Skip to main content
SpringerLink
Log in

Ketamine-Induced Glutamatergic Mechanisms of Sleep and Wakefulness: Insights for Developing Novel Treatments for Disturbed Sleep and Mood

  • Chapter
  • First Online:
Sleep-Wake Neurobiology and Pharmacology

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 253))

Abstract

Ketamine, a drug with rapid antidepressant effects and well-described effects on slow wave sleep (SWS), is a useful intervention for investigating sleep–wake mechanisms involved in novel therapeutics. The drug rapidly (within minutes to hours) reduces depressive symptoms in individuals with major depressive disorder (MDD) or bipolar disorder (BD), including those with treatment-resistant depression. Ketamine treatment elevates extracellular glutamate in the prefrontal cortex. Glutamate, in turn, plays a critical role as a proximal element in a ketamine-initiated molecular cascade that increases synaptic strength and plasticity, which ultimately results in rapidly improved mood. In MDD, rapid antidepressant response to ketamine is related to decreased waking as well as increased total sleep, SWS, slow wave activity (SWA), and rapid eye movement (REM) sleep. Ketamine also increases brain-derived neurotrophic factor (BDNF) levels. In individuals with MDD, clinical response to ketamine is predicted by low baseline delta sleep ratio, a measure of deficient early night production of SWS. Notably, there are important differences between MDD and BD that may be related to the effects of diagnosis or of mood stabilizers. Consistent with its effects on clock-associated molecules, ketamine alters the timing and amplitude of circadian activity patterns in rapid responders versus non-responders with MDD, suggesting that it affects mood-dependent central neural circuits. Molecular interactions between sleep homeostasis and clock genes may mediate the rapid and durable elements of clinical response to ketamine and its active metabolite.

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

Access this chapter

Log in via an institution

Institutional subscriptions

References

  • Aeschbach D, Cutler AJ, Ronda JM (2008) A role for non-rapid-eye-movement sleep homeostasis in perceptual learning. J Neurosci 28(11):2766–2772

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Agargun MY, Cartwright R (2003) REM sleep, dream variables and suicidality in depressed patients. Psychiatry Res 119(1–2):33–39

    Article  PubMed  Google Scholar 

  • Antonijevic IA (2006) Depressive disorders – is it time to endorse different pathophysiologies? Psychoneuroendocrinology 31:1–15

    Article  PubMed  Google Scholar 

  • Archer SN, Laing EE, Moller-Levet CS, van der Veen DR, Bucca G, Lazar AS, Santhi N, Slak A, Kabiljo R, von Schantz M, Smith CP, Dijk DJ (2014) Mistimed sleep disrupts circadian regulation of the human transcriptome. Proc Natl Acad Sci U S A 111(6):E682–E691

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bachmann V, Klein C, Bodenmann S, Schafer N, Berger W, Brugger P, Landolt HP (2012) The BDNF Val66Met polymorphism modulates sleep intensity: EEG frequency- and state-specificity. Sleep 35(3):335–344

    PubMed  PubMed Central  Google Scholar 

  • Bagley J, Moghaddam B (1997) Temporal dynamics of glutamate efflux in the prefrontal cortex and in the hippocampus following repeated stress: effects of pretreatment with saline or diazepam. Neuroscience 77(1):65–73

    Article  CAS  PubMed  Google Scholar 

  • Ballard ED, Ionescu DF, Vande Voort JL, Niciu MJ, Richards EM, Luckenbaugh DA, Brutsche NE, Ameli R, Furey ML, Zarate CA Jr (2014) Improvement in suicidal ideation after ketamine infusion: relationship to reductions in depression and anxiety. J Psychiatr Res 58:161–166

    Article  PubMed  Google Scholar 

  • Ballard ED, Lally N, Nugent AC, Furey ML, Luckenbaugh DA, Zarate CA Jr (2015) Neural correlates of suicidal ideation and its reduction in depression. Int J Neuropsychopharmacol 18(1)

    Article  CAS  Google Scholar 

  • Ballard ED, Vande Voort JL, Bernert RA, Luckenbaugh DA, Richards EM, Niciu MJ, Furey ML, Duncan WC, Zarate CA Jr (2016) Nocturnal wakefulness is associated with next-day suicidal ideation in major depressive disorder and bipolar disorder. J Clin Psychiatry 77(7):825–831

    Article  PubMed  PubMed Central  Google Scholar 

  • Barbini B, Benedetti F, Colombo C, Dotoli D, Bernasconi A, Cigala-Fulgosi M, Florita M, Smeraldi E (2005) Dark therapy for mania: a pilot study. Bipolar Disord 7(1):98–101

    Article  PubMed  Google Scholar 

  • Beck J, Hemmeter U, Brand S, Muheim F, Hatzinger M, Holsboer-Trachsler E (2010) Modafinil reduces microsleep during partial sleep deprivation in depressed patients. J Psychiatr Res 44(13):853–864

    Article  CAS  PubMed  Google Scholar 

  • Bellet MM, Vawter MP, Bunney BG, Bunney WE, Sassone-Corsi P (2011) Ketamine influences CLOCK:BMAL1 function leading to altered circadian gene expression. PLoS One 6(8):e23982

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Benca RM, Obermeyer WH, Thisted RA, Gillin JC (1992) Sleep and psychiatric-disorders – a metaanalysis. Arch Gen Psychiatry 49(8):651–668

    Article  CAS  PubMed  Google Scholar 

  • Benedetti F, Colombo C (2011) Sleep deprivation in mood disorders. Neuropsychobiology 64(3):141–151

    Article  PubMed  Google Scholar 

  • Benedetti F, Colombo C, Barbini B, Campori E, Smeraldi E (1999) Ongoing lithium treatment prevents relapse after total sleep deprivation. J Clin Psychopharmacol 19(3):240–245

    Article  CAS  PubMed  Google Scholar 

  • Benedetti F, Barbini B, Campori E, Fulgosi MC, Pontiggia A, Colombo C (2001) Sleep phase advance and lithium to sustain the antidepressant effect of total sleep deprivation in bipolar depression: new findings supporting the internal coincidence model? J Psychiatr Res 35(6):323–329

    Article  CAS  PubMed  Google Scholar 

  • Benedetti F, Barbini B, Colombo C, Smeraldi E (2007a) Chronotherapeutics in a psychiatric ward. Sleep Med Rev 11(6):509–522

    Article  PubMed  Google Scholar 

  • Benedetti F, Dallaspezia S, Fulgosi MC, Barbini B, Colombo C, Smeraldi E (2007b) Phase advance is an actimetric correlate of antidepressant response to sleep deprivation and light therapy in bipolar depression. Chronobiol Int 24(5):921–937

    Article  CAS  PubMed  Google Scholar 

  • Benedetti F, Calabrese G, Bernasconi A, Cadioli M, Colombo C, Dallaspezia S, Falini A, Radaelli D, Scotti G, Smeraldi E (2009) Spectroscopic correlates of antidepressant response to sleep deprivation and light therapy: a 3.0 Tesla study of bipolar depression. Psychiatry Res 173(3):238–242

    Article  CAS  PubMed  Google Scholar 

  • Benedetti F, Dallaspezia S, Lorenzi C, Pirovano A, Radaelli D, Locatelli C, Poletti S, Colombo C, Smeraldi E (2012) Gene-gene interaction of glycogen synthase kinase 3-beta and serotonin transporter on human antidepressant response to sleep deprivation. J Affect Disord 136(3):514–519

    Article  CAS  PubMed  Google Scholar 

  • Benedetti F, Riccaboni R, Locatelli C, Poletti S, Dallaspezia S, Colombo C (2014) Rapid treatment response of suicidal symptoms to lithium, sleep deprivation, and light therapy (chronotherapeutics) in drug-resistant bipolar depression. J Clin Psychiatry 75(2):133–140

    Article  CAS  PubMed  Google Scholar 

  • Berger M, Vollmann J, Hohagen F, Konig A, Lohner H, Voderholzer U, Riemann D (1997) Sleep deprivation combined with consecutive sleep phase advance as a fast-acting therapy in depression: an open pilot trial in medicated and unmedicated patients. Am J Psychiatry 154(6):870–872

    Article  CAS  PubMed  Google Scholar 

  • Bernert RA, Turvey CL, Conwell Y, Joiner TE Jr (2014) Association of poor subjective sleep quality with risk for death by suicide during a 10-year period: a longitudinal, population-based study of late life. JAMA Psychiat 71(10):1129–1137

    Article  Google Scholar 

  • BorbĂ©ly A (1982) Two process model of sleep regulation. Hum Neurobiol 1:195–204

    PubMed  Google Scholar 

  • BorbĂ©ly AA (1987) The S-deficiency hypothesis of depression and the two-process model of sleep regulation. Pharmacopsychiatry 20(1):23–29

    Article  PubMed  Google Scholar 

  • BorbĂ©ly AA, Wirz-Justice A (1982) Sleep, sleep deprivation and depression. A hypothesis derived from a model of sleep regulation. Hum Neurobiol 1(3):205–210

    PubMed  Google Scholar 

  • Breitstein J, Penix B, Roth BJ, Baxter T, Mysliwiec V (2014) Intensive sleep deprivation and cognitive behavioral therapy for pharmacotherapy refractory insomnia in a hospitalized patient. J Clin Sleep Med 10(6):689–690

    Article  PubMed  PubMed Central  Google Scholar 

  • Bunney BG, Bunney WE (2012) Rapid-acting antidepressant strategies: mechanisms of action. Int J Neuropsychopharmacol 15(5):695–713

    Article  CAS  PubMed  Google Scholar 

  • Bunney BG, Bunney WE (2013) Mechanisms of rapid antidepressant effects of sleep deprivation therapy: clock genes and circadian rhythms. Biol Psychiatry 73(12):1164–1171

