Skip to main content
×
Home

Subanesthetic dose of ketamine decreases prefrontal theta cordance in healthy volunteers: implications for antidepressant effect

  • J. Horacek (a1) (a2) (a3), M. Brunovsky (a1) (a2), T. Novak (a2), B. Tislerova (a3), T. Palenicek (a2) (a3), V. Bubenikova-Valesova (a1) (a2), F. Spaniel (a1) (a3), J. Koprivova (a2) (a3), P. Mohr (a1), M. Balikova (a4) and C. Hoschl (a1) (a2) (a3)...
Abstract
Background

Theta cordance is a novel quantitative electroencephalography (QEEG) measure that correlates with cerebral perfusion. A series of clinical studies has demonstrated that the prefrontal theta cordance value decreases after 1 week of treatment in responders to antidepressants and that this effect precedes clinical improvement. Ketamine, a non-competitive antagonist of N-methyl-d-aspartate (NMDA) receptors, has a unique rapid antidepressant effect but its influence on theta cordance is unknown.

Method

In a double-blind, cross-over, placebo-controlled experiment we studied the acute effect of ketamine (0.54 mg/kg within 30 min) on theta cordance in a group of 20 healthy volunteers.

Results

Ketamine infusion induced a decrease in prefrontal theta cordance and an increase in the central region theta cordance after 10 and 30 min. The change in prefrontal theta cordance correlated with ketamine and norketamine blood levels after 10 min of ketamine infusion.

Conclusions

Our data indicate that ketamine infusion immediately induces changes similar to those that monoamineric-based antidepressants induce gradually. The reduction in theta cordance could be a marker and a predictor of the fast-acting antidepressant effect of ketamine, a hypothesis that could be tested in depressive patients treated with ketamine.

