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Pharmacopsychiatry 2012; 45(05): 167-176
DOI: 10.1055/s-0031-1299721
Review
© Georg Thieme Verlag KG Stuttgart · New York

REM Sleep Instability – A New Pathway for Insomnia?

D. Riemann
1   Department of Psychiatry and Psychotherapy, Freiburg University Medical Center, Freiburg, Germany
,
K. Spiegelhalder
1   Department of Psychiatry and Psychotherapy, Freiburg University Medical Center, Freiburg, Germany
,
C. Nissen
1   Department of Psychiatry and Psychotherapy, Freiburg University Medical Center, Freiburg, Germany
,
V. Hirscher
1   Department of Psychiatry and Psychotherapy, Freiburg University Medical Center, Freiburg, Germany
,
C. Baglioni
1   Department of Psychiatry and Psychotherapy, Freiburg University Medical Center, Freiburg, Germany
,
B. Feige
1   Department of Psychiatry and Psychotherapy, Freiburg University Medical Center, Freiburg, Germany
› Author Affiliations
Further Information

Publication History

received 11 October 2011
revised 01 December 2011

accepted 12 December 2011

Publication Date:
30 January 2012 (online)

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Abstract

Chronic insomnia afflicts approximately 10% of the adult population and is associated with daytime impairments and an elevated risk for developing somatic and mental disorders. Current pathophysiological models propose a persistent hyperarousal on the cognitive, emotional and physiological levels. However, the marked discrepancy between minor objective alterations in standard parameters of sleep continuity and the profound subjective impairment in patients with insomnia is unresolved. We propose that “instability” of REM sleep contributes to the experience of disrupted and non-restorative sleep and to the explanation of this discrepancy. This concept is based on evidence showing increased micro- and macro-arousals during REM sleep in insomnia patients. As REM sleep represents the most highly aroused brain state during sleep it seems particularly prone to fragmentation in individuals with persistent hyperarousal. The continuity hypothesis of dream production suggests that pre-sleep concerns of patients with insomnia, i. e., worries about poor sleep and its consequences, dominate their dream content. Enhanced arousal during REM sleep may render these wake-like cognitions more accessible to conscious perception, memory storage and morning recall, resulting in the experience of disrupted and non-restorative sleep. Furthermore, chronic fragmentation of REM sleep might lead to dysfunction in a ventral emotional neural network, including limbic and paralimbic areas that are specifically activated during REM sleep. This dysfunction, along with attenuated functioning in a dorsal executive neural network, including frontal and prefrontal areas, might contribute to emotional and cognitive alterations and an elevated risk of developing depression.

Key words

insomnia - hyperarousal - REM sleep instability
 

  • References

  • 1 Perlis ML, Gehrman P, Terzano M et al. EEG in patients with primary insomnia. In: Buysse D, Sateia M. editors. Insomnia: diagnosis and treatment. London: Taylor & Francis; 2010. 50-64
    CrossrefGoogle Scholar
  • 2 ICSD-2 . International classification of sleep disorders. 2nd edition. In: AASM (American Academy of Sleep Medicine), editor. Westchester, IL: 2005
    Google Scholar
  • 3 Kushida CA, Littner M, Morgenthaler T et al. Practice parameters for the indications for polysomnography and related procedures: an update for 2005. Sleep 2005; 28: 499-521
    PubMedGoogle Scholar
  • 4 Riemann D, Perlis ML. The treatments of chronic insomnia: a review of benzodiazepine receptor agonists and psychological and behavioural therapies. Sleep Med Rev 2009; 13: 205-214
    CrossrefPubMedGoogle Scholar
  • 5 Vgontzas AN, Bixler EO, Lin HM et al. Chronic insomnia is associated with nyctohemeral activation of the hypothalamic-pituitary-adrenal axis: clinical implications. J Clin Endocrinol Metab 2001; 86: 3787-3794
    CrossrefPubMedGoogle Scholar
  • 6 Burgos I, Richter L, Klein T et al. Increased nocturnal Interleukin-6 excretion in patients with primary insomnia: a pilot study. Brain Behav Immun 2006; 20: 246-253
    Google Scholar
  • 7 Nofzinger EA, Buysse DJ, Germain A et al. Functional neuroimaging evidence for hyperarousal in insomnia. Am J Psychiatry 2004; 161: 2126-2129
    Google Scholar
  • 8 Nofzinger EA, Nissen C, Germain A et al. Regional cerebral metabolic correlates of WASO during NREM sleep in insomnia. J Clin Sleep Med 2006; 2: 316-322
    PubMedGoogle Scholar
  • 9 Riemann D, Voderholzer U, Spiegelhalder K et al. Chronic insomnia and MRI-measured hippocampal volumes: a pilot study. Sleep 2007; 30: 955-958
    Google Scholar
  • 10 Deuschle M, Schredl M, Schilling C et al. Association between a serotonin transporter length polymorphism and primary insomnia. Sleep 2010; 33: 343-347
    PubMedGoogle Scholar
  • 11 Bonnet M, Arand DL. Hyperarousal and insomnia: state of the science. Sleep Med Rev 2010; 14: 9-15
    CrossrefPubMedGoogle Scholar
  • 12 Riemann D, Spiegelhalder K, Feige B et al. The hyperarousal model of insomnia: A review of the concept and its evidence. Sleep Med Rev 2010; 14: 19-31
    CrossrefPubMedGoogle Scholar
  • 13 Krystal AD, Walsh JK, Laska E et al. Sustained efficacy of eszopiclone over 6 months of nightly treatment: results of a randomized, double-blind, placebo-controlled study in adults with chronic insomnia. Sleep 2003; 26: 793-799
    Google Scholar
  • 14 Roth T, Walsh JK, Krystal A et al. An evaluation of the efficacy and safety of eszopiclone over 12 months in patients with chronic insomnia. Sleep Med 2005; 6: 487-495
    CrossrefPubMedGoogle Scholar
  • 15 Kripke DF, Simons RN, Garfinkel L et al. Short and long sleep and sleeping pills; is increased mortality associated?. Arch Gen Psychiat 1979; 36: 103-116
    CrossrefPubMedGoogle Scholar
  • 16 Kripke DF, Klauber MR, Wingard DL et al. Mortality hazard associated with prescription hypnotics. Biol Psychiat 1998; 43: 687-93
    CrossrefPubMedGoogle Scholar
  • 17 Kripke DF. Chronic hypnotic use: deadly risks, doubtful benefit. Sleep Med Rev 2000; 4: 5-20
    Google Scholar
  • 18 Morin CM, Culbert JP, Schwartz SM. Non-pharmacological interventions for insomnia: A meta-analysis of treatment efficacy. Am J Psychiatry 1994; 151: 1172-1180
    Google Scholar
  • 19 Murtagh DR, Greenwood KM. Identifying effective psychological treatments for insomnia: a meta-analysis. J Consult Clin Psychol 1995; 63: 79-89
    Google Scholar
  • 20 Morin CM, Vallieres A, Guay B et al. Cognitive behavioral therapy, singly and combined with medication, for persistent insomnia. JAMA 2009; 301: 2005-2015
    CrossrefPubMedGoogle Scholar
  • 21 NIH . National Institutes of health state of the science conference statement. Manifestations and management of chronic insomnia in adults, June 13-15, 2005. Sleep 2005; 28: 1049-1057
    PubMedGoogle Scholar
  • 22 Riemann D, Spiegelhalder K, Espie C et al. Chronic insomnia: clinical and research challenges – an agenda. Pharmacopsychiatry 2011; 44: 1-14
    Article in Thieme ConnectPubMedGoogle Scholar
  • 23 Holtzheimer PE, Mayberg HS. Stuck in a rut: rethinking depression and its treatment. TINS 2011; 34: 1-9
    PubMedGoogle Scholar
  • 24 Feige B, Al-Shajlawi A, Nissen C et al. Does REM sleep contribute to subjective wake time in primary insomnia? A comparison of poly­somnographic and subjective sleep in 100 patients. J Sleep Res 2008; 17: 180-190
    CrossrefPubMedGoogle Scholar
  • 25 ASDA report . EEG arousals: scoring rules and examples. Sleep 1992; 15: 173-184
    PubMedGoogle Scholar
  • 26 Maquet P, Péters JM, Aerts J et al. Functional neuroanatomy of human rapid-eye-movement sleep and dreaming. Nature 1996; 383: 163-166
    CrossrefPubMedGoogle Scholar
  • 27 Aserinsky E, Kleitman N. Regularly occurring periods of eye motility and concomitant phenomena during sleep. Science 1953; 118: 273-274
    CrossrefPubMedGoogle Scholar
  • 28 Jouvet M. The paradoxical phase of sleep. Int J Neurol 1965; 5: 131-150
    PubMedGoogle Scholar
  • 29 Hobson JA, McCarley RW, Wyzinski PW. Sleep cycle oscillation: reciprocal discharge by two brainstem neuronal groups. Science 1975; 189: 55-58
    CrossrefPubMedGoogle Scholar
  • 30 Hobson JA, Lydic R, Baghdoyan HA. Evolving concepts of sleep cycle generation: from brain centers to neuronal populations. Behav Brain Sci 1986; 9: 371-448
    CrossrefPubMedGoogle Scholar
  • 31 Baumann CR, Bassetti C. Hypocretins (orexins) and sleep-wake disorders. Lancet Neurol 2005; 4: 673-682
    CrossrefPubMedGoogle Scholar
  • 32 McCarley RW. Neurobiology of REM and NREM sleep. Sleep Med 2007; 8: 302-330
    CrossrefPubMedGoogle Scholar
  • 33 Saper CB, Scammell TE, Lu J. Hypothalamic regulation of sleep and circadian rhythms. Nature 2005; 437: 1257-1263
    Google Scholar
  • 34 Mieda M, Hasagawa E, KIsanuki YY et al. Differential role of orexin receptor-1 and -2 in the regulation of non-REM and REM sleep. J Neurosci 2011; 27: 6518-6526
    PubMedGoogle Scholar
  • 35 Lu J, Sherman D, Devor M et al. A putative flip-flop switch for control of REM sleep. Nature 2006; 441: 589-594
    CrossrefPubMedGoogle Scholar
  • 36 Luppi PH, Clement O, Sapin E et al. The neuronal network responsible for paradoxical sleep and its dysfunctions causing narcolepsy and rapid eye movement (REM) sleep behavior disorder. Sleep Med Rev 2011; 15: 153-163
    CrossrefPubMedGoogle Scholar
  • 37 Haas H, Panula P. The role of histamine and the tuberomamillary nucleus in the nervous system. Nature Rev. Neurosci 2003; 4: 121-130
    PubMed
  • 38 Thakkar MM. Histamine in the regulation of wakefulness. Sleep Med Rev 2011; 15: 65-74
    CrossrefPubMedGoogle Scholar
  • 39 Eriksson KS, Sergeeva OA, Haas HL et al. Orexins/hypocretins and aminergic systems. Acta Physiol 2010; 198: 263-275
    CrossrefPubMedGoogle Scholar
  • 40 Gao XB, Wang AH. Experience-dependent plasticity in hypocretin/orexin neurones: re-setting arousal threshold. Acta Physiol 2010; 198: 251-262
    CrossrefPubMedGoogle Scholar
  • 41 Mäkela KA, Wigren HK, Zant JC et al. Characterization of sleep-wake patterns in a novel transgenic mouse line overexpressing human prepro-orexin/hypocretin. Acta Physiol 2010; 198: 237-249
    CrossrefPubMedGoogle Scholar