    Article  CAS  PubMed  Google Scholar 

  • Campbell IG, Feinberg I (1996) NREM delta stimulation following MK-801 is a response of sleep systems. J Neurophysiol 76(6):3714–3720

    Article  CAS  PubMed  Google Scholar 

  • Chen ZY, Patel PD, Sant G, Meng CX, Teng KK, Hempstead BL, Lee FS (2004) Variant brain-derived neurotrophic factor (BDNF) (Met66) alters the intracellular trafficking and activity-dependent secretion of wild-type BDNF in neurosecretory cells and cortical neurons. J Neurosci 24(18):4401–4411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Clow A, Law R, Evans P, Vallence AM, Hodyl NA, Goldsworthy MR, Rothwell JR, Ridding MC (2014) Day differences in the cortisol awakening response predict day differences in synaptic plasticity in the brain. Stress 17(3):219–223

    Article  PubMed  Google Scholar 

  • Cohen DA, Freitas C, Tormos JM, Oberman L, Eldaief M, Pascual-Leone A (2010) Enhancing plasticity through repeated rTMS sessions: the benefits of a night of sleep. Clin Neurophysiol 121(12):2159–2164

    Article  PubMed  PubMed Central  Google Scholar 

  • Cohrs S, Tergau F, Riech S, Kastner S, Paulus W, Ziemann U, Ruther E, Hajak G (1998) High-frequency repetitive transcranial magnetic stimulation delays rapid eye movement sleep. Neuroreport 9(15):3439–3443

    Article  CAS  PubMed  Google Scholar 

  • Cornwell BR, Salvadore G, Furey M, Marquardt CA, Brutsche NE, Grillon C, Zarate CA Jr (2012) Synaptic potentiation is critical for rapid antidepressant response to ketamine in treatment-resistant major depression. Biol Psychiatry 72(7):555–561

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cuesta M, Clesse D, Pevet P, Challet E (2009) New light on the serotonergic paradox in the rat circadian system. J Neurochem 110(1):231–243

    Article  CAS  PubMed  Google Scholar 

  • Dallaspezia S, Benedetti F (2011) Chronobiological therapy for mood disorders. Expert Rev Neurother 11(7):961–970

    Article  PubMed  Google Scholar 

  • Diazgranados N, Ibrahim L, Brutsche NE, Newberg A, Kronstein P, Khalife S, Kammerer WA, Quezado Z, Luckenbaugh DA, Salvadore G, Machado-Vieira R, Manji HK, Zarate CA Jr (2010a) A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment-resistant bipolar depression. Arch Gen Psychiatry 67(8):793–802

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • DiazGranados N, Ibrahim LA, Brutsche NE, Ameli R, Henter ID, Luckenbaugh DA, Machado-Vieira R, Zarate CA Jr (2010b) Rapid resolution of suicidal ideation after a single infusion of an N-methyl-D-aspartate antagonist in patients with treatment-resistant major depressive disorder. J Clin Psychiatry 71(12):1605–1611

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dijk D-J, Czeisler CA (1995) Contribution of the circadian pacemaker and the sleep homeostat to sleep propensity, sleep structure, electroencephalographic slow waves, and sleep spindle activity in humans. J Neurosci 15:3526–3538

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Duman RS, Aghajanian GK (2012) Synaptic dysfunction in depression: potential therapeutic targets. Science 338(6103):68–72

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Duncan WC (2009) Non-pharmacological treatments and chronobiological aspects of bipolar disorder: implications for novel therapeutics. In: Zarate C, Manji H (ed) Bipolar depression: molecular neurobiology, clinical diagnosis and pharmacology. Birkhauser, Switzerland, pp 95–116

    Chapter  Google Scholar 

  • Duncan WC Jr, Zarate CA Jr (2013) Ketamine, sleep, and depression: current status and new questions. Curr Psychiatry Rep 15(9):394

    Article  PubMed  Google Scholar 

  • Duncan WC Jr, Pettigrew KD, Gillin JC (1979) REM architecture changes in bipolar and unipolar depression. Am J Psychiatry 136(11):1424–1427

    Article  PubMed  Google Scholar 

  • Duncan WC Jr, Selter J, Brutsche N, Sarasso S, Zarate CA Jr (2013a) Baseline delta sleep ratio predicts acute ketamine mood response in major depressive disorder. J Affect Disord 145(1):115–119

    Article  CAS  PubMed  Google Scholar 

  • Duncan WC, Sarasso S, Ferrarelli F, Selter J, Riedner BA, Hejazi NS, Yuan P, Brutsche N, Manji HK, Tononi G, Zarate CA (2013b) Concomitant BDNF and sleep slow wave changes indicate ketamine-induced plasticity in major depressive disorder. Int J Neuropsychopharmacol 16(2):301–311

    Article  CAS  PubMed  Google Scholar 

  • Egan MF, Kojima M, Callicott JH, Goldberg TE, Kolachana BS, Bertolino A, Zaitsev E, Gold B, Goldman D, Dean M, Lu B, Weinberger DR (2003) The BDNF val66met polymorphism affects activity-dependent secretion of BDNF and human memory and hippocampal function. Cell 112(2):257–269

    Article  CAS  PubMed  Google Scholar 

  • Eichhammer P, Kharraz A, Wiegand R, Langguth B, Frick U, Aigner JM, Hajak G (2002) Sleep deprivation in depression stabilizing antidepressant effects by repetitive transcranial magnetic stimulation. Life Sci 70(15):1741–1749

    Article  CAS  PubMed  Google Scholar 

  • Eidelman P, Talbot LS, Gruber J, Hairston I, Harvey AG (2010) Sleep architecture as correlate and predictor of symptoms and impairment in inter-episode bipolar disorder: taking on the challenge of medication effects. J Sleep Res 19(4):516–524

    Article  PubMed  PubMed Central  Google Scholar 

  • Esser SK, Hill SL, Tononi G (2007) Sleep homeostasis and cortical synchronization: I. Modeling the effects of synaptic strength on sleep slow waves. Sleep 30(12):1617–1630

    Article  PubMed  PubMed Central  Google Scholar 

  • Even C, Thuile J, Santos J, Bourgin P (2005) Modafinil as an adjunctive treatment to sleep deprivation in depression. J Psychiatry Neurosci 30(6):432–433

    PubMed  PubMed Central  Google Scholar 

  • Faraguna U, Vyazovskiy VV, Nelson AB, Tononi G, Cirelli C (2008) A causal role for brain-derived neurotrophic factor in the homeostatic regulation of sleep. J Neurosci 28(15):4088–4095

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Feinberg I, Campbell IG (1993) Ketamine administration during waking increases delta EEG intensity in rat sleep. Neuropsychopharmacology 9:41–48

    Article  CAS  PubMed  Google Scholar 

  • Franken P (2013) A role for clock genes in sleep homeostasis. Curr Opin Neurobiol 23(5):864–872

    Article  CAS  PubMed  Google Scholar 

  • Franken P, Dijk DJ (2009) Circadian clock genes and sleep homeostasis. Eur J Neurosci 29(9):1820–1829

    Article  CAS  PubMed  Google Scholar 

  • Frey S, Birchler-Pedross A, Hofstetter M, Brunner P, Gotz T, Munch M, Blatter K, Knoblauch V, Wirz-Justice A, Cajochen C (2012) Young women with major depression live on higher homeostatic sleep pressure than healthy controls. Chronobiol Int 29:278–294

    Article  PubMed  Google Scholar 

  • Giese M, Beck J, Brand S, Muheim F, Hemmeter U, Hatzinger M, Holsboer-Trachsler E, Eckert A (2014) Fast BDNF serum level increase and diurnal BDNF oscillations are associated with therapeutic response after partial sleep deprivation. J Psychiatr Res 59:1–7

    Article  PubMed  Google Scholar 

  • Gillin JC, Duncan W, Pettigrew KD, Frankel BL, Snyder F (1979) Successful separation of depressed, normal, and insomniac subjects by EEG sleep data. Arch Gen Psychiatry 36(1):85–90

    Article  CAS  PubMed  Google Scholar 

  • Gorgulu Y, Caliyurt O (2009) Rapid antidepressant effects of sleep deprivation therapy correlates with serum BDNF changes in major depression. Brain Res Bull 80(3):158–162

    Article  CAS  PubMed  Google Scholar 

  • Gould TD, Manji HK (2002) The Wnt signaling pathway in bipolar disorder. Neuroscientist 8(5):497–511

    Article  CAS  PubMed  Google Scholar 

  • Gould TD, Manji HK (2005) Glycogen synthase kinase-3: a putative molecular target for lithium mimetic drugs. Neuropsychopharmacology 30(7):1223–1237

    Article  CAS  PubMed  Google Scholar 

  • Gunnell D, Chang SS, Tsai MK, Tsao CK, Wen CP (2013) Sleep and suicide: an analysis of a cohort of 394,000 Taiwanese adults. Soc Psychiatry Psychiatr Epidemiol 48(9):1457–1465

    Article  PubMed  Google Scholar 

  • Haile CN, Murrough JW, Iosifescu DV, Chang LC, Al Jurdi RK, Foulkes A, Iqbal S, Mahoney JJ 3rd, De La Garza R 2nd, Charney DS, Newton TF, Mathew SJ (2014) Plasma brain derived neurotrophic factor (BDNF) and response to ketamine in treatment-resistant depression. Int J Neuropsychopharmacol 17(2):331–336

    Article  CAS  PubMed  Google Scholar 

  • Hefti K, Holst SC, Sovago J, Bachmann V, Buck A, Ametamey SM, Scheidegger M, Berthold T, Gomez-Mancilla B, Seifritz E, Landolt HP (2013) Increased metabotropic glutamate receptor subtype 5 availability in human brain after one night without sleep. Biol Psychiatry 73(2):161–168

