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Chapter 2 - Mechanism of Action of ECT

Published online by Cambridge University Press:  27 June 2019

By
Philip J Cowen
Edited by
I. Nicol Ferrier  and
Jonathan Waite
I. Nicol Ferrier
Affiliation:
University of Newcastle upon Tyne
Jonathan Waite
Affiliation:
University of Nottingham
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Summary

Electroconvulsive therapy (ECT) possesses several key therapeutic actions, having antidepressant, anti-manic and antipsychotic effects. The adverse effects of ECT, particularly loss of autobiographical memories, are also of great clinical importance. Whether the same ‘mechanism’ underpins all these properties is unknown. Most information about the mechanistic effects of ECT has been obtained in relation to the treatment of depression and the current review will focus on this area.

Type
Chapter
Information
The ECT Handbook , pp. 13 - 23
Publisher: Cambridge University Press
Print publication year: 2019

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References

Abbott, C C, Jones, T, Lemke, N T, et al. (2014) Hippocampal structural and functional changes associated with electroconvulsive therapy response. Translational Psychiatry, 4, e483.Google Scholar
Ainsworth, K, Smith, S E, Zetterström, T S, et al. (1998) Effect of antidepressant drugs on dopamine D1 and D2 receptor expression and dopamine release in the nucleus accumbens of the rat. Psychopharmacology 140, 470–7.Google Scholar
Anderson, I M, Fergusson, G M (2013) Mechanism of action of ECT. In The ECT Handbook (eds Waite, J and Easton, A), pp. 1–7. Royal College of Psychiatrists.Google Scholar
Anderson, I M, Blamire, A, Branton, T, et al. (2017) Ketamine augmentation of electroconvulsive therapy to improve neuropsychological and clinical outcomes in depression (Ketamine-ECT): a multicentre, double-blind, randomised, parallel group, superiority trial. Lancet Psychiatry, 4, 365–77.CrossRefGoogle ScholarPubMed
Arnone, D, McIntosh, A M, Ebmeier, K P, et al. (2012) Magnetic resonance imaging studies in unipolar depression: systematic review and meta-regression analyses. European Neuropsychopharmacology, 22, 1–6.Google Scholar
Arnone, D, McKie, S, Elliott, R, et al. (2013) State-dependent changes in hippocampal grey matter in depression. Molecular Psychiatry, 18, 1265–72.Google Scholar
Arnone, D, Mumuni, A N, Jauhar, S, et al. (2015) Indirect evidence of selective glial involvement in glutamate-based mechanisms of mood regulation in depression: meta-analysis of absolute prefrontal neuro-metabolic concentrations. European Neuropsychopharmacology, 25, 1109–17.Google Scholar
Bouckaert, F, Sienaert, P, Obbels, J, et al. (2014) ECT: its brain enabling effects: a review of electroconvulsive therapy–induced structural brain plasticity. Journal of ECT, 30, 143–51.Google Scholar
Carvalho, L A, Torre, J P, Papadopoulos, A S, et al. (2013) Lack of clinical therapeutic benefit of antidepressants is associated overall activation of the inflammatory system. Journal of Affective Disorders 148, 136–40.Google Scholar
Cassidy, F, Weiner, R D, Cooper, T B, et al. (2010) Combined catecholamine and indoleamine depletion following response to ECT. British Journal of Psychiatry, 196, 493–4.Google Scholar
Cowen, P J, Anderson, I M (2015). New approaches to treating resistant depression. BJPsych Advances, 21, 315–23.Google Scholar
Cowen, P J, Browning, M (2015) What has serotonin to do with depression? World Psychiatry, 14, 158–60.Google Scholar
Cowen, P, Harrison, P, Burns, T (2012) Shorter Oxford Textbook of Psychiatry. Oxford University Press, Oxford, UK.Google Scholar
Czuczwar, S J, Patsalos, P N (2001) The new generation of GABA enhancers. CNS Drugs, 15, 339–50.Google Scholar
Davachi, L (2006) Item, context and relational episodic encoding in humans. Current Opinion in Neurobiology, 16, 693–700.Google Scholar
Dichter, G S, Gibbs, D, Smoski, M J (2015) A systematic review of relations between resting-state functional-MRI and treatment response in major depressive disorder. Journal Affective Disorders, 172, 8–17.Google Scholar
Dong, C, Zhang, J C, Yao, W, et al. (2016) Effects of escitalopram, R-citalopram, and reboxetine on serum levels of tumor necrosis factor-α, interleukin-10, and depression-like behavior in mice after lipopolysaccharide administration. Pharmacology Biochemistry and Behavior, 144, 7–12.Google Scholar
Duman, R S, Voleti, B (2012) Signaling pathways underlying the pathophysiology and treatment of depression: novel mechanisms for rapid-acting agents. Trends in Neurosciences, 35, 47–56.Google Scholar
Godlewska, B R, Near, J, Cowen, P J (2015) Neurochemistry of major depression: a study using magnetic resonance spectroscopy. Psychopharmacology, 232, 501–7.Google Scholar
Goodwin, G M, Green, A R, Johnson, P (1984) 5‐HT2 receptor characteristics in frontal cortex and 5‐HT2 receptor‐mediated head‐twitch behaviour following antidepressant treatment to mice. British Journal of Pharmacology, 83, 235–42.Google Scholar
Goodwin, G M, Souza, R J, Green, A R (1987) Attenuation by electroconvulsive shock and antidepressant drugs of the 5-HT 1A receptor-mediated hypothermia and serotonin syndrome produced by 8-OH-DPAT in the rat. Psychopharmacology, 91, 500–5.Google Scholar
Hannestad, J, DellaGioia, N, Bloch, M (2011) The effect of antidepressant medication treatment on serum levels of inflammatory cytokines: a meta-analysis. Neuropsychopharmacology, 36, 2452–9.Google Scholar
Harmer, C, Duman, R S, Cowen, P (2017) How do antidepressants work? New perspectives for refining treatment approaches of the future. Lancet Psychiatry (in press).Google Scholar
Järventausta, K, Sorri, A, Kampman, O, et al.(2017) Changes in interleukin‐6 levels during electroconvulsive therapy may reflect the therapeutic response in major depression. Acta Psychiatrica Scandinavica, 135, 87–92.Google Scholar
Joshi, S H, Espinoza, R T, Pirnia, T, et al. (2016) Structural plasticity of the hippocampus and amygdala induced by electroconvulsive therapy in major depression. Biological Psychiatry, 15, 282–92.Google Scholar
Kaiser, R H, Whitfield-Gabrieli, S, Dillon, D G, et al. (2015) Dynamic resting-state functional connectivity in major depression. Neuropsychopharmacology, 41, 1822–30.Google Scholar
Kolshus, E, Jelovac, A, McLoughlin, D M (2017) Bitemporal v. high-dose right unilateral electroconvulsive therapy for depression: a systematic review and meta-analysis of randomized controlled trials. Psychological Medicine, 47, 518–30.Google Scholar
Lally, J, Tully, J, Robertson, D, et al. (2016) Augmentation of clozapine with electroconvulsive therapy in treatment resistant schizophrenia: a systematic review and meta-analysis. Schizophrenia Research, 171, 215–24.Google Scholar
Landau, A M, Chakravarty, M M, Clark, C M, et al. (2011) Electroconvulsive therapy alters dopamine signaling in the striatum of non-human primates. Neuropsychopharmacology, 36, 511–18.Google Scholar
Lanzenberger, R, Baldinger, P, Hahn, A, et al. (2013) Global decrease of serotonin-1A receptor binding after electroconvulsive therapy in major depression measured by PET. Molecular Psychiatry, 18, 93–100.Google Scholar
Löscher, