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Pharmacopsychiatry 2013; 46(S 01): S30-S35
DOI: 10.1055/s-0033-1337921
Original Paper
© Georg Thieme Verlag KG Stuttgart · New York

Pathology of Sleep, Hormones and Depression

A. Steiger
1   Department of Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany
,
M. Dresler
1   Department of Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany
,
M. Kluge
1   Department of Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany
2   Department of Psychiatry, University of Leipzig, Leipzig, Germany
,
P. Schüssler
1   Department of Psychiatry, Max Planck Institute of Psychiatry, Munich, Germany
› Author Affiliations
Further Information

Publication History

Publication Date:
18 April 2013 (online)

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Abstract

In patients with depression, characteristic changes of sleep electroencephalogram and nocturnal hormone secretion occur including rapid eye movement (REM) sleep disinhibition, reduced non-REM sleep and impaired sleep continuity. Neuropeptides are common regulators of the sleep electroencephalogram (EEG) and nocturnal hormone secretion and changes in their activity appear to contribute to the aberrances of sleep in affective disorders. A reciprocal interaction of the sleep-promoting growth hormone-releasing hormone (GHRH) and corticotrophin-releasing hormone (CRH), which promotes wakefulness and REM sleep, plays a key role in sleep regulation, at least in male subjects. Also galanin and ghrelin promote sleep in men. Neuropeptide Y is involved in the timing of sleep onset. The effects of peptides of sleep are influenced by the time of administration, age, gender and depression. In healthy subjects and in remitted depressed patients motoric memory learning is consolidated during sleep. This effect is absent in depressed patients who are at least 30 years old, and is probably related to elevated glucocorticoid levels.