    Article  CAS  PubMed  Google Scholar 

  • Hemmeter U, Hatzinger M, Brand S, Holsboer-Trachsler E (2007) Effect of flumazenil-augmentation on microsleep and mood in depressed patients during partial sleep deprivation. J Psychiatr Res 41(10):876–884

    Article  PubMed  Google Scholar 

  • Hemmeter UM, Hemmeter-Spernal J, Krieg JC (2010) Sleep deprivation in depression. Expert Rev Neurother 10(7):1101–1115

    Article  PubMed  Google Scholar 

  • Hiltunen L, Suominen K, Lonnqvist J, Partonen T (2011) Relationship between daylength and suicide in Finland. J Circadian Rhythms 9:10

    Article  PubMed  PubMed Central  Google Scholar 

  • Homayoun H, Moghaddam B (2007) NMDA receptor hypofunction produces opposite effects on prefrontal cortex interneurons and pyramidal neurons. J Neurosci 27(43):11496–11500

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Huber R, Ghilardi MF, Massimini M, Tononi G (2004) Local sleep and learning. Nature 430(6995):78–81

    Article  CAS  PubMed  Google Scholar 

  • Huber R, Ghilardi MF, Massimini M, Ferrarelli F, Riedner BA, Peterson MJ, Tononi G (2006) Arm immobilization causes cortical plastic changes and locally decreases sleep slow wave activity. Nat Neurosci 9:1169–1176

    Article  CAS  PubMed  Google Scholar 

  • Huber R, Tononi G, Cirelli C (2007) Exploratory behavior, cortical BDNF expression, and sleep homeostasis. Sleep 30(2):129–139

    Article  PubMed  Google Scholar 

  • Huber R, Maki H, Rosanova M, Casarotto S, Canali P, Casali AG, Tononi G, Massimini M (2013) Human cortical excitability increases with time awake. Cereb Cortex 23(2):332–338

    Article  PubMed  Google Scholar 

  • Ibrahim L, Duncan WC, Luckenbaugh DA, Yuan P, Machado-Vieira R, Zarate CAJ (2011) Rapid antidepressant changes with sleep deprivation in major depressive disorder are associated with changes in vascular endothelial growth factor (VEGF): a pilot study. Brain Res Bull 86:129–133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ionescu DF, Luckenbaugh DA, Niciu MJ, Richards EM, Zarate CA Jr (2015) A single infusion of ketamine improves depression scores in patients with anxious bipolar depression. Bipolar Disord 17:438–443

    Article  CAS  PubMed  Google Scholar 

  • JC W, Kelsoe JR, Schachat C, Bunney BG, DeModena A, Golshan S, Gillin JC, Potkin SG, Bunney WE (2009) Rapid and sustained antidepressant response with sleep deprivation and chronotherapy in bipolar disorder. Biol Psychiatry 66(3):298–301

    Article  CAS  Google Scholar 

  • Kasper S, Hamon M (2009) Beyond the monoaminergic hypothesis: agomelatine, a new antidepressant with an innovative mechanism of action. World J Biol Psychiatry 10(2):117–126

    Article  PubMed  Google Scholar 

  • Kasper S, Hajak G, Wulff K, Hoogendijk WJ, Montejo AL, Smeraldi E, Rybakowski JK, Quera-Salva MA, Wirz-Justice AM, Picarel-Blanchot F, Bayle FJ (2010) Efficacy of the novel antidepressant agomelatine on the circadian rest-activity cycle and depressive and anxiety symptoms in patients with major depressive disorder: a randomized, double-blind comparison with sertraline. J Clin Psychiatry 71(2):109–120

    Article  CAS  PubMed  Google Scholar 

  • Kreuzer PM, Langguth B, Schecklmann M, Eichhammer P, Hajak G, Landgrebe M (2012) Can repetitive transcranial magnetic stimulation prolong the antidepressant effects of sleep deprivation? Brain Stimul 5(2):141–147

    Article  PubMed  Google Scholar 

  • Kuhn M, Wolf E, Maier JG, Mainberger F, Feige B, Schmid H, Burklin J, Maywald S, Mall V, Jung NH, Reis J, Spiegelhalder K, Kloppel S, Sterr A, Eckert A, Riemann D, Normann C, Nissen C (2016) Sleep recalibrates homeostatic and associative synaptic plasticity in the human cortex. Nat Commun 7:12455

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kupfer DJ, Ehlers CL (1989) Two roads to rapid eye movement latency. Arch Gen Psychiatry 46(10):945–948

    Article  CAS  PubMed  Google Scholar 

  • Kupfer DJ, Ulrich RF, Coble PA, Jarrett DB, Grochocinski VJ, Doman J, Matthews G, BorbĂ©ly AA (1985) Electroencephalographic sleep of younger depressives. Comparison with normals. Arch Gen Psychiatry 42(8):806–810

