycle, availability (or overindulgence) of nutrients, and exposure to stress will all impact rhythms. The major mood- and reward-related circuits of the brain have their own endogenous rhythms that are organized by the

Role of the funding source

Ongoing studies in Dr. McClung's laboratory are funded by NIDA, NIMH, NINDS, The McKnight Foundation, NARSAD, and The Blue Gator Foundation. They supply the funding for specific projects as outlined in each specific grant applications. The funding sources are not involved in the writing or submission of this manuscript.

Contributor

Colleen A. McClung, Ph.D. is the only contributor.

Conflict of interest

C Mc C has received grants from GSK and Pfizer, honoraria from GSK, Pfizer and Servier and was on paid position at Orphagen.

The supplement that this article appears in was produced with an educational grant from Servier.

C Mc C received a fee from Servier for her work on this supplement.

Acknowledgements

I would like to thank Dr. John Enwright for the helpful comments on the manuscript and Dr. Laurent Coque for the artwork. Studies discussed from our group were funded by NIDA, NIMH, NINDS, The McKnight Foundation, NARSAD, and The Blue Gator Foundation.

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ReviewCircadian rhythms and mood regulation: Insights from pre-clinical models

Abstract

Section snippets

Introduction to circadian timing regulation

Effect of environmental changes in the light/dark cycle on mood-related behavior

Stress and the disruption of circadian rhythms

Circadian genes and SCN disruption alters mood

The metabolic link

Antidepressant and mood stabilizers alter circadian rhythms

Conclusions: it's all about timing!

Role of the funding source

Contributor

Conflict of interest

Acknowledgements

Cell

Behav. Brain Res.

J. Neurosci. Methods

Brain Res.

Neurosci. Lett.

J. Psychosom. Res.

Eur. Neuropsychopharmacol.

Brain Res. Rev.

Cell

Behav. Brain Res.

Psychiatry Res.

Neurobiol. Dis.

Behav. Brain Res.

Biol. Psychiatry

Clin. Psychol. Rev.

Curr. Biol.

Trends Neurosci.

Psychiatry Res.

Neuron

J. Biol. Chem.

Cell

Pharmacol. Ther.

Brain Res.

Cell Metab.

Cell

Neurosci. Res.

Biol. Psychiatry

Cell

Neurosci. Biobehav. Rev.

Prog. Neurobiol.

Cell

Psychoneuroendocrinology

Cocaine sensitization and reward are under the influence of circadian genes and rhythm

Proc. Natl. Acad. Sci. U. S. A.

Ghrelin modulates the activity and synaptic input organization of midbrain dopamine neurons while promoting appetite

J. Clin. Invest.

The effect of damage to the hypothalamic suprachiasmatic nuclei in rats on the dynamic short-period fluctuations of their normal and abnormal behaviors

Fiziol Zh Im I M Sechenova.

We are in the dark here: induction of depression- and anxiety-like behaviours in the diurnal fat sand rat, by short daylight or melatonin injections

Int. J. Neuropsychopharmacol.

Autorhythmometry in manic-depressives

Chronobiologia

Circadian integration of metabolism and energetics

Science

Influence of CLOCK gene polymorphism on circadian mood fluctuation and illness recurrence in bipolar depression

Am. J. Med. Genet. B Neuropsychiatr. Genet.

Mesolimbic dopamine neurons in the brain reward circuit mediate susceptibility to social defeat and antidepressant action

J. Neurosci.

Circadian clock control by SUMOylation of BMAL1

Science

Ghrelin's roles in stress, mood, and anxiety regulation

Int. J. Pept.

Psychiatric aspects of shiftwork

Occup. Med.

CLOCK and NPAS2 have overlapping roles in the suprachiasmatic circadian clock

Nat. Neurosci.

Lithium- and valproate-induced alterations in circadian locomotor behavior in Drosophila

Neuropsychopharmacology

In vivo assessment of the midbrain raphe nuclear regulation of serotonin release in the hamster suprachiasmatic nucleus

J. Neurophysiol.

Lithium ameliorates nucleus accumbens phase-signaling dysfunction in a genetic mouse model of mania

J. Neurosci.

The circadian Clock mutation increases exploratory activity and escape-seeking behavior

Genes Brain Behav.

In vivo resetting of the hamster circadian clock by 5-HT7 receptors in the suprachiasmatic nucleus

J. Neurosci.

Review
Circadian rhythms and mood regulation: Insights from pre-clinical models