Skip to main content
SpringerLink
Log in

Circadian Clocks and Mood-Related Behaviors

  • Chapter
  • First Online:
Circadian Clocks

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 217))

Abstract

Circadian clocks are present in nearly all tissues of an organism, including the brain. The brain is not only the site of the master coordinator of circadian rhythms located in the suprachiasmatic nuclei (SCN) but also contains SCN-independent oscillators that regulate various functions such as feeding and mood-related behavior. Understanding how clocks receive and integrate environmental information and in turn control physiology under normal conditions is of importance because chronic disturbance of circadian rhythmicity can lead to serious health problems. Genetic modifications leading to disruption of normal circadian gene functions have been linked to a variety of psychiatric conditions including depression, seasonal affective disorder, eating disorders, alcohol dependence, and addiction. It appears that clock genes play an important role in limbic regions of the brain and influence the development of drug addiction. Furthermore, analyses of clock gene polymorphisms in diseases of the central nervous system (CNS) suggest a direct or indirect influence of circadian clock genes on brain function. In this chapter, I will present evidence for a circadian basis of mood disorders and then discuss the involvement of clock genes in such disorders. The relationship between metabolism and mood disorders is highlighted followed by a discussion of how mood disorders may be treated by changing the circadian cycle.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 349.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 449.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 449.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Abarca C, Albrecht U, Spanagel R (2002) Cocaine sensitization and reward are under the influence of circadian genes and rhythm. Proc Natl Acad Sci USA 99(13):9026–9030

    Article  PubMed  CAS  Google Scholar 

  • Akhisaroglu M et al (2005) Diurnal rhythms in quinpirole-induced locomotor behaviors and striatal D2/D3 receptor levels in mice. Pharmacol Biochem Behav 80(3):371–377

    Article  PubMed  CAS  Google Scholar 

  • Atkinson M, Kripke DF, Wolf SR (1975) Autorhythmometry in manic-depressives. Chronobiologia 2(4):325–335

    PubMed  CAS  Google Scholar 

  • Benedetti F et al (2003) Influence of CLOCK gene polymorphism on circadian mood fluctuation and illness recurrence in bipolar depression. Am J Med Genet B Neuropsychiatr Genet 123B(1):23–26

    Article  PubMed  Google Scholar 

  • Benedetti F et al (2008) A length polymorphism in the circadian clock gene Per3 influences age at onset of bipolar disorder. Neurosci Lett 445(2):184–187

    Article  PubMed  CAS  Google Scholar 

  • Castaneda TR et al (2004) Circadian rhythms of dopamine, glutamate and GABA in the striatum and nucleus accumbens of the awake rat: modulation by light. J Pineal Res 36(3):177–185

    Article  PubMed  CAS  Google Scholar 

  • Challet E et al (2001) Sleep deprivation decreases phase-shift responses of circadian rhythms to light in the mouse: role of serotonergic and metabolic signals. Brain Res 909(1–2):81–91

    Article  PubMed  CAS  Google Scholar 

  • Coon SL et al (1997) Regulation of pineal alpha1B-adrenergic receptor mRNA: day/night rhythm and beta-adrenergic receptor/cyclic AMP control. Mol Pharmacol 51(4):551–557

    PubMed  CAS  Google Scholar 

  • DeBruyne JP, Weaver DR, Reppert SM (2007a) Peripheral circadian oscillators require CLOCK. Curr Biol 17(14):R538–R539

    Article  PubMed  CAS  Google Scholar 

  • DeBruyne JP, Weaver DR, Reppert SM (2007b) CLOCK and NPAS2 have overlapping roles in the suprachiasmatic circadian clock. Nat Neurosci 10(5):543–545

    Article  PubMed  CAS  Google Scholar 

  • Dong L et al (2011) Effects of the circadian rhythm gene period 1 (per1) on psychosocial stress-induced alcohol drinking. Am J Psychiatry 168(10):1090–1098

    Article  PubMed  Google Scholar 

  • Dzirasa K et al (2010) Lithium ameliorates nucleus accumbens phase-signaling dysfunction in a genetic mouse model of mania. J Neurosci 30(48):16314–16323

