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Rapid eye movement (REM) sleep: An endophenotype for depression

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Abstract

Disturbed sleep is one of the hallmark signs of depression. After successful treatment, many of these signs disappear; however, changes in rapid eye movement (REM) sleep may persist and even predict recurrence of depression. High-risk studies have established these alterations to be not only biological scars but true endophenotypes for depression. REM sleep changes are mediated by the noradrenergic, serotonergic, and cholinergic systems and are under strong genetic control. REM sleep has a crucial role for brain maturation and is inhibited during ontogeny. Lack of this inhibition may predispose an individual to depression. Findings regarding the CREB gene support REM sleep’s role in depression. The combination of psychopathology and neurobiological measures, such as REM sleep parameters, will help to improve genetic studies and therefore increase the knowledge of relevant pathways for depression. This could facilitate development of preventive and therapeutic measures.

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References and Recommended Reading

  1. Gresham SC, Agnew HW, William RL: The sleep of depressed patients. An EEG and eye movement study. Arch Gen Psychiatry 1965, 13:503–507.

    PubMed  CAS  Google Scholar 

  2. Benca RM, Obermeyer WH, Thisted RA, et al.: Sleep and psychiatric disorder. A meta-analysis. Arch Gen Psychiatry 1992, 49:651–668.

    PubMed  CAS  Google Scholar 

  3. Kupfer DJ, Foster FG, Coble P, et al.: The application of EEG sleep for the differential diagnosis of affective disorders. Am J Psychiatry 1978, 135:68–74.

    Google Scholar 

  4. Reynolds CF, Kupfer DJ: Sleep research in affective illness: state of the art circa 1987. Sleep 1987, 10:199–215.

    PubMed  Google Scholar 

  5. Steiger A, von Bardeleben U, Herth T, et al.: Sleep-EEG and nocturnal secretion of cortisol and human growth hormone in male patients with endogenous depression before treatment and after recovery. J Affect Disord 1989, 16:189–195.

    Article  PubMed  CAS  Google Scholar 

  6. Giles DE, Jarret RB, Roffwarg HP, et al.: Reduced rapid eye movement latency: a predictor of recurrence in depression. Neuropsychopharmacology 1987, 1:33–39.

    Article  PubMed  CAS  Google Scholar 

  7. Hasler G, Drevets WC, Manji HK, et al.: Discovering endophenotypes for major depression. Neuropsychopharmacology 2004, 29:1765–1781.

    Article  PubMed  CAS  Google Scholar 

  8. Gottesman II, Shields J: Genetic theorizing and schizophrenia. Br J Psychiatry 1973, 122:15–36.

    Article  PubMed  CAS  Google Scholar 

  9. Gottesman II, Gould TD: The endophenotype concept in psychiatry: etymology and strategic intentions. Am J Psychiatry 2003, 160:636–645.

    Article  PubMed  Google Scholar 

  10. Tsuang MT, Faraone SV, Lyons MJ: Identification of the phenotype in psychiatric genetics. Eur Arch Psychiatry Clin Neurosci 1993, 243:131–142.

    Article  PubMed  CAS  Google Scholar 

  11. Buysse DJ, Kupfer DJ, Frank E, et al.: Electroencephalographic sleep studies in depressed outpatients treated with interpersonal therapy: II. Longitudinal studies at baseline and recovery. Psychiatry Res 1992, 40:27–40.

    Article  Google Scholar 

  12. Linkowski P, Kerkhofs M, Hauspie R, et al.: EEG sleep patterns in man: a twin study. Electroencephalogr Clin Neurophysiol 1989, 73:279–284.

    Article  PubMed  CAS  Google Scholar 

  13. Ho AP, Gillin JC, Buchsbaum MS, et al.: Brain glucose metabolism during non-rapid eye movement sleep in major depression: a positron emission tomography study. Arch Gen Psychiatry 1996, 53:645–652.