  • 42 Baumann CR, Werth E, Stocker R et al. Sleep-wake disturbances 6 months after traumatic brain injury: a prospective study. Brain 2007; 130: 1873-1883
    CrossrefPubMedGoogle Scholar
  • 43 Koenigs M, Holliday J, Solomon J et al. Left dorsomedial frontal brain damage is associated with insomnia. J Neurosci 2010; 30: 16041-16043
    CrossrefPubMedGoogle Scholar
  • 44 Rutgers DR, Toulgoat F, Cazejust J et al. White matter abnormalities in mild traumatic brain injury: a diffusion tensor imaging study. AJNR 2008; 29: 514-519
    CrossrefPubMedGoogle Scholar
  • 45 Jacobson KA, Gao ZG. Adenosine receptors as therapeutic targets. Nature Rev 2006; 5: 247-264
    CrossrefPubMedGoogle Scholar
  • 46 Retey JV, Adam M, Honegger E et al. A functional genetic variation of adenosine deaminase affects the duration and intensity of deep sleep in humans. PNA 2005; 102: 15676-15681
    PubMedGoogle Scholar
  • 47 Pawlyk AC, Morrison AR, Ross RJ et al. Stress-induced changes in sleep in rodents: models and mechanisms. Neurosci Biobehav Rev 2008; 32: 99-117
    CrossrefPubMedGoogle Scholar
  • 48 Revel FG, Gottowik J, Gatti S et al. Rodent models of insomnia: a review of experimental procedures that induce sleep disturbances. Neurosci Biobehav Rev 2009; 33: 874-899
    CrossrefPubMedGoogle Scholar
  • 49 Cano G, Mochizuki T, Saper CB. Neural circuitry of stress-induced insomnia in rats. J Neurosci 2008; 28: 10167-10184
    CrossrefPubMedGoogle Scholar
  • 50 Fenzl T, Touma C, Romanowski CP et al. Sleep disturbances in highly stress reactive mice: Modeling endophenotypes of major depression. BMC Neuroscience 2011; 12: 1-12
    CrossrefPubMedGoogle Scholar
  • 51 Kimura M, Müller-Preuss P, Lu A et al. Conditional corticotrophin-releasing hormone overexpression in the mouse forebrain enhances rapid eye movement sleep. Mol Psychiatry 2010; 15: 154-165
    CrossrefPubMedGoogle Scholar
  • 52 Espie CA, Broomfield NM, MacMahon K et al. The attention-intention-effort pathway in the development of psychophysiologic insomnia: a theoretical review. Sleep Med Rev 2006; 10: 215-245
    CrossrefPubMedGoogle Scholar
  • 53 Perlis Giles ML, Mendelson DE, Bootzin WB. et al. insomnia: the behavioural model and a neurocognitive perspective. J Sleep Res 1997; 6: 179-188
    CrossrefPubMedGoogle Scholar
  • 54 Perlis ML, Pigeon WR, Drummond SP. The neurobiology of insomnia. In: Gilman S. editor. Neurobiology of Disease. Burlington, MA: Elsevier; 2006. 735-744
    Google Scholar
  • 55 Stepanski E, Zorick F, Roehrs T et al. Effects of sleep deprivation on daytime sleepiness in primary insomnia. Sleep 2000; 23: 1-5
    PubMedGoogle Scholar
  • 56 Achermann P, Borbely AA. Sleep homestasis and models of sleep regulation. In: Kryger MH, Roth T, Dement WC. editors. Principles and Practice of Sleep Medicine. 5th edition. St. Louis: Elsevier Saunders; 2011. 431-444
    CrossrefGoogle Scholar
  • 57 Lopez J, Roffwarg HP, Dreher A et al. Rapid eye movement sleep deprivation decreases long-term potentiation stability and affects some glutamatergic signalling processing proteins during hippocampal development. Neuroscience 2008; 153: 44-53
    CrossrefPubMedGoogle Scholar
  • 58 Perry JC, Bergamasci CT, Campos RR et al. Sympapthetic and angiotensinergic responses mediated by paradoxical sleep loss in rats. J Renin Angiotensin Aldosterone Syst. 2011 in press
    PubMedGoogle Scholar
  • 59 Khadrawy YA, Nour NA, Aboul Ezz HS. Effect of oxidative stress induced by paradoxical sleep deprivation on the activities of Na+, K+-ATPase and acetylcholinesterase in the cortex and hippocampus of the rat. Transl Res 2011; 157: 100-107
    CrossrefPubMedGoogle Scholar
  • 60 Desseilles M, Vu TD, Laureys S et al. A prominent role for amygdaloid complexes in the variability in heart rate (VHR) during rapid eye movement (REM) sleep relative to wakefulness. Neuroimage 2006; 32: 1008-1015
    CrossrefPubMedGoogle Scholar
  • 61 Nissen C, Klöpfer C, Feige B et al. Sleep-related memory consolidation in primary insomnia. J Sleep Res 2011; 20: 129-136
    CrossrefPubMedGoogle Scholar
  • 62 Spiegelhalder K, Fuchs L, Ladwig J et al. Heart rate and heart rate variability in subjectively reported insomnia. J Sleep Res 2011; 20: 137-145
    CrossrefPubMedGoogle Scholar
  • 63 Mallick BN, Singh A. REM sleep loss increases brain excitability: Role of noradrenalin and its mechanism of action. Sleep Med Rev 2011; 15: 165-178
    CrossrefPubMedGoogle Scholar
  • 64 Riemann D, Berger M, Voderholzer U. Sleep and depression – results from psychobiological studies: an overview. Biol Psychol 2001; 57: 67-103
    CrossrefPubMedGoogle Scholar
  • 65 Baglioni C, Battagliese G, Feige B et al. Insomnia as a predictor of depression: A meta-analytic evaluation of longitudinal epidemiological studies. J Affect Disord 2011; 135: 10-19
    CrossrefPubMedGoogle Scholar
  • 66 Dement W, Kleitman N. Cyclic variations in EEG during sleep and their relations to eye movements, body motility and dreaming. Electroenceph Clin Neurophysiol 1957; 9: 673-690
    CrossrefPubMedGoogle Scholar
  • 67 Nielsen T, Stenstrom P. What are the memory sources of dreaming?. Nature 2005; 437: 1286-1289
    CrossrefPubMedGoogle Scholar
  • 68 Schredl M. Dreams in patients with sleep disorders. Sleep Med Rev 2009; 13: 215-221
    CrossrefPubMedGoogle Scholar
  • 69 Harvey AG. A cognitive model of insomnia. Behav Res Ther 2002; 40: 869-893
    CrossrefPubMedGoogle Scholar
  • 70 Zoccola PM, Dickerson SS, Lam S. Rumination predicts longer sleep onset latency after an acute psychosocial stressor. Psychosom Med 2009; 71: 771-775
    CrossrefPubMedGoogle Scholar
  • 71 Carney CE, Harris AL, Moss TG et al. Distinguishing rumination from worry in clinical insomnia. Behav Res Ther 2010; 48: 540-546
    CrossrefPubMedGoogle Scholar
  • 72 Harvey AG. Pre-sleep cognitive activity: a comparison of sleep-onset insomniacs and good sleepers. Brit J Clin Psychol 2000; 39: 275-286
    CrossrefPubMedGoogle Scholar
  • 73 Wicklow A, Espie CA. Intrusive thoughts and their relationship to actigraphic measurement of sleep: towards a cognitive model of insomnia. Behav Res Therapy 2000; 38: 679-693
    CrossrefPubMedGoogle Scholar
  • 74 Carney CE, Edinger JD, Meyer B et al. Symptom-focused rumination and sleep disturbance. Behav Sleep Med 2006; 4: 228-241
    CrossrefPubMedGoogle Scholar
  • 75 Dresler M, Koch SP, Wehrle R et al. Dreamed movement elicits activation in the sensorimotor cortex. Curr Biol 2011; 21: 1833-1837
    CrossrefPubMedGoogle Scholar
  • 76 Diekelmann S, Born J. The memory of sleep. Nature Rev Neurosci 2010; 11: 114-126
    PubMedGoogle Scholar
  • 77 Lewis PA, Durrant SJ. Overlapping memory replay during sleep builds cognitive schemata. Trends Cogn Sci 2011; 15: 345-35
    PubMedGoogle Scholar
  • 78 Nir Y, Tononi G. Dreaming and the brain: from phenomenology to neurophysiology. Trends Cogn. Sci 2010; 14: 88-100
    CrossrefPubMedGoogle Scholar
  • 79 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
  • 80 Hornung OP, Regen F, Danker-Hopfe H et al. The relationship between REM sleep and memory consolidation in old age and effects of cholinergic medication. Biol Psychiatry 2007; 61: 750-757
    CrossrefPubMedGoogle Scholar
  • 81 Rasch B, Pommer J, Diekelmann S et al. Pharmacological REM sleep suppression paradoxically improves rather than impairs skills memory. Nat Neurosci 2009; 12: 396-397
    CrossrefPubMedGoogle Scholar
  • 82 Saxvig IW, Lundervold AJ, Gronli J et al. The effect of a REM sleep deprivation procedure on different aspects of memory function in humans. Psychophysiology 2008; 45: 309-317
    CrossrefPubMedGoogle Scholar
  • 83 Nissen C, Kloepfer C, Nofzinger EA et al. Impaired sleep-related memory consolidation in primary insomnia – a pilot study. Sleep 2006; 29: 1068-1073
    Google Scholar
  • 84 Walker MP. The role of sleep in cognition and emotion. Ann NY Acad Sci 2009; 1156: 168-197
    CrossrefPubMedGoogle Scholar
  • 85 Wagner U, Gais S, Born J. Emotional memory formation is enhanced across sleep intervals with high amounts of rapid eye movement sleep. Learn Mem 2001; 8: 112-119
    CrossrefPubMedGoogle Scholar
  • 86 Buzsaki G. The hippocampo-neocortical dialogue. Cerebral Cortex 1996; 6: 81-92
    CrossrefPubMedGoogle Scholar
  • 87 Mendelson WB. Hypnotic medications: mechanisms of action and pharmacologic effects. In: Kryger MH, Roth T, Dement WC. editors. Principles and practice of sleep medicine. 5th Edition. St. Louis: Elsevier Saunders; 2011. p 483-491
    CrossrefGoogle Scholar
  • 88 Borbély AA, Mattmann P, Loepfe M et al. Effect of benzodiazepine hypnotics on all-night sleep EEG spectra. Hum Neurobiol 1985; 4: 189-194
    PubMedGoogle Scholar
  • 89 Walsh JK, Schweitzer PK. Ten-year trends in the pharmacological treatment of insomnia. Sleep 1999; 22: 371-375
    PubMedGoogle Scholar
  • 90 Walsh JK. Drugs used to treat insomnia in 2002: regulatory-based rather than evidence-based medicine. Sleep 2004; 27: 1441
    PubMedGoogle Scholar
  • 91 Riemann D, Voderholzer U, Cohrs S et al. Trimipramine in primary insomnia: Results of a polysomnographic double-blind controlled study. Pharmacopsychiatry 2002; 35: 165-174
    Google Scholar
  • 92 Krystal AD, Durrence H, Scharf M et al. Efficacy and safety of doxepin 1 mg and 3 mg in a 12-week sleep laboratory and outpatient trial of elderly subjects with chronic primary insomnia. Sleep 2010; 33: 1553-1561
    PubMedGoogle Scholar
  • 93 Scharf MB, Sachais BA. Sleep laboratory evaluation of the effect of trazodone in depressed insomniacs. Int J Clin Psychiat 1990; 51: 13-17
    PubMedGoogle Scholar
  • 94 Schmid DA, Wichniak A, Uhr M et al. Changes of sleep architecture, spectral composition of sleep EEG, the nocturnal secretion of cortisol, ACTH, GH, prolactin, melatonin, ghrelin, and leptin, and the DEX-CRH test in depressed patients during treatment with mirtazapine. Neuropsychopharmacology 2006; 31: 832-844
    CrossrefPubMedGoogle Scholar
  • 95 Wiegand M, Berger M, Zulley J et al. The effect of trimipramine on sleep in patients with major depressive disorder. Pharmacopsychiatry 1986; 19: 198-199
    Article in Thieme ConnectPubMedGoogle Scholar
  • 96 Wolf R, Dykierek P, Gattaz WF et al. Differential effects of trimipramine and fluoxetine on sleep in geriatric depression. Pharmacopsychiatry 2001; 34: 60-65
    Article in Thieme ConnectPubMedGoogle Scholar
  • 97 Hohagen F, Fritsch-Montero R, Weiss E et al. Treatment of primary insomnia with trimipramine: an alternative to benzodiazepine hypnotics?. Eur Arch Psychiatry Clin Neurosci 1994; 244: 65-72
    CrossrefPubMedGoogle Scholar
  • 98 Schredl M, Berger M, Riemann D. The effect of trimipramine on dream recall and dream emotions in depressive outpatients. Psychiat Res 2009; 167: 279-286
    CrossrefPubMedGoogle Scholar
  • 99 Wiegand M, Galanakis P, Schreiner R. Nefazodone in primary insomnia: an open pilot study. Prog Neuropsychopharmacol Biol Psychiat 2004; 28: 1071-1078
    CrossrefPubMedGoogle Scholar
  • 100 Winokur A, Sateia MJ, Hayes JB et al. Acute effects of mirtazapine on sleep continuity and sleep architecture in depressed patients: a pilot study. Biol Psychiat 2000; 48: 75-78
    CrossrefPubMedGoogle Scholar
  • 101 Brisbare-Roch C, Dingemanse J, Koberstein R et al. Promotion of sleep by targeting the orexin system in rats, dogs and humans. Nature Med 2007; 13: 150-155
    CrossrefPubMedGoogle Scholar
  • 102 Hoever P, de Haas S, Winkler J et al. Orexin receptor antagonism, a new sleep-promoting paradigm: an ascending single-dose study with almorexant. Clin Pharmacol Ther 2010; 87: 593-600
    CrossrefPubMedGoogle Scholar
  • 103 Baier PC, Hallschmid M, Seeck-Hirschner M et al. Effects of intranasal hypocretin-1 (orexin A) on sleep in narcolepsy with cataplexy. Sleep Med Oct 28 2011; [Epub ahead of print]
    PubMedGoogle Scholar
  • 104 Cervena K, Dauvilliers Y, Espa F et al. Effect of cognitive behavioural therapy for insomnia on sleep architecture and sleep EEG power spectra in psychophysiological insomnia. J Sleep Res 2004; 13: 385-393
    CrossrefPubMedGoogle Scholar
  • 105 Morin CM, Bastien C, Guay B et al. Randomized clinical trial of supervised tapering and cognitive behaviour therapy to facilitate benzodiazepine discontinuation in older adults with chronic insomnia. Am J Psychiatry 2004; 161: 332-342
    CrossrefPubMedGoogle Scholar
  • 106 Zavesicka L, Brunovsky M, Matousek M et al. Discontinuation of hypnotics during cognitive behavioural therapy for insomnia. BMC Psychiatry 2008; 8: 80
    CrossrefPubMedGoogle Scholar
  • 107 Baglioni C, Spiegelhalder K, Lombardo C et al. Sleep and emotions: A focus on insomnia. Sleep Med Rev 2010; 14: 227-238
    CrossrefPubMedGoogle Scholar
  • 108 Espie CA. Insomnia: conceptual issues in the development, persistence and treatment of sleep disorders in adults. Annu Rev Psychol 2002; 53: 215-243
    CrossrefPubMedGoogle Scholar
  • 109 Levitt H, Wood A, Moul DE et al. A pilot study of subjective daytime alertness and mood in primary insomnia participants using ecological momentary assessment. Behav Sleep Med 2004; 2: 113-131
    CrossrefPubMedGoogle Scholar
  • 110 Scott BA, Judge TA. Insomnia, emotions, and job satisfaction: a multilevel study. J Manage 2006; 32: 622-645
    CrossrefPubMedGoogle Scholar
  • 111 Buysse DJ, Thompson W, Scott J et al. Daytime symptoms in primary insomnia: a prospective analysis using ecological momentary assessment. Sleep Med 2007; 8: 198-208
    CrossrefPubMedGoogle Scholar
  • 112 McCrae CS, McNamara JP, Rowe MA et al. Sleep and affect in older adults: using multilevel modeling to examine daily associations. J Sleep Res 2008; 17: 42-53
    CrossrefPubMedGoogle Scholar
  • 113 Franzen PL, Siegle GJ, Buysse DJ. Relationships between affect, vigilance, and sleepiness following sleep deprivation. J Sleep Res 2008; 17: 34-41
    CrossrefPubMedGoogle Scholar
  • 114 Franzen PL, Buysse DJ, Dahl RE et al. Sleep deprivation alters pupillary reactivity to emotional stimuli in healthy young adults. Biol Psychol 2009; 80: 300-305
    CrossrefPubMedGoogle Scholar
  • 115 Yoo SS, Gujar N, Hu P et al. The human emotional brain without sleep – a prefrontal amygdala disconnet. Curr Biol 2007; 17: R877-R878
    CrossrefPubMedGoogle Scholar
  • 116 Wagner U, Fischer S, Born J. Changes in emotional responses to aversive pictures across periods rich in slow-wave sleep versus rapid eye movement sleep. Psychosom Med 2002; 64: 627-634
    CrossrefPubMedGoogle Scholar
  • 117 Lara-Carrasco J, Nielsen TA, Solomonova E et al. Overnight emtional adaptation to negative stimuli is altered by REM sleep deprivation and is correlated with intervening dream emotions. J Sleep Res 2009; 18: 178-187
    CrossrefPubMedGoogle Scholar
  • 118 Baglioni C, Lombardo C, Bux E et al. Psychophysiological reactivity to sleep-related stimuli in primary insomnia. Behav Res Ther 2010; 48: 467-475
    CrossrefPubMedGoogle Scholar
  • 119 Baglioni C, Spiegelhalder K, Lombardo C et al. Neurobiological correlates of emotional processes in insomnia. J Sleep Res 2010; 19: O177
    PubMedGoogle Scholar
  • 120 Ponz A, Khatami R, Poryazova R et al. Reduced amygdala activity during aversive conditioning in human narcolepsy. Ann Neurol 2010; 67: 394-398
    PubMedGoogle Scholar
  • 121 Maquet P, Laureys S, Peigneux P. Experience-dependent changes in cerebral activation during human REM sleep. Nature Neurosci 2000; 3: 831-836
    CrossrefPubMedGoogle Scholar
  • 122 Buchsbaum M, Hazlett EA, Wu J et al. Positron emission tomography with deoxyglucose-F18 imaging of sleep. Neuropsychopharmacol 2011; 25 (5 Suppl) S50-S56
    PubMedGoogle Scholar
  • 123 Braun AR, Balkin TJ, Wesenten NJ et al. Regional cerebral blood flow throughout the sleep-wake cycle. An H2 15O PET study. Brain 1997; 120: 1173-1197
    CrossrefPubMedGoogle Scholar
  • 124 Nofzinger EA. Neuroimaging and sleep medicine. Sleep Med Rev 2005; 9: 157-172
    CrossrefPubMedGoogle Scholar
  • 125 Philips ML, Drevets WC, Rauch SL et al. Neurobiology of emotion perception I: The neural basis of normal emotion perception. Biol Psychiatry 2003; 54: 504-514
    CrossrefPubMedGoogle Scholar
  • 126 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
    CrossrefPubMedGoogle Scholar
  • 127 Benca RM, Obermeyer WH, Thistedt RA et al. Sleep and psychiatric disorders. A meta-analysis. Arch Gen Psychiatry 1992; 49: 651-668
    PubMedGoogle Scholar
  • 128 Harvey AG, Murray G, Chandler RA et al. Sleep disturbance as trans-diagnostic: Consideration of neurobiological mechanisms. Clin Psychol Rev 2011; 31: 225-235
    CrossrefPubMedGoogle Scholar
  • 129 Wulff K, Gatti S, Wettstein JG et al. Sleep and circadian rhythm disruption in psychiatric and neurodegenerative disease. Nat Rev Neurosci 2010; 11: 1-11
    PubMedGoogle Scholar
  • 130 Spoormaker VI, Montgomery P. Disturbed sleep in post-traumatic stress disorder: secondary symptom or core feature?. Sleep Med Rev 2008; 12: 169-184
    CrossrefPubMedGoogle Scholar
  • 131 Germain A, Buysse DJ, Nofzinger E. Sleep-specific mechanisms underlying posttraumatic stress disorder: integrative review and neurobiological hypothesis. Sleep Med Rev 2008; 12: 185-195
    CrossrefPubMedGoogle Scholar
  • 132 Perlis ML, Kehr EL, Smith MT et al. Temporal and stagewise distribution of high frequency EEG activity in patients with primary and secondary insomnia and in good sleeper controls. J Sleep Res 2001; 10: 93-104
    CrossrefPubMedGoogle Scholar