    Article  PubMed  CAS  Google Scholar 

  • Ebert D, Berger M (1998) Neurobiological similarities in antidepressant sleep deprivation and psychostimulant use: a psychostimulant theory of antidepressant sleep deprivation. Psychopharmacology 140(1):1–10

    Article  PubMed  CAS  Google Scholar 

  • Ehlen JC, Grossman GH, Glass JD (2001) In vivo resetting of the hamster circadian clock by 5-HT7 receptors in the suprachiasmatic nucleus. J Neurosci 21(14):5351–5357

    PubMed  CAS  Google Scholar 

  • Emens J et al (2009) Circadian misalignment in major depressive disorder. Psychiatry Res 168(3): 259–261

    Article  PubMed  Google Scholar 

  • Fitzgerald PJ et al (2010) Does gene deletion of AMPA GluA1 phenocopy features of schizoaffective disorder? Neurobiol Dis 40(3):608–621

    Article  PubMed  CAS  Google Scholar 

  • Frank E, Swartz HA, Kupfer DJ (2000) Interpersonal and social rhythm therapy: managing the chaos of bipolar disorder. Biol Psychiatry 48(6):593–604

    Article  PubMed  CAS  Google Scholar 

  • Grant D et al (2010) GSK4112, a small molecule chemical probe for the cell biology of the nuclear heme receptor Rev-erb alpha. ACS Chem Biol 5(10):925–932

    Article  PubMed  CAS  Google Scholar 

  • Grassi Zucconi G et al (2006) ‘One night’ sleep deprivation stimulates hippocampal neurogenesis. Brain Res Bull 69(4):375–381

    Article  PubMed  Google Scholar 

  • Guilding C, Piggins HD (2007) Challenging the omnipotence of the suprachiasmatic timekeeper: are circadian oscillators present throughout the mammalian brain? Eur J Neurosci 25(11): 3195–3216

    Article  PubMed  Google Scholar 

  • Hafen T, Wollnik F (1994) Effect of lithium carbonate on activity level and circadian period in different strains of rats. Pharmacol Biochem Behav 49(4):975–983

    Article  PubMed  CAS  Google Scholar 

  • Hampp G et al (2008) Regulation of monoamine oxidase A by circadian-clock components implies clock influence on mood. Curr Biol 18(9):678–683

    Article  PubMed  CAS  Google Scholar 

  • Hasler BP et al (2010) Phase relationships between core body temperature, melatonin, and sleep are associated with depression severity: further evidence for circadian misalignment in non-seasonal depression. Psychiatry Res 178(1):205–207

    Article  PubMed  CAS  Google Scholar 

  • Herxheimer A (2005) Jet lag. Clin Evid 13:2178–2183

    PubMed  Google Scholar 

  • Hirota T et al (2010) High-throughput chemical screen identifies a novel potent modulator of cellular circadian rhythms and reveals CKI alpha as a clock regulatory kinase. PLoS Biol 8(12):e1000559

    Article  PubMed  CAS  Google Scholar 

  • Hirota T et al (2012) Identification of small molecule activators of cryptochrome. Science 337: 1094–1097

    Article  PubMed  CAS  Google Scholar 

  • Hlastala SA, Frank E (2006) Adapting interpersonal and social rhythm therapy to the developmental needs of adolescents with bipolar disorder. Dev Psychopathol 18(4):1267–1288

    Article  PubMed  Google Scholar 

  • Hood S et al (2010) Endogenous dopamine regulates the rhythm of expression of the clock protein PER2 in the rat dorsal striatum via daily activation of D2 dopamine receptors. J Neurosci 30(42):14046–14058

    Article  PubMed  CAS  Google Scholar 

  • Iitaka C et al (2005) A role for glycogen synthase kinase-3beta in the mammalian circadian clock. J Biol Chem 280(33):29397–29402

    Article  PubMed  CAS  Google Scholar 

  • Johnsson A et al (1983) Period lengthening of human circadian rhythms by lithium carbonate, a prophylactic for depressive disorders. Int J Chronobiol 8(3):129–147

    PubMed  CAS  Google Scholar 

  • Kafka MS et al (1983) Circadian rhythms in rat brain neurotransmitter receptors. Fed Proc 42(11): 2796–2801