Key words

depression - sleep - peptides - memory - motoric learning
 

  • References

  • 1 Steiger A. Neurochemical regulation of sleep. J Psychiatr Res 2007; 41: 537-552
    CrossrefPubMedGoogle Scholar
  • 2 Kupfer DJ. Sleep research in depressive illness: clinical implications – a tasting menu. Biol Psychiatry 1995; 38: 391-403
    CrossrefPubMedGoogle Scholar
  • 3 Bliwise DL. Sleep in normal aging and dementia. Sleep 1993; 16: 40-81
    PubMedGoogle Scholar
  • 4 Ehlers CL, Reed TK, Henriksen SJ. Effects of corticotropin-releasing factor and growth hormone-releasing factor on sleep and activity in rats. Neuroendocrinology 1986; 42: 467-474
    CrossrefPubMedGoogle Scholar
  • 5 Kimura M, Muller-Preuss P, Lu A et al. Conditional corticotropin-releasing hormone overexpression in the mouse forebrain enhances rapid eye movement sleep. Mol Psychiatry 2010; 15: 154-165
    CrossrefPubMedGoogle Scholar
  • 6 Steiger A, Guldner J, Hemmeter U et al. Effects of growth hormone-releasing hormone and somatostatin on sleep EEG and nocturnal hormone secretion in male controls. Neuroendocrinology 1992; 56: 566-573
    CrossrefPubMedGoogle Scholar
  • 7 Holsboer F, von Bardeleben U, Steiger A. Effects of intravenous corticotropin-releasing hormone upon sleep-related growth hormone surge and sleep EEG in man. Neuroendocrinology 1988; 48: 32-38
    CrossrefPubMedGoogle Scholar
  • 8 Ehlers CL, Kupfer DJ. Hypothalamic peptide modulation of EEG sleep in depression: a further application of the S-process hypothesis. Biol Psychiatry 1987; 22: 513-517
    CrossrefPubMedGoogle Scholar
  • 9 Mendelson WB, Slater S, Gold P et al. The effect of growth hormone administration on human sleep: a dose-response study. Biol Psychiatry 1980; 15: 613-618
    PubMedGoogle Scholar
  • 10 Obal J, Krueger JM. GHRH and sleep. Sleep Med Rev 2004; 8: 367-377
    CrossrefPubMedGoogle Scholar
  • 11 Friess E, von Bardeleben U, Wiedemann K et al. Effects of pulsatile cortisol infusion on sleep-EEG and nocturnal growth hormone release in healthy men. J Sleep Res 1994; 3: 73-79
    CrossrefPubMedGoogle Scholar
  • 12 Steiger A, Guldner J, Knisatschek H et al. Effects of an ACTH/MSH(4-9) analog (HOE 427) on the sleep EEG and nocturnal hormonal secretion in humans. Peptides 1991; 12: 1007-1010
    CrossrefPubMedGoogle Scholar
  • 13 Murck H, Antonijevic I, Frieboes RM et al. Galanin has REM-sleep deprivation-like effects on the sleep EEG in healthy young men. J Psychiatr Res 1999; 33: 225-232
    CrossrefPubMedGoogle Scholar
  • 14 Saper CB, Chou TC, Scammell TE. The sleep switch: hypothalamic control of sleep and wakefulness. Trends Neurosci 2001; 24: 726-731
    CrossrefPubMedGoogle Scholar
  • 15 Marshall L, Derad I, Strasburger CJ et al. A determinant factor in the efficacy of GHRH administration in promoting sleep: high peak concentration versus recurrent increasing slopes. Psychoneuroendocrinology 1999; 24: 363-370
    CrossrefPubMedGoogle Scholar
  • 16 Schier T, Guldner J, Colla M et al. Changes in sleep-endocrine activity after growth hormone-releasing hormone depend on time of administration. J Neuroendocrinol 1997; 9: 201-205
    PubMedGoogle Scholar
  • 17 Iovino M, Monteleone P, Steardo L. Repetitive growth hormone-releasing hormone administration restores the attenuated growth hormone (GH) response to GH-releasing hormone testing in normal aging. J Clin Endocrinol Metab 1989; 69: 910-913
    CrossrefPubMedGoogle Scholar
  • 18 Guldner J, Schier T, Friess E et al. Reduced efficacy of growth hormone-releasing hormone in modulating sleep endocrine activity in the elderly. Neurobiol Aging 1997; 18: 491-495
    CrossrefPubMedGoogle Scholar
  • 19 Antonijevic IA, Murck H, Frieboes RM et al. Sexually dimorphic effects of GHRH on sleep-endocrine activity in patients with depression and normal controls – part I: the sleep EEG. Sleep Res Online 2000; 3: 5-13
    PubMedGoogle Scholar
  • 20 Antonijevic IA, Murck H, Frieboes RM et al. Sexually dimorphic effects of GHRH on sleep-endocrine activity in patients with depression and normal controls – part II: hormone secretion. Sleep Res Online 2000; 3: 15-21
    PubMedGoogle Scholar
  • 21 Mathias S, Held K, Ising M et al. Systemic growth hormone-releasing hormone (GHRH) impairs sleep in healthy young women. Psychoneuroendocrinology 2007; 32: 1021-1027
    CrossrefPubMedGoogle Scholar
  • 22 Frieboes RM, Murck H, Schier T et al. Somatostatin impairs sleep in elderly human subjects. Neuropsychopharmacology 1997; 16: 339-345
    CrossrefPubMedGoogle Scholar
  • 23 Ziegenbein M, Held K, Kuenzel HE et al. The somatostatin analogue octreotide impairs sleep and decreases EEG sigma power in young male subjects. Neuropsychopharmacology 2004; 29: 146-151
    CrossrefPubMedGoogle Scholar
  • 24 Schüssler P, Kluge M, Dresler M et al. Sleep-impairing effect of intravenous corticotropin-releasing hormone on sleep EEG in young healthy women. Exp Clin Endocrinol Diabetes 2009; 117: 664
    PubMedGoogle Scholar
  • 25 Held K, Künzel H, Ising M et al. Treatment with the CRH1-receptor-antagonist R121919 improves sleep-EEG in patients with depression. J Psychiatr Res 2004; 38: 129-136
    CrossrefPubMedGoogle Scholar
  • 26 Ehlers CL, Somes C, Lopez A et al. Electrophysiological actions of neuropeptide Y and its analogs: new measures for anxiolytic therapy?. Neuropsychopharmacology 1997; 17: 34-43
    CrossrefPubMedGoogle Scholar
  • 27 Ehlers CL, Somes C, Seifritz E et al. CRF/NPY interactions: a potential role in sleep dysregulation in depression and anxiety. Depress Anxiety 1997; 6: 1-9
    CrossrefPubMedGoogle Scholar
  • 28 Held K, Antonijevic I, Murck H et al. Neuropeptide Y (NPY) shortens sleep latency but does not suppress ACTH and cortisol in depressed patients and normal controls. Psychoneuroendocrinology 2006; 31: 100-107
    CrossrefPubMedGoogle Scholar
  • 29 Hillman JB, Tong J, Tschop M. Ghrelin biology and its role in weight-related disorders. Discov Med 2011; 11: 521-528
    PubMedGoogle Scholar
  • 30 Weikel JC, Wichniak A, Ising M et al. Ghrelin promotes slow-wave sleep in humans. Am J Physiol – Endocrinol Metab 2003; 284: E407-E415
    PubMedGoogle Scholar
  • 31 Kluge M, Schüssler P, Zuber V et al. Ghrelin administered in the early morning increases secretion of cortisol and growth hormone without affecting sleep. Psychoneuroendocrinology 2007; 32: 287-292
    CrossrefPubMedGoogle Scholar
  • 32 Kluge M, Gazea M, Schüssler P et al. Ghrelin increases slow wave sleep and stage 2 sleep and decreases stage 1 sleep and REM sleep in elderly men but does not affect sleep in elderly women. Psychoneuroendocrinology 2010; 35: 297-304
    CrossrefPubMedGoogle Scholar
  • 33 Kluge M, Schüssler P, Zuber V et al. Ghrelin enhances the nocturnal secretion of cortisol and growth hormone in young females without influencing sleep. Psychoneuroendocrinology 2007; 32: 1079-1085
    CrossrefPubMedGoogle Scholar
  • 34 Kluge M, Schüssler P, Dresler M et al. Effects of ghrelin on psychopathology, sleep and secretion of cortisol and growth hormone in patients with major depression. J Psychiatr Res 2011; 45: 421-426
    CrossrefPubMedGoogle Scholar
  • 35 Kluge M, Schüssler P, Bleninger P et al. Ghrelin alone or co-administered with GHRH or CRH increases non-REM sleep and decreases REM sleep in young males. Psychoneuroendocrinology 2008; 33: 497-506
    CrossrefPubMedGoogle Scholar
  • 36 Murck H, Held K, Ziegenbein M et al. Intravenous administration of the neuropeptide galanin has fast antidepressant efficacy and affects the sleep EEG. Psychoneuroendocrinology 2004; 29: 1205-1211
    CrossrefPubMedGoogle Scholar
  • 37 Dresler M, Kluge M, Genzel L et al. Impaired off-line memory consolidation in depression. Eur Neuropsychopharmacol 2010; 20: 553-561
    CrossrefPubMedGoogle Scholar
  • 38 Genzel L, Ali E, Dresler M et al. Sleep-dependent memory consolidation of a new task is inhibited in psychiatric patients. J Psychiatr Res 2011; 45: 555-560
    CrossrefPubMedGoogle Scholar
  • 39 Steiger A, von Bardeleben U, Herth T et al. Sleep EEG and nocturnal secretion of cortisol and growth hormone in male patients with endogenous depression before treatment and after recovery. J Affect Disord 1989; 16: 189-195
    CrossrefPubMedGoogle Scholar
  • 40 Dresler M, Kluge M, Pawlowski M et al. A double dissociation of memory impairments in major depression. J Psychiatr Res 2011; 45: 1593-1599
    CrossrefPubMedGoogle Scholar
  • 41 Plihal W, Born J. Effects of early and late nocturnal sleep on declarative and procedural memory. J Cogn Neurosci 1997; 9: 534-547
    CrossrefPubMedGoogle Scholar
  • 42 Rasch B, Pommer J, Diekelmann S et al. Pharmacological REM sleep suppression paradoxically improves rather than impairs skill memory. Nat Neurosci 2009; 12: 396-397
    CrossrefPubMedGoogle Scholar
  • 43 Genzel L, Dresler M, Wehrle R et al. Slow wave sleep and REM sleep awakenings do not affect sleep dependent memory consolidation. Sleep 2009; 32: 302-310
    PubMedGoogle Scholar
  • 44 Genzel L, Kiefer T, Renner L et al. Sex and modulatory menstrual cycle effects on sleep related memory consolidation. Psychoneuroendocrinology 2012; 37: 987-998
    CrossrefPubMedGoogle Scholar
  • 45 Dresler M, Genzel L, Kluge M et al. Off-line memory consolidation impairments in multiple sclerosis patients receiving high-dose corticosteroid treatment mirror consolidation impairments in depression. Psychoneuroendocrinology 2010; 35: 1194-1202
    CrossrefPubMedGoogle Scholar
  • 46 Borbély AA. A two-process model of sleep regulation. Hum Neurobiol 1982; 1: 195-204
    PubMedGoogle Scholar
  • 47 Borbély AA, Wirz-Justice A. Sleep, sleep deprivation and depression: A hypothesis derived from a model of sleep regulation. Hum Neurobiol 1982; 1: 205-210
    PubMedGoogle Scholar