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Chronobiological theories of mood disorder

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Abstract

Major depressive disorder (MDD) remains the most prevalent mental disorder and a leading cause of disability, affecting approximately 100 million adults worldwide. The disorder is characterized by a constellation of symptoms affecting mood, anxiety, neurochemical balance, sleep patterns, and circadian and/or seasonal rhythm entrainment. However, the mechanisms underlying the association between chronobiological parameters and depression remain unknown. A PubMed search was conducted to review articles from 1979 to the present, using the following search terms: “chronobiology,” “mood,” “sleep,” and “circadian rhythms.” We aimed to synthesize the literature investigating chronobiological theories of mood disorders. Current treatments primarily include tricyclic antidepressants and selective serotonin reuptake inhibitors, which are known to increase extracellular concentrations of monoamine neurotransmitters. However, these antidepressants do not treat the sleep disturbances or circadian and/or seasonal rhythm dysfunctions associated with depressive disorders. Several theories associating sleep and circadian rhythm disturbances with depression have been proposed. Current evidence supports the existence of associations between these, but the direction of causality remains elusive. Given the existence of chronobiological disturbances in depression and evidence regarding their treatment in improving depression, a chronobiological approach, including timely use of light and melatonin agonists, could complement the treatment of MDD.

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Fig. 1

Acknowledgment (publisher: John Wiley and Sons): Figure reprinted with permission from Borbély et al. 51. Copyright 2016. European Sleep Research Society. (License Number: 4180310623590 dated Sept 01, 2017)

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References

  1. Inouye ST, Kawamura H (1979) Persistence of circadian rhythmicity in a mammalian hypothalamic “island” containing the suprachiasmatic nucleus. Proc Natl Acad Sci USA 76(11):5962–5966

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Reiter RJ (1993) The melatonin rhythm: both a clock and a calendar. Experientia 49(8):654–664

    Article  CAS  PubMed  Google Scholar 

  3. Turek FW (2007) From circadian rhythms to clock genes in depression. Int Clin Psychopharmacol 22:S1–S8

    Article  PubMed  Google Scholar 

  4. van den Pol AN (1980) The hypothalamic suprachiasmatic nucleus of rat: intrinsic anatomy. J Comp Neurol 191(4):661–702

    Article  PubMed  Google Scholar 

  5. Schibler U (2017) Interaction between central and peripheral clocks in mammals. In: Vinod K (ed) Biological timekeeping: clocks, rhythms and behaviour. Springer, New Delhi, India, pp 337–363

    Chapter  Google Scholar 

  6. Hermanstyne TO, Simms CL, Carrasquillo Y, Herzog ED, Nerbonne JM (2016) Distinct firing properties of vasoactive intestinal peptide-expressing neurons in the suprachiasmatic nucleus. J Biol Rhythms 31(1):57–67

    Article  CAS  PubMed  Google Scholar 

  7. Brown GM, McIntyre RS, Rosenblat J, Hardeland R (2017) Depressive disorders: Processes leading to neurogeneration and potential novel treatments. Progr Neuro-Psychopharmacol Biol Psychiatry. doi:10.1016/j.pnpbp.2017.04.023

    Google Scholar 

  8. Mrosovsky N, Hattar S (2003) Impaired masking responses to light in melanopsin-knockout mice. Chronobiol Int 20(6):989–999

    Article  CAS  PubMed  Google Scholar 

  9. Berson DM, Dunn FA, Takao M (2002) Phototransduction by retinal ganglion cells that set the circadian clock. Science 295(5557):1070–1073

    Article  CAS  PubMed  Google Scholar 

  10. Moore RY, Speh JC (2004) Serotonin innervation of the primate suprachiasmatic nucleus. Brain Res 1010(1):169–173

    Article  CAS  PubMed  Google Scholar 

  11. Stehle JH, von Gall C, Korf HW (2003) Melatonin: a clock-output, a clock-input. J Neuroendocrinol 15(4):383–389

    Article  CAS  PubMed  Google Scholar 

  12. Richter CP (1960) Biological clocks in medicine and psychiatry: shock-phase hypothesis. Proc Natl Acad Sci USA 46(11):1506–1530

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Cuesta M, Cermakian N, Boivin DB (2013) Circadian clock genes and psychiatric disorders. In: The genetic basis of sleep and sleep disorders. University of Cambridge Press, Cambridge, pp 351–364

    Chapter  Google Scholar 

  14. Bollettini I, Melloni EM, Aggio V, Poletti S, Lorenzi C, Pirovano A et al (2017) Clock genes associate with white matter integrity in depressed bipolar patients. Chronobiol Int 34(2):212–224

    Article  CAS  PubMed  Google Scholar 

  15. Dallaspezia S, Locatelli C, Lorenzi C, Pirovano A, Colombo C, Benedetti F (2016) Sleep homeostatic pressure and PER3 VNTR gene polymorphism influence antidepressant response to sleep deprivation in bipolar depression. J Affect Disord 192:64–69

    Article  CAS  PubMed  Google Scholar 

  16. Darien I (2014) International classification of sleep disorders. Am Acad Sleep Med

  17. Hasler G, Drevets WC, Manji HK, Charney DS (2004) Discovering endophenotypes for major depression. Neuropsychopharmacology 29(10):1765–1781

    Article  CAS  PubMed  Google Scholar 

  18. Matsubara T, Matsuo K, Harada K, Nakano M, Nakashima M, Watanuki T et al (2016) Distinct and shared endophenotypes of neural substrates in bipolar and major depressive disorders. PLoS One 11(12):e0168493

    Article  PubMed  PubMed Central  Google Scholar 

  19. Misiak B, Frydecka D, Rybakowski JK (2016) Editorial: endophenotypes for schizophrenia and mood disorders: implications from genetic, biochemical, cognitive, behavioral, and neuroimaging studies. Front Psychiatry 7:83

    Article  PubMed  PubMed Central  Google Scholar 

  20. Dudley TE, DiNardo LA, Glass JD (1998) Endogenous regulation of serotonin release in the hamster suprachiasmatic nucleus. J Neurosci 18(13):5045–5052

    CAS  PubMed  Google Scholar 

  21. Pontes ALBd, Engelberth RCGJ, Nascimento EdS Jr, Cavalcante JC, Costa MSMdO, Pinato L et al (2010) Serotonin and circadian rhythms. Psychol Neurosci 3(2):217–228

    Article  Google Scholar 

  22. Takeuchi K, Mohammad S, Ozaki T, Morioka E, Kawaguchi K, Kim J et al (2014) Serotonin-2C receptor involved serotonin-induced Ca2+ mobilisations in neuronal progenitors and neurons in rat suprachiasmatic nucleus. Sci Rep 4

  23. Mansour HA, Wood J, Logue T, Chowdari KV, Dayal M, Kupfer DJ 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  CAS  PubMed  Google Scholar 

  24. Albrecht U (2013) Circadian clocks and mood-related behaviors. Handb Exp Pharmacol 217:227–239

    Article  CAS  Google Scholar 

  25. McClung CA (2011) Circadian rhythms and mood regulation: insights from pre-clinical models. Eur Neuropsychopharmacol 21:S683–S693

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Chung S, Lee EJ, Yun S, Choe HK, Park S-B, Son HJ et al (2014) Impact of circadian nuclear receptor REV-ERBα on midbrain dopamine production and mood regulation. Cell 157(4):858–868

    Article  CAS  PubMed  Google Scholar 

  27. Shi J, Wittke-Thompson JK, Badner JA, Hattori E, Potash JB, Willour VL et al (2008) Clock genes may influence bipolar disorder susceptibility and dysfunctional circadian rhythm. Am J Med Genet Part B Neuropsychiatr Genet 147(7):1047–1055

    Article  Google Scholar 

  28. Van Cauter E, Turek FW (1986) Depression: a disorder of timekeeping? Perspect Biol Med 29(4):510–520

    Article  PubMed  Google Scholar 

  29. American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders (DSM-5®). American Psychiatric Pub, Arlington County, Virginia, US

    Book  Google Scholar 

  30. Ohayon MM (2007) Insomnia: a ticking clock for depression?. Pergamon, Oxford

    Google Scholar 

  31. David Nutt D, Paterson L (2008) Sleep disorders as core symptoms of depression. Dialogues Clin Neurosci 10(3):329–336

    PubMed  PubMed Central  Google Scholar 

  32. Armitage R (1995) Microarchitectural findings in sleep EEG in depression: diagnostic implications. Biol Psychiat 37(2):72–84

    Article  CAS  PubMed  Google Scholar 

  33. Pandi-Perumal SR, Moscovitch A, Srinivasan V, Spence DW, Cardinali DP, Brown GM (2009) Bidirectional communication between sleep and circadian rhythms and its implications for depression: lessons from agomelatine. Prog Neurobiol 88(4):264–271

    Article  CAS  PubMed  Google Scholar 

  34. Armitage R, Hoffmann R, Trivedi M, Rush AJ (2000) Slow-wave activity in NREM sleep: sex and age effects in depressed outpatients and healthy controls. Psychiatry Res 95(3):201–213

    Article  CAS  PubMed  Google Scholar 

  35. Van den Hoofdakker R (1994) Chronobiological theories of nonseasonal affective disorders and their implications for treatment. J Biol Rhythms 9(2):157–183

    Article  PubMed  Google Scholar 

  36. Ben-Hamo M, Larson TA, Duge LS, Sikkema C, Wilkinson CW, Horacio O et al (2016) Circadian forced desynchrony of the master clock leads to phenotypic manifestation of depression in rats. eNeuro 3(6):ENEURO. 0237-16.2016

    Article  PubMed  Google Scholar 

  37. Borbély AA (1982) A two process model of sleep regulation. Hum Neurobiol 1(3):195–204

    PubMed  Google Scholar 

  38. Kripke DF, Elliott JA, Welsh DK, Youngstedt SD (2015) Photoperiodic and circadian bifurcation theories of depression and mania. F1000Research 4

  39. Daan S, Beersma D, Borbély AA (1984) Timing of human sleep: recovery process gated by a circadian pacemaker. Am J Physiol Regul Integr Comp Physiol 246(2):R161–R183

    Article  CAS  Google Scholar 

  40. Monteleone P, Maj M (2008) The circadian basis of mood disorders: recent developments and treatment implications. Eur Neuropsychopharmacol 18(10):701–711

    Article  CAS  PubMed  Google Scholar 

  41. Cervantes P, Gelber S, Ng YK (2001) Circadian secretion of cortisol in bipolar disorder. J Psychiatry Neurosci Jpn 26(5):411

    CAS  PubMed  Google Scholar 

  42. Nurnberger JI, Adkins S, Lahiri DK, Mayeda A, Hu K, Lewy A et al (2000) Melatonin suppression by light in euthymic bipolar and unipolar patients. Arch Gen Psychiatry 57(6):572–579

    Article  CAS  PubMed  Google Scholar 

  43. Landgraf D, McCarthy MJ, Welsh DK (2014) The role of the circadian clock in animal models of mood disorders. Behav Neurosci 128(3):344

    Article  PubMed  Google Scholar 

  44. Wehr TA, Wirz-Justice A (1980) Internal coincidence model for sleep deprivation and depression. Sleep 26:33

    Google Scholar 

  45. St Hilaire MA, Gooley JJ, Khalsa SBS, Kronauer RE, Czeisler CA, Lockley SW (2012) Human phase response curve to a 1 h pulse of bright white light. J Physiol 590(13):3035–3045

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Germain A, Kupfer DJ (2008) Circadian rhythm disturbances in depression. Hum Psychopharmacol Clin Exp 23(7):571–585

    Article  Google Scholar 

  47. Reinberg A, Ashkenazi I (2008) Internal desynchronization of circadian rhythms and tolerance to shift work. Chronobiol Int 25(4):625–643

    Article  PubMed  Google Scholar 

  48. Boivin DB (2000) Influence of sleep-wake and circadian rhythm disturbances in psychiatric disorders. J Psychiatry Neurosci 25(5):446–458

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Chellappa SL, Schröder C, Cajochen C (2009) Chronobiology, excessive daytime sleepiness and depression: is there a link? Sleep Med 10(5):505–514

    Article  PubMed  Google Scholar 

  50. Borbély A (1987) The S-deficiency hypothesis of depression and the two-process model of sleep regulation. Pharmacopsychiatry 20(01):23–29

    Article  PubMed  Google Scholar 

  51. Borbély AA, Daan S, Wirz-Justice A, Deboer T (2016) The two-process model of sleep regulation: a reappraisal. J Sleep Res 25:131–143

    Article  PubMed  Google Scholar 

  52. Berger M, Riemann D (1993) REM sleep in depression—an overview. J Sleep Res 2(4):211–223

    Article  CAS  PubMed  Google Scholar 

  53. Monteleone P, Maj M (2009) Circadian rhythm disturbances in depression: implications for treatment and quality of remission. Medicographia 31(2):132–139

    Google Scholar 

  54. Adrien J (2002) Neurobiological bases for the relation between sleep and depression. Sleep Med Rev 6(5):341–351

    Article  PubMed  Google Scholar 

  55. Akiskal HS (2016) Mood disturbances. The medical basis of psychiatry. Springer, Berlin, pp 459–475

    Book  Google Scholar 

  56. Ehlers CL, Frank E, Kupfer DJ (1988) Social zeitgebers and biological rhythms: a unified approach to understanding the etiology of depression. Arch Gen Psychiatry 45(10):948–952