    PubMed  CAS  Google Scholar 

  • Kennaway DJ (2010) Clock genes at the heart of depression. J Psychopharmacol 24(2 Suppl):5–14

    Article  PubMed  CAS  Google Scholar 

  • King DP et al (1997) Positional cloning of the mouse circadian clock gene. Cell 89(4):641–653

    Article  PubMed  CAS  Google Scholar 

  • Klemfuss H (1992) Rhythms and the pharmacology of lithium. Pharmacol Ther 56(1):53–78

    Article  PubMed  CAS  Google Scholar 

  • Kojetin D et al (2011) Identification of SR8278, a synthetic antagonist of the nuclear heme receptor REV-ERB. ACS Chem Biol 6(2):131–134

    Article  PubMed  CAS  Google Scholar 

  • Kripke DF et al (1978) Circadian rhythm disorders in manic-depressives. Biol Psychiatry 13(3): 335–351

    PubMed  CAS  Google Scholar 

  • Kumar N et al (2010) Regulation of adipogenesis by natural and synthetic REV-ERB ligands. Endocrinology 151(7):3015–3025

    Article  PubMed  CAS  Google Scholar 

  • Kumar N et al (2011) Identification of SR3335 (ML-176): a synthetic ROR alpha selective inverse agonist. ACS Chem Biol 6(3):218–222

    Article  PubMed  CAS  Google Scholar 

  • Lavebratt C et al (2010) CRY2 is associated with depression. PLoS One 5(2):e9407

    Article  PubMed  Google Scholar 

  • Lewy AJ et al (1998) Morning vs. evening light treatment of patients with winter depression. Arch Gen Psychiatry 55(10):890–896

    Article  PubMed  CAS  Google Scholar 

  • Li J et al (2012) Lithium impacts on the amplitude and period of the molecular circadian clockwork. PLoS One 7(3):e33292

    Article  PubMed  CAS  Google Scholar 

  • Lisman J, Buzsaki G (2008) A neural coding scheme formed by the combined function of gamma and theta oscillations. Schizophr Bull 34(5):974–980

    Article  PubMed  Google Scholar 

  • Lopez-Rodriguez F, Kim J, Poland RE (2004) Total sleep deprivation decreases immobility in the forced-swim test. Neuropsychopharmacology 29(6):1105–1111

    Article  PubMed  CAS  Google Scholar 

  • Magnusson A, Boivin D (2003) Seasonal affective disorder: an overview. Chronobiol Int 20(2): 189–207

    Article  PubMed  Google Scholar 

  • Mansour HA et al (2006) Association study of eight circadian genes with bipolar I disorder, schizoaffective disorder and schizophrenia. Genes Brain Behav 5(2):150–157

    Article  PubMed  CAS  Google Scholar 

  • McCarthy MJ et al (2012) A survey of genomic studies supports association of circadian clock genes with bipolar disorder spectrum illnesses and lithium response. PLoS One 7(2):e32091

    Article  PubMed  CAS  Google Scholar 

  • McClung CA (2007) Circadian genes, rhythms and the biology of mood disorders. Pharmacol Ther 114(2):222–232

    Article  PubMed  CAS  Google Scholar 

  • McClung CA et al (2005) Regulation of dopaminergic transmission and cocaine reward by the Clock gene. Proc Natl Acad Sci USA 102(26):9377–9381

    Article  PubMed  CAS  Google Scholar 

  • McIntyre RS (2009) Managing weight gain in patients with severe mental illness. J Clin Psychiatry 70(7):e23

    Article  PubMed  Google Scholar 

  • Meng QJ et al (2010) Entrainment of disrupted circadian behavior through inhibition of casein kinase 1 (CK1) enzymes. Proc Natl Acad Sci USA 107(34):15240–15245

    Article  PubMed  CAS  Google Scholar 

  • Mukherjee S et al (2010) Knockdown of Clock in the ventral tegmental area through RNA interference results in a mixed state of mania and depression-like behavior. Biol Psychiatry 68(6):503–511

    Article  PubMed  CAS  Google Scholar 

  • Nakahata Y et al (2009) Circadian control of the NAD+ salvage pathway by CLOCK-SIRT1. Science 324(5927):654–657