    PubMed  CAS  Google Scholar 

  14. Lauer C, Riemann D, Wiegand M, et al.: From early to late adulthood. Changes in EEG sleep of depressed patients and healthy volunteers. Biol Psychiatry 1991, 29:979–993.

    Article  PubMed  CAS  Google Scholar 

  15. Battaglia M, Strambi LF, Bertella S, et al.: First-cycle REM density in never-depressed subjects with borderline personality disorder. Biol Psychiatry 1999, 45:1056–1058.

    Article  PubMed  CAS  Google Scholar 

  16. Clark CP, Gillin JC, Golshan S, et al.: Polysomnography and depressive symptoms in primary alcoholics with and without a lifetime diagnosis of secondary depression and in patients with primary major depression. J Affect Disord 1999, 55:177–185.

    Article  Google Scholar 

  17. Jindal RD, Thase ME, Fasiczka AL, et al.: Electroencephalographic sleep profiles in single-episode and recurrent unipolar forms of major depression: II. Comparison during remission. Biol Psychiatry 2002, 51:230–236.

    Article  PubMed  Google Scholar 

  18. Clark C, Dupont R, Golshan S, et al.: Preliminary evidence of an association between increased REM density and poor antidepressant response to partial sleep deprivation. J Affect Disord 2000, 59:77–83.

    Article  PubMed  CAS  Google Scholar 

  19. Thase ME, Bysee DJ, Frank E, et al.: Which depressed patients will respond to interpersonal psychotherapy? The role of abnormal EEG sleep profiles. Am J Psychiatry 1997, 154:502–509.

    PubMed  CAS  Google Scholar 

  20. Buysse DJ, Tu XM, Cherry CR, et al.: Pretreatment REM sleep and subjective sleep quality distinguish depressed psychotherapy remitters and nonremitters. Biol Psychiatry 1999, 45:205–213.

    Article  PubMed  CAS  Google Scholar 

  21. Haynes PL, McQuaid JR, Kelsoe J, et al.: Affective state and EEG sleep profile in response to rapid tryptophan depletion in recently recovered nonmedicated depressed individuals. J Affect Disord 2004, 83:253–262.

    Article  PubMed  CAS  Google Scholar 

  22. Hori A: Sleep characteristics in twins. Jpn J Psychiatry Neurol 1986, 40:35–46.

    PubMed  CAS  Google Scholar 

  23. Giles DE, Kupfer DJ, Roffwarg HP, et al.: Polysomnographic parameters in first-degree relatives of unipolar probands. Psychiatry Res 1989, 27:127–136.

    Article  PubMed  CAS  Google Scholar 

  24. Giles DE, Biggs MM, Rush AJ, et al.: Risk factors in families of unipolar depression. I. Psychiatric illness and reduced REM latency. J Affect Disord 1988, 14:51–59.

    Article  PubMed  CAS  Google Scholar 

  25. Giles DE, Etzel BA, Biggs MM: Risk factors in unipolar depression: II. Relation between proband REM latency and cognitions of relatives. Psychiatry Res 1990, 33:39–49.

    Article  PubMed  CAS  Google Scholar 

  26. Janowsky DS, El-Yousef K, Davis J, et al.: A cholinergic-aminergic hypothesis of mania and depression. Lancet 1972, 2:632–635.

    Article  PubMed  CAS  Google Scholar 

  27. Sitaram N, Dube S, Keshavan M, et al.: The association of supersensitive cholinergic REM-induction and affective illness within pedigrees. J Psychiatr Res 1987, 21:487–497.

    Article  PubMed  CAS  Google Scholar 

  28. Goetz RR, Wolk SI, Coplan JD, et al.: Premorbid polysomnographic signs in depressed adolescents: a reanalysis of EEG sleep after longitudinal follow-up in adulthood. Biol Psychiatry 2001, 49:930–942.

    Article  PubMed  CAS  Google Scholar 

  29. Rao U, Dahl RE, Ryan ND, et al.: The relationship between longitudinal clinical course and sleep and cortisol changes in adolescent depression. Biol Psychiatry 1996, 40:474–484.