Copyright
Corresponding author
*Address for correspondence: Prof. Dr J. Horacek, Ph.D., Prague Psychiatric Centre, Ustavni 91, 181 03Prague 8, Czech Republic. (Email: horacek@pcp.lf3.cuni.cz)
References
Hide All
Asada H, Fukuda Y, Tsunoda S, Yamaguchi M, Tonoike M (1999). Frontal midline theta rhythms reflect alternative activation of prefrontal cortex and anterior cingulate cortex in humans. Neuroscience Letters 274, 2932.
Bares M, Brunovsky M, Kopecek M, Novak T, Stopkova P, Kozeny J, Sos P, Krajca V, Hoschl C (2008). Early reduction in prefrontal theta QEEG cordance value predicts response to venlafaxine treatment in patients with resistant depressive disorder. European Psychiatry 23, 350355.
Bares M, Brunovsky M, Kopecek M, Stopkova P, Novak T, Kozeny J, Hoschl C (2007). Changes in QEEG prefrontal cordance as a predictor of response to antidepressants in patients with treatment resistant depressive disorder: a pilot study. Journal of Psychiatric Research 41, 319325.
Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH (2000). Antidepressant effects of ketamine in depressed patients. Biological Psychiatry 47, 351354.
Bubenikova-Valesova V, Horacek J, Vrajova M, Hoschl C (2008). Models of schizophrenia in humans and animals based on inhibition of NMDA receptors. Neuroscience and Biobehavioral Reviews 32, 10141023.
Cook IA, Leuchter AF, Morgan ML, Stubbeman W, Siegman B, Abrams M (2005). Changes in prefrontal activity characterize clinical response in SSRI nonresponders: a pilot study. Journal of Psychiatric Research 39, 461466.
Cook IA, Leuchter AF, Morgan M, Witte E, Stubbeman WF, Abrams M, Rosenberg S, Uijtdehaage SH (2002). Early changes in prefrontal activity characterize clinical responders to antidepressants. Neuropsychopharmacology 27, 120131.
Cook IA, Leuchter AF, Uijtdehaage SH, Osato S, Holschneider DH, Abrams M, Rosenberg-Thompson S (1998). Altered cerebral energy utilization in late life depression. Journal of Affective Disorders 49, 8999.
Cook IA, Leuchter AF, Witte E, Abrams M, Uijtdehaage SH, Stubbeman W, Rosenberg-Thompson S, Anderson-Hanley C, Dunkin JJ (1999). Neurophysiologic predictors of treatment response to fluoxetine in major depression. Psychiatry Research 85, 263273.
Deakin JF, Lees J, McKie S, Hallak JE, Williams SR, Dursun SM (2008). Glutamate and the neural basis of the subjective effects of ketamine: a pharmaco-magnetic resonance imaging study. Archives of General Psychiatry 65, 154164.
Du J, Machado-Vieira R, Maeng S, Martinowich K, Manji HK, Zarate J (2006). Enhancing AMPA to NMDA throughput as a convergent mechanism for antidepressant action. Drug Discovery Today: Therapeutic Strategies 3, 519526.
Ebert B, Mikkelsen S, Thorkildsen C, Borgbjerg FM (1997). Norketamine, the main metabolite of ketamine, is a non-competitive NMDA receptor antagonist in the rat cortex and spinal cord. European Journal of Pharmacology 333, 99–104.
Hetem LA, Danion JM, Diemunsch P, Brandt C (2000). Effect of a subanesthetic dose of ketamine on memory and conscious awareness in healthy volunteers. Psychopharmacology (Berlin) 152, 283288.
Hunter AM, Cook IA, Leuchter AF (2007). The promise of the quantitative electroencephalogram as a predictor of antidepressant treatment outcomes in major depressive disorder. Psychiatric Clinics of North America 30, 105124.
Ishii R, Shinosaki K, Ukai S, Inouye T, Ishihara T, Yoshimine T, Hirabuki N, Asada H, Kihara T, Robinson SE, Takeda M (1999). Medial prefrontal cortex generates frontal midline theta rhythm. Neuroreport 10, 675679.
Kennedy SH, Konarski JZ, Segal ZV, Lau MA, Bieling PJ, McIntyre RS, Mayberg HS (2007). Differences in brain glucose metabolism between responders to CBT and venlafaxine in a 16-week randomized controlled trial. American Journal of Psychiatry 164, 778788.
Knott V, Mahoney C, Kennedy S, Evans K (2000). Pre-treatment EEG and its relationship to depression severity and paroxetine treatment outcome. Pharmacopsychiatry 33, 201205.
Krystal JH, Sanacora G, Blumberg H, Anand A, Charney DS, Marek G, Epperson CN, Goddard A, Mason GF (2002). Glutamate and GABA systems as targets for novel antidepressant and mood-stabilizing treatments. Molecular Psychiatry 7 (Suppl. 1), S71S80.
Leuchter AF, Cook IA, DeBrota DJ, Hunter AM, Potter WZ, McGrouther CC, Morgan ML, Abrams M, Siegman B (2008) Changes in brain function during administration of venlafaxine or placebo to normal subjects. Clinical EEG and Neuroscience Journal 39, 175181.