    Article  CAS  PubMed  Google Scholar 

  57. Monk TK, Flaherty JF, Frank E, Hoskinson K, Kupfer DJ (1990) The social rhythm metric: an instrument to quantify the daily rhythms of life. J Nerv Mental Dis 178(2):120–126

    Article  CAS  Google Scholar 

  58. Monk TH, Kupfer DJ, Frank E, Ritenour AM (1991) The Social Rhythm Metric (SRM): measuring daily social rhythms over 12 weeks. Psychiatry Res 36(2):195–207

    Article  CAS  PubMed  Google Scholar 

  59. Monk TH (2010) Enhancing circadian zeitgebers. Sleep 33(4):421

    Article  PubMed  PubMed Central  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  61. Parry BL, Meliska CJ, Sorenson DL, Lopez AM, Martinez LF, Nowakowski S et al (2008) Plasma melatonin circadian rhythm disturbances during pregnancy and postpartum in depressed women and women with personal or family histories of depression. Am J Psychiatry 165(12):1551–1558

    Article  PubMed  PubMed Central  Google Scholar 

  62. Simpson W, Frey BN, Steiner M (2016) Mild depressive symptoms during the third trimester of pregnancy are associated with disruptions in daily rhythms but not subjective sleep quality. J Women Health 25(6):594–598

    Article  Google Scholar 

  63. Parry BL (2016) Rhythms and Blues. J Women Health 2002 25(6):563–564

    Article  Google Scholar 

  64. Sharkey KM, Pearlstein TB, Carskadon MA (2013) Circadian phase shifts and mood across the perinatal period in women with a history of major depressive disorder: a preliminary communication. J Affect Disord 150(3):1103–1108

    Article  PubMed  PubMed Central  Google Scholar 

  65. Meliska CJ, Martinez LF, Lopez AM, Sorenson DL, Nowakowski S, Parry BL (2011) Relationship of morningness-eveningness questionnaire score to melatonin and sleep timing, body mass index and atypical depressive symptoms in peri- and post-menopausal women. Psychiatry Res 188(1):88–95

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  66. Kripke DF, Elliott JA, Youngstedt SD, Parry BL, Hauger RL, Rex KM (2010) Weak evidence of bright light effects on human LH and FSH. J Circadian Rhythms 8:5

    Article  PubMed  PubMed Central  Google Scholar 

  67. Golden RN, Gaynes BN, Ekstrom RD, Hamer RM, Jacobsen FM, Suppes T et al (2005) The efficacy of light therapy in the treatment of mood disorders: a review and meta-analysis of the evidence. Am J Psychiatry 162(4):656–662

    Article  PubMed  Google Scholar 

  68. Wirz-Justice A, Benedetti F, Berger M, Lam RW, Martiny K, Terman M et al (2005) Chronotherapeutics (light and wake therapy) in affective disorders. Psychol Med 35(07):939–944

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Psychiatry, Faculty of Medicine, Mansoura University, Mansoura, Egypt

    Nevin F. W. Zaki

  2. 652 Dufferin Street, Toronto, ON, M6K 2B4, Canada

    David Warren Spence

  3. University Sleep Disorders Center, College of Medicine, King Saud University, Riyadh, Saudi Arabia

    Ahmed S. BaHammam

  4. Somnogen Canada Inc, Toronto, ON, Canada

    Seithikurippu R. Pandi-Perumal

  5. BIOMED-UCA-CONICET and Department of Teaching and Research, Faculty of Medical Sciences, Pontificia Universidad Católica Argentina, Buenos Aires, Argentina

    Daniel P. Cardinali

  6. Department of Psychiatry, Centre for Addiction and Mental Health, University of Toronto, Toronto, ON, M5T 1R8, Canada

    Gregory M. Brown

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  1. Nevin F. W. Zaki
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  2. David Warren Spence
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  3. Ahmed S. BaHammam
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Correspondence to Nevin F. W. Zaki.

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Zaki, N.F.W., Spence, D.W., BaHammam, A.S. et al. Chronobiological theories of mood disorder. Eur Arch Psychiatry Clin Neurosci 268, 107–118 (2018). https://doi.org/10.1007/s00406-017-0835-5

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  • DOI: https://doi.org/10.1007/s00406-017-0835-5

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