    Article  CAS  PubMed  Google Scholar 

  • Laje G, Lally N, Mathews D, Brutsche N, Chemerinski A, Akula N, Kelmendi B, Simen A, McMahon FJ, Sanacora G, Zarate C Jr (2012) Brain-derived neurotrophic factor Val66Met polymorphism and antidepressant efficacy of ketamine in depressed patients. Biol Psychiatry 72(11):e27–e28

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lam RW, Kennedy SH (2015) STAR*D and measurement-based care for depression: don’t toss out the baby. Can J Psychiatry 60(1):6–8

    Article  PubMed  PubMed Central  Google Scholar 

  • Lenox RH, Gould TD, Manji HK (2002) Endophenotypes in bipolar disorder. Am J Med Genet 114(4):391–406

    Article  PubMed  Google Scholar 

  • Lewy AJ, Emens JS, Sack RL, Hasler BP, Bernert RA (2002) Low, but not high, doses of melatonin entrained a free-running blind person with a long circadian period. Chronobiol Int 19(3):649–658

    Article  CAS  PubMed  Google Scholar 

  • Li N, Lee B, Liu RJ, Banasr M, Dwyer JM, Iwata M, Li XY, Aghajanian G, Duman RS (2010) mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science 329(5994):959–964

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li SX, Liu LJ, LZ X, Gao L, Wang XF, Zhang JT, Lu L (2013) Diurnal alterations in circadian genes and peptides in major depressive disorder before and after escitalopram treatment. Psychoneuroendocrinology 38(11):2789–2799

    Article  CAS  PubMed  Google Scholar 

  • Linkowski P, Kerkhofs M, Rielaert C, Mendlewicz J (1986) Sleep during mania in manic-depressive males. Eur Arch Psychiatry Neurol Sci 235(6):339–341

    Article  CAS  PubMed  Google Scholar 

  • Machado-Vieira R, Baumann J, Wheeler-Castillo C, Latov D, Henter ID, Salvadore G, Zarate CA (2010) The timing of antidepressant effects: a comparison of diverse pharmacological and somatic treatments. Pharmaceuticals (Basel) 3:19–41

    Article  CAS  Google Scholar 

  • Maeng S, Zarate CA Jr (2007) The role of glutamate in mood disorders: results from the ketamine in major depression study and the presumed cellular mechanism underlying its antidepressant effects. Curr Psychiatry Rep 9(6):467–474

    Article  PubMed  Google Scholar 

  • McCarthy MJ, Nievergelt CM, Kelsoe JR, Welsh DK (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  CAS  PubMed  PubMed Central  Google Scholar 

  • Murck H, Schubert MI, Schmid D, Schussler P, Steiger A, Auer DP (2009) The glutamatergic system and its relation to the clinical effect of therapeutic-sleep deprivation in depression – an MR spectroscopy study. J Psychiatr Res 43(3):175–180

    Article  PubMed  Google Scholar 

  • Murrough JW, Perez AM, Pillemer S, Stern J, Parides MK, Aan Het Rot M, Collins KA, Mathew SJ, Charney DS, Iosifescu DV (2013) Rapid and longer-term antidepressant effects of repeated ketamine infusions in treatment-resistant major depression. Biol Psychiatry 74:250–256

    Article  CAS  PubMed  Google Scholar 

  • Murrough JW, Soleimani L, DeWilde KE, Collins KA, Lapidus KA, Iacoviello BM, Lener M, Kautz M, Kim J, Stern JB, Price RB, Perez AM, Brallier JW, Rodriguez GJ, Goodman WK, Iosifescu DV, Charney DS (2015) Ketamine for rapid reduction of suicidal ideation: a randomized controlled trial. Psychol Med 45(16):3571–3580

    Article  CAS  PubMed  Google Scholar 

  • Perlis ML, Grandner MA, Brown GK, Basner M, Chakravorty S, Morales KH, Gehrman PR, Chaudhary NS, Thase ME, Dinges DF (2016) Nocturnal wakefulness as a previously unrecognized risk factor for suicide. J Clin Psychiatry 77(6):726–733

    Article  Google Scholar 

  • Peyron C, Tighe DK, van den Pol AN, de Lecea L, Heller HC, Sutcliffe JG, Kilduff TS (1998) Neurons containing hypocretin (orexin) project to multiple neuronal systems. J Neurosci 18(23):9996–10015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Pigeon WR, Pinquart M, Conner K (2012) Meta-analysis of sleep disturbance and suicidal thoughts and behaviors. J Clin Psychiatry 73(9):e1160–e1167

    Article  PubMed  Google Scholar 

  • Pillai V, Kalmbach DA, Ciesla JA (2011) A meta-analysis of electroencephalographic sleep in depression: evidence for genetic biomarkers. Biol Psychiatry 70(10):912–919

    Article  PubMed  Google Scholar 

  • Posternak MA, Zimmerman M (2005) Is there a delay in the antidepressant effect? A meta-analysis. J Clin Psychiatry 66(2):148–158