    Article  PubMed  CAS  Google Scholar 

  • Nievergelt CM et al (2006) Suggestive evidence for association of the circadian genes PERIOD3 and ARNTL with bipolar disorder. Am J Med Genet B Neuropsychiatr Genet 141B(3): 234–241

    Article  PubMed  CAS  Google Scholar 

  • Pandi-Perumal SR et al (2006) Melatonin: nature’s most versatile biological signal? FEBS J 273(13):2813–2838

    Article  PubMed  CAS  Google Scholar 

  • Partonen T et al (2007) Three circadian clock genes Per2, Arntl, and Npas2 contribute to winter depression. Ann Med 39(3):229–238

    Article  PubMed  CAS  Google Scholar 

  • Prickaerts J et al (2006) Transgenic mice overexpressing glycogen synthase kinase 3beta: a putative model of hyperactivity and mania. J Neurosci 26(35):9022–9029

    Article  PubMed  CAS  Google Scholar 

  • Ramsey KM et al (2009) Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis. Science 324(5927):651–654

    Article  PubMed  CAS  Google Scholar 

  • Roybal K et al (2007) Mania-like behavior induced by disruption of CLOCK. Proc Natl Acad Sci USA 104(15):6406–6411

    Article  PubMed  CAS  Google Scholar 

  • Rutter J et al (2001) Regulation of clock and NPAS2 DNA binding by the redox state of NAD cofactors. Science 293(5529):510–514

    Article  PubMed  CAS  Google Scholar 

  • Sahar S et al (2011) Altered behavioral and metabolic circadian rhythms in mice with disrupted NAD+ oscillation. Aging 3(8):794–802

    PubMed  Google Scholar 

  • Schmutz I et al (2010) The mammalian clock component PERIOD2 coordinates circadian output by interaction with nuclear receptors. Genes Dev 24(4):345–357

    Article  PubMed  CAS  Google Scholar 

  • Scott AJ (2000) Shift work and health. Prim Care 27(4):1057–1079

    Article  PubMed  CAS  Google Scholar 

  • Serretti A et al (2003) Genetic dissection of psychopathological symptoms: insomnia in mood disorders and CLOCK gene polymorphism. Am J Med Genet B Neuropsychiatr Genet 121B(1): 35–38

    Article  PubMed  Google Scholar 

  • Shirayama M et al (2003) The psychological aspects of patients with delayed sleep phase syndrome (DSPS). Sleep Med 4(5):427–433

    Article  PubMed  Google Scholar 

  • Solt LA et al (2012) Regulation of circadian behavior and metabolism by synthetic REV-ERB agonists. Nature 485:62–68

    Article  PubMed  CAS  Google Scholar 

  • Souetre E et al (1989) Circadian rhythms in depression and recovery: evidence for blunted amplitude as the main chronobiological abnormality. Psychiatry Res 28(3):263–278

    Article  PubMed  CAS  Google Scholar 

  • Spanagel R et al (2005) The clock gene Per2 influences the glutamatergic system and modulates alcohol consumption. Nat Med 11(1):35–42

    Article  PubMed  CAS  Google Scholar 

  • Spencer S et al (2012) A mutation in CLOCK leads to altered dopamine receptor function. J Neurochem 123:124–134

    Article  PubMed  CAS  Google Scholar 

  • Sprouse J, Braselton J, Reynolds L (2006) Fluoxetine modulates the circadian biological clock via phase advances of suprachiasmatic nucleus neuronal firing. Biol Psychiatry 60(8):896–899

    Article  PubMed  CAS  Google Scholar 

  • Terman M, Terman JS (2005) Light therapy for seasonal and nonseasonal depression: efficacy, protocol, safety, and side effects. CNS Spectr 10(8):647–663; quiz 672

    Google Scholar 

  • Turek FW et al (2005) Obesity and metabolic syndrome in circadian Clock mutant mice. Science 308(5724):1043–1045

    Article  PubMed  CAS  Google Scholar 

  • Van Reeth O et al (1997) Comparative effects of a melatonin agonist on the circadian system in mice and Syrian hamsters. Brain Res 762(1–2):185–194

    Article  PubMed  Google Scholar 

  • Vitaterna MH et al (1994) Mutagenesis and mapping of a mouse gene, Clock, essential for circadian behavior. Science 264(5159):719–725

    Article  PubMed  CAS  Google Scholar 

  • Walton KM et al (2009) Selective inhibition of casein kinase 1 epsilon minimally alters circadian clock period. J Pharmacol Exp Ther 330(2):430–439

    Article  PubMed  CAS  Google Scholar 

  • Wang Y et al (2010) Identification of SR1078, a synthetic agonist for the orphan nuclear receptors ROR alpha and ROR gamma. ACS Chem Biol 5(11):1029–1034

    Article  PubMed  CAS  Google Scholar 

  • Wang X et al (2012) A promoter polymorphism in the Per3 gene is associated with alcohol and stress response. Transl Psychiatry 2:e73

    Article  PubMed  CAS  Google Scholar 

  • Weber M et al (2004) Circadian patterns of neurotransmitter related gene expression in motor regions of the rat brain. Neurosci Lett 358(1):17–20

    Article  PubMed  CAS  Google Scholar 

  • Weiner N et al (1992) Circadian and seasonal rhythms of 5-HT receptor subtypes, membrane anisotropy and 5-HT release in hippocampus and cortex of the rat. Neurochem Int 21(1):7–14

    Article  PubMed  CAS  Google Scholar 

  • Wirz-Justice A, Van den Hoofdakker RH (1999) Sleep deprivation in depression: what do we know, where do we go? Biol Psychiatry 46(4):445–453

    Article  PubMed  CAS  Google Scholar 

  • Wu JC et al (2009) Rapid and sustained antidepressant response with sleep deprivation and chronotherapy in bipolar disorder. Biol Psychiatry 66(3):298–301

    Article  PubMed  CAS  Google Scholar 

  • Xu Y et al (2005) Functional consequences of a CKIdelta mutation causing familial advanced sleep phase syndrome. Nature 434(7033):640–644

    Article  PubMed  CAS  Google Scholar 

  • Yang X et al (2006) Nuclear receptor expression links the circadian clock to metabolism. Cell 126(4):801–810

    Article  PubMed  CAS  Google Scholar 

  • Yin L et al (2006) Nuclear receptor Rev-erb alpha is a critical lithium-sensitive component of the circadian clock. Science 311(5763):1002–1005

    Article  PubMed  CAS  Google Scholar 

  • Yin L et al (2007) Rev-erb alpha, a heme sensor that coordinates metabolic and circadian pathways. Science 318(5857):1786–1789

    Article  PubMed  CAS  Google Scholar 

  • Zghoul T et al (2007) Ethanol self-administration and reinstatement of ethanol-seeking behavior in Per1(Brdm1) mutant mice. Psychopharmacology 190(1):13–19

    Article  PubMed  CAS  Google Scholar 

  • Zheng B et al (1999) The mPer2 gene encodes a functional component of the mammalian circadian clock. Nature 400(6740):169–173

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

I would like to thank Dr. Jürgen Ripperger for his comments on the manuscript. Financial support from the Swiss National Science Foundation and the State of Fribourg is gratefully acknowledged.

Author information

Authors and Affiliations

  1. Department of Biology, Unit of Biochemistry, University of Fribourg, Chemin du Musée 5, 1700, Fribourg, Switzerland

    Urs Albrecht

Authors
  1. Urs Albrecht
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Urs Albrecht .

Editor information

Editors and Affiliations

  1. , Laboratory of Chronobiology, Charité Universiätsmedizin Berlin, Hessische Str. 3-4, Berlin, 10115, Germany

    Achim Kramer

  2. Ludwig-Maximilians-Universität München, Institute of Medical Psychology, Goethestrasse 31/ I, München, 80336, Germany

    Martha Merrow

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Albrecht, U. (2013). Circadian Clocks and Mood-Related Behaviors. In: Kramer, A., Merrow, M. (eds) Circadian Clocks. Handbook of Experimental Pharmacology, vol 217. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-25950-0_9

Download citation

Publish with us

Policies and ethics

Search

Navigation