    Article  PubMed  CAS  Google Scholar 

  30. Fulton MK, Armitage R, Rush AJ: Sleep electroencephalographic coherence abnormalities in individuals at high risk for depression: a pilot study. Biol Psychiatry 2000, 47:618–625.

    Article  PubMed  CAS  Google Scholar 

  31. Lauer CJ, Schreiber W, Holsboer F, et al.: In quest of identifying vulnerability markers for psychiatric disorders by all-night polysomnography. Arch Gen Psychiatry 1995, 52:145–153.

    PubMed  CAS  Google Scholar 

  32. Schreiber W, Lauer CJ, Krumrey K, et al.: Cholinergic REM sleep induction test in subjects at high risk for psychiatric disorders. Biol Psychiatry 1992, 32:79–90.

    Article  PubMed  CAS  Google Scholar 

  33. Modell S, Ising M, Holsboer F, et al.: The Munich Vulnerability Study on affective disorders: stability of polysomnographic findings over time. Biol Psychiatry 2002, 52:430–437.

    Article  PubMed  Google Scholar 

  34. Modell S, Huber J, Holsboer F, et al.: The Munich Vulnerability Study on affective disorders: risk factors for unipolarity versus bipolarity. J Affect Disord 2003, 74:173–184.

    Article  PubMed  Google Scholar 

  35. Modell S, Ising M, Holsboer F, et al.: The Munich Vulnerability Study on affective disorders: premorbid polysomnographic profile of affected high-risk probands. Biol Psychiatry 2005, 58:694–699.

    Article  PubMed  Google Scholar 

  36. Lauer CJ, Modell S, Schreiber W, et al.: Prediction of the development of a first major depressive episode with a rapid eye movement sleep induction test using the cholinergic agonist RS 86. J Clin Psychopharmacol 2004, 24:356–357.

    Article  PubMed  Google Scholar 

  37. Mallick BN, Singh S, Pal D: Role of alpha and beta adrenoceptors in locus coeruleus stimulation-induced reduction in rapid eye movement sleep in freely moving rats. Behav Brain Res 2005, 158:9–21.

    Article  PubMed  CAS  Google Scholar 

  38. Adrien J: Neurobiological bases for the relation between sleep and depression. Sleep Med Rev 2002, 6:341–351.

    PubMed  Google Scholar 

  39. Rasmussen K, Heyn J, Jacobs BL: Activity of serotonin-containing neurons in nucleus centralis superior of freely moving cats. Exp Neurol 1984, 83:302–317.

    PubMed  CAS  Google Scholar 

  40. Gillin JC, Sohn JW, Stahl SM, et al.: Ipsapirone, a 5-HT1A agonist, suppresses REM sleep equally in unmedicated depressed patients and normal controls. Neuropsychopharmacology 1996, 15:109–115.

    Article  PubMed  CAS  Google Scholar 

  41. Yavari P, Vogel GW, Neill DB: Decreased raphe unit activity in a rat model of endogenous depression. Brain Res 1993, 611:31–36.

    Article  PubMed  CAS  Google Scholar 

  42. Alexandre C, Popa D, Fabre V, et al.: Early-life blockade of 5-HT1A receptors normalizes sleep and depression-like behavior in adult knock-out mice lacking the serotonin transporter. J Neurosci 2006, 17:5554–5564.

    Article  CAS  Google Scholar 

  43. Thomas DR, Melotto S, Massagrande M, et al.: SB-656104-A, a novel selective 5-HT7 receptor antagonist, modulates REM sleep in rats. Br J Pharmacol 2003, 139:705–714.

    Article  PubMed  CAS  Google Scholar 

  44. Sitaram N, Moore AM, Gillin JC: Induction and resting of REM sleep rhythm in normal man by arecoline: blockade by scopolamine. Sleep 1978, 1:83–90.

    PubMed  CAS  Google Scholar 

  45. Gillin JC, Sutton L, Ruiz C, et al.: The cholinergic rapid eye movement induction test with arecoline in depression. Arch Gen Psychiatry 1991, 48:264–270.