    Article  CAS  PubMed  Google Scholar 

  • Price RB, Nock MK, Charney DS, Mathew SJ (2009) Effects of intravenous ketamine on explicit and implicit measures of suicidality in treatment-resistant depression. Biol Psychiatry 66(5):522–526

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Price RB, Iosifescu DV, Murrough JW, Chang LC, Al Jurdi RK, Iqbal SZ, Soleimani L, Charney DS, Foulkes AL, Mathew SJ (2014) Effects of ketamine on explicit and implicit suicidal cognition: a randomized controlled trial in treatment-resistant depression. Depress Anxiety 31(4):335–343

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Quitkin FM, Rabkin JG, Stewart JW, McGrath PJ, Harrison W, Davies M, Goetz R, Puig-Antich J (1985) Sleep of atypical depressives. J Affect Disord 8:61–67

    Article  CAS  PubMed  Google Scholar 

  • Roecklein KA, Rohan KJ, Duncan WC, Rollag MD, Rosenthal NE, Lipsky RH, Provencio I (2009) A missense variant (P10L) of the melanopsin (OPN4) gene in seasonal affective disorder. J Affect Disord 114:279–285

    Article  CAS  PubMed  Google Scholar 

  • Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, Niederehe G, Thase ME, Lavori PW, Lebowitz BD, McGrath PJ, Rosenbaum JF, Sackeim HA, Kupfer DJ, Luther J, Fava M (2006) Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry 163(11):1905–1917

    Article  PubMed  Google Scholar 

  • Sabo E, Reynolds CF 3rd, Kupfer DJ, Berman SR (1991) Sleep, depression, and suicide. Psychiatry Res 36(3):265–277

    Article  CAS  PubMed  Google Scholar 

  • Saeki T, Nakamura M, Hirai N, Noda Y, Hayasaka S, Iwanari H, Hirayasu Y (2013) Localized potentiation of sleep slow-wave activity induced by prefrontal repetitive transcranial magnetic stimulation in patients with a major depressive episode. Brain Stimul 6(3):390–396

    Article  PubMed  Google Scholar 

  • Sahlem GL, Kalivas B, Fox JB, Lamb K, Roper A, Williams EN, Williams NR, Korte JE, Zuschlag ZD, El Sabbagh S, Guille C, Barth KS, Uhde TW, George MS, Short EB (2014) Adjunctive triple chronotherapy (combined total sleep deprivation, sleep phase advance, and bright light therapy) rapidly improves mood and suicidality in suicidal depressed inpatients: an open label pilot study. J Psychiatr Res 59:101–107

    Article  PubMed  PubMed Central  Google Scholar 

  • Sakurai T (2007) The neural circuit of orexin (hypocretin): maintaining sleep and wakefulness. Nat Rev Neurosci 8(3):171–181

    Article  CAS  PubMed  Google Scholar 

  • Tononi G, Cirelli C (2006) Sleep function and synaptic homeostasis. Sleep Med Rev 10(1):49–62

    Article  PubMed  Google Scholar 

  • Uz T (2005) Effect of fluoxetine and cocaine on the expression of clock genes in the mouse hippocampus and striatum. Neuroscience 134:1309–1316

    Article  CAS  PubMed  Google Scholar 

  • Vande Voort JL, Ballard ED, Luckenbaugh DA, Bernert RA, Richards EM, Niciu MJ, Park L, Machado-Vieira R, Duncan WC, Zarate CA (2016) Antisuicidal response following ketamine infusion is associated with decreased nighttime wakefulness in major depressive disorder and bipolar disorder. J Clin Psychiatry. Doi: 10.4088/JCP.15m10440. [Epub ahead of print]

    Article  PubMed  PubMed Central  Google Scholar 

  • Verkes RJ, Kerkhof GA, Beld E, Hengeveld MW, van Kempen GM (1996) Suicidality, circadian activity rhythms and platelet serotonergic measures in patients with recurrent suicidal behaviour. Acta Psychiatr Scand 93(1):27–34

    Article  CAS  PubMed  Google Scholar 

  • Vyazovskiy VV, Riedner BA, Cirelli C, Tononi G (2007) Sleep homeostasis and cortical synchronization: II. A local field potential study of sleep slow waves in the rat. Sleep 30(12):1631–1642

    Article  PubMed  PubMed Central  Google Scholar 

  • Wehr TA, Goodwin FK (eds) (1983) Circadian rhythms in psychiatry. Psychobiology and psychopathology, vol 2. Boxwood Press, New York, NY

    Google Scholar 

  • Wehr TA, Turner EH, Shimada JM, Lowe CH, Barker C, Leibenluft E (1998) Treatment of a rapidly cycling bipolar patient by using extended bed rest and darkness to stabilize the timing and duration of sleeo. Biol Psychiatry 43:822–828