Leuchter AF, Cook IA, Hunter A, Korb A (2009) Use of clinical neurophysiology for the selection of medication in the treatment of major depressive disorder: the state of the evidence. Clinical EEG and Neuroscience 40, 7883.
Leuchter AF, Cook IA, Lufkin RB, Dunkin J, Newton TF, Cummings JL, Mackey JK, Walter DO (1994). Cordance: a new method for assessment of cerebral perfusion and metabolism using quantitative electroencephalography. NeuroImage 1, 208219.
Leuchter AF, Cook IA, Uijtdehaage SH, Dunkin J, Lufkin RB, Anderson-Hanley C, Abrams M, Rosenberg-Thompson S, O'Hara R, Simon SL, Osato S, Babaie A (1997). Brain structure and function and the outcomes of treatment for depression. Journal of Clinical Psychiatry 58 (Suppl. 16), 2231.
Leuchter AF, Cook IA, Witte EA, Morgan M, Abrams M (2002). Changes in brain function of depressed subjects during treatment with placebo. American Journal of Psychiatry 159, 122129.
Leuchter AF, Uijtdehaage SH, Cook IA, O'Hara R, Mandelkern M (1999). Relationship between brain electrical activity and cortical perfusion in normal subjects. Psychiatry Research 90, 125140.
Maeng S, Zarate CA Jr., Du J, Schloesser RJ, McCammon J, Chen G, Manji HK (2008). Cellular mechanisms underlying the antidepressant effects of ketamine: role of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors. Biological Psychiatry 63, 349352.
Mathew SJ, Keegan K, Smith L (2005). Glutamate modulators as novel interventions for mood disorders. Revista Brasileira de Psiquiatria 27, 243248.
Mayberg HS (2003). Modulating dysfunctional limbic-cortical circuits in depression: towards development of brain-based algorithms for diagnosis and optimised treatment. British Medical Bulletin 65, 193207.
Mayberg HS, Liotti M, Brannan SK, McGinnis S, Mahurin RK, Jerabek PA, Silva JA, Tekell JL, Martin CC, Lancaster JL, Fox PT (1999). Reciprocal limbic-cortical function and negative mood: converging PET findings in depression and normal sadness. American Journal of Psychiatry 156, 675682.
Nuwer MR, Lehmann D, da Silva FL, Matsuoka S, Sutherling W, Vibert JF (1999). IFCN guidelines for topographic and frequency analysis of EEGs and EPs. The International Federation of Clinical Neurophysiology. Electroencephalography and Clinical Neurophysiology. Supplement 52, 1520.
Penders J, Verstraete A (2006). Laboratory guidelines and standards in clinical and forensic toxicology. Accreditation and quality assurance. Accreditation and Quality Assurance 11, 284290.
Pizzagalli D, Pascual-Marqui RD, Nitschke JB, Oakes TR, Larson CL, Abercrombie HC, Schaefer SM, Koger JV, Benca RM, Davidson RJ (2001). Anterior cingulate activity as a predictor of degree of treatment response in major depression: evidence from brain electrical tomography analysis. American Journal of Psychiatry 158, 405415.
Rowland LM, Bustillo JR, Mullins PG, Jung RE, Lenroot R, Landgraf E, Barrow R, Yeo R, Lauriello J, Brooks WM (2005). Effects of ketamine on anterior cingulate glutamate metabolism in healthy humans: a 4-T proton MRS study. American Journal of Psychiatry 162, 394396.
Salvadore G, Cornwell BR, Colon-Rosario V, Coppola R, Grillon C, Zarate CA Jr., Manji HK (2009). Increased anterior cingulate cortical activity in response to fearful faces: a neurophysiological biomarker that predicts rapid antidepressant response to ketamine. Biological Psychiatry 65, 289295.
Szabo ST, Hado-Vieira R, Yuan P, Wang Y, Wei Y, Falke C, Cirelli C, Tononi G, Manji HK, Du J (2009). Glutamate receptors as targets of protein kinase C in the pathophysiology and treatment of animal models of mania. Neuropharmacology 56, 4755.
Tishler LC, Gordon LB (1999). Ethical parameters of challenge studies inducing psychosis with ketamine. Ethics and Behavior 9, 211217.
Tsujimoto T, Shimazu H, Isomura Y (2006). Direct recording of theta oscillations in primate prefrontal and anterior cingulate cortices. Journal of Neurophysiology 95, 29873000.
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. Archives of General Psychiatry 63, 856864.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Psychological Medicine
  • ISSN: 0033-2917
  • EISSN: 1469-8978
  • URL: /core/journals/psychological-medicine
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords:

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 8
Total number of PDF views: 56 *
Loading metrics...

Abstract views

Total abstract views: 306 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 24th November 2017. This data will be updated every 24 hours.