    PubMed  CAS  Google Scholar 

  46. Riemann D, Hohagen F, Fleckenstein P, et al.: The cholinergic REM-induction-test with RS 86 after scopolamine pretreatment in healthy subjects. Psychiatry Res 1991, 38:247–260.

    Article  PubMed  CAS  Google Scholar 

  47. Numberger JL, Sitaram N, Gershon ES, et al.: A twin study of cholinergic REM induction. Biol Psychiatry 1983, 18:1161–1165.

    Google Scholar 

  48. Numberger JL, Berretini W, Mendelson WB, et al.: Measuring cholinergic sensitivity: arecoline effects in bipolar patients. Biol Psychiatry 1989, 25:610–617.

    Article  Google Scholar 

  49. Gottesman C, Gottesman I: The neurobiological characteristics of rapid eye movement (REM) sleep are candidate endophenotypes of depression, schizophrenia, mental retardation and dementia. Prog Neurobiol 2007, 81:237–250.

    Article  PubMed  Google Scholar 

  50. Franken P, Malafosse A, Tafti N: Genetic determinants of sleep regulation in inbred mice. Sleep 1999, 22:155–169.

    PubMed  CAS  Google Scholar 

  51. Peigneux P, Laurey S, Fuchs S, et al.: Generation of rapid eye movements during paradoxical sleep in humans. Neuroimage 2001, 14:701–708.

    Article  PubMed  CAS  Google Scholar 

  52. Datta S: Avoidance task training potentiates phasic pontinewave density in the rat: a mechanism for sleep-dependent plasticity. J Neurosci 2000, 20:8607–8613.

    PubMed  CAS  Google Scholar 

  53. Marks GA, Shaffery JP, Oksenberg A, et al.: A functional role for REM sleep in brain maturation. Behav Brain Res 1995, 69:1–11.

    Article  PubMed  CAS  Google Scholar 

  54. Vogel GW, Feng PF, Kinney GG: Ontogeny of REM sleep in rats: possible implications for endogenous depression. Physiol Behav 2000, 68:453–461.

    Article  PubMed  CAS  Google Scholar 

  55. Comings DE, Wu S, Rostamkhani M, et al.: Association of the muscarinic cholinergic 2 receptor (CHRM2) gene with major depression in women. Am J Med Genet 2002, 114:527–529.

    Article  PubMed  Google Scholar 

  56. Nievergelt C, Kripke DF, Barrett TB, et al.: Suggestive evidence for association of the circadian genes PERIOD3 and ARNTL with bipolar disorder. Am J Med Genet B Neuropsychiatr Genet 2006, 141:234–241.

    PubMed  Google Scholar 

  57. Taheri S, Mignot E: The genetics of sleep disorders. Lancet Neurol 2002, 1:242–250.

    Article  PubMed  CAS  Google Scholar 

  58. Tafti M, Chollet D, Valatx JL, et al.: Quantitative trait loci approach to the genetics of sleep in recombinant inbred mice. J Sleep Res 1999, 8(Suppl 1):37–43.

    Article  PubMed  Google Scholar 

  59. Terao A, Wisor JP, Peyron C, et al.: Gene expression in the rat brain during sleep deprivation and recovery sleep: an Affymetrix GeneChip Study. Neuroscience 2006, 137:593–605.

    Article  PubMed  CAS  Google Scholar 

  60. Zubenko GS, Hughes HB 3rd, Maher BS, et al.: Genetic linkage of region containing the CREB1 gene to depressive disorders in women from families with recurrent, early-onset, major depression. Am J Med Genet 2002, 114:980–987.

    Article  PubMed  Google Scholar 

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Correspondence to Sieglinde Modell.

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Modell, S., Lauer, C.J. Rapid eye movement (REM) sleep: An endophenotype for depression. Curr Psychiatry Rep 9, 480–485 (2007). https://doi.org/10.1007/s11920-007-0065-z

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