    Article  CAS  PubMed  Google Scholar 

  • Wiegand M, Berger M, Zulley J, von Zerssen D (1986) The effect of trimipramine on sleep in patients with major depressive disorder. Pharmacopsychiatry 19:198–199

    Article  CAS  Google Scholar 

  • Wiegand M, Berger M, Zulley J, Lauer C, von Zerssen D (1987) The influence of daytime naps on the therapeutic effect of sleep deprivation. Biol Psychiatry 22(3):389–392

    Article  CAS  PubMed  Google Scholar 

  • Wiegand M, Riemann D, Schreiber W, Lauer CJ, Berger M (1993) Effect of morning and afternoon naps on mood after total sleep deprivation in patients with major depression. Biol Psychiatry 33:467–476

    Article  CAS  PubMed  Google Scholar 

  • Willie JT, Chemelli RM, Sinton CM, Yanagisawa M (2001) To eat or to sleep? Orexin in the regulation of feeding and wakefulness. Annu Rev Neurosci 24:429–458

    Article  CAS  PubMed  Google Scholar 

  • Wirz-Justice A, Terman M (2012) Chronotherapeutics (light and wake therapy) as a class of interventions for affective disorders. Handb Clin Neurol 106:697–713

    Article  PubMed  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  CAS  PubMed  Google Scholar 

  • Wirz-Justice A, Quinto C, Cajochen C, Werth E, Hock C (1999) A rapid-cycling bipolar patient treated with long nights, bedrest and light. Biol Psychiatry 45:1075–1077

    Article  CAS  PubMed  Google Scholar 

  • Wright RA, Johnson BG, Zhang C, Salhoff C, Kingston AE, Calligaro DO, Monn JA, Schoepp DD, Marek GJ (2013) CNS distribution of metabotropic glutamate 2 and 3 receptors: transgenic mice and [(3)H]LY459477 autoradiography. Neuropharmacology 66:89–98

    Article  CAS  PubMed  Google Scholar 

  • Wu JC, Kelsoe JR, Schachat C, Bunney BG, DeModena A, Golshan S, Gillin JC, Potkin SG, Bunney WE (2009) Rapid and sustained antidepressant response with sleep deprivation and chronotherapy in bipolar disorder. Biol Psychiatry 66 (3):298–301

    Article  CAS  PubMed  Google Scholar 

  • Zanos P, Moaddel R, Morris PJ, Georgiou P, Fischell J, Elmer GI, Alkondon M, Yuan P, Pribut HJ, Singh NS, Dossou KS, Fang Y, Huang XP, Mayo CL, Wainer IW, Albuquerque EX, Thompson SM, Thomas CJ, Zarate CA Jr, Gould TD (2016) NMDAR inhibition-independent antidepressant actions of ketamine metabolites. Nature 533(7604):481–486

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zarate CA Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, Charney DS, Manji HK (2006) A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry 63(8):856–864

    Article  CAS  PubMed  Google Scholar 

  • Zarate CA Jr, Brutsche NE, Ibrahim L, Franco-Chaves J, Diazgranados N, Cravchik A, Selter J, Marquardt CA, Liberty V, Luckenbaugh DA (2012) Replication of ketamine's antidepressant efficacy in bipolar depression: a randomized controlled add-on trial. Biol Psychiatry 71(11):939–946

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao C, Eisinger BE, Driessen TM, Gammie SC (2014) Addiction and reward-related genes show altered expression in the postpartum nucleus accumbens. Front Behav Neurosci 8:388

    PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The authors thank the 7SE research unit and staff for their support. Ioline Henter (NIMH) provided invaluable editorial assistance.

Author information

Authors and Affiliations

  1. Experimental Therapeutics and Pathophysiology Branch, National Institute of Mental Health, National Institute of Health, Bethesda, MD, 20892, USA

    Wallace C. Duncan Jr., Elizabeth D. Ballard & Carlos A. Zarate

Authors
  1. Wallace C. Duncan Jr.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elizabeth D. Ballard
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Carlos A. Zarate
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wallace C. Duncan Jr. .

Editor information

Editors and Affiliations

  1. Human Sleep Psychopharmacology Laboratory, Institute of Pharmacology and Toxicology, University of ZĂĽrich, ZĂĽrich, Switzerland

    Hans-Peter Landolt

  2. Surrey Sleep Research Centre, Faculty of Health and Medical Sciences, University of Surrey, Guildford, UK

    Derk-Jan Dijk

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this chapter

Cite this chapter

Duncan, W.C., Ballard, E.D., Zarate, C.A. (2017). Ketamine-Induced Glutamatergic Mechanisms of Sleep and Wakefulness: Insights for Developing Novel Treatments for Disturbed Sleep and Mood. In: Landolt, HP., Dijk, DJ. (eds) Sleep-Wake Neurobiology and Pharmacology . Handbook of Experimental Pharmacology, vol 253. Springer, Cham. https://doi.org/10.1007/164_2017_51

Download citation

Publish with us

Policies and ethics

Search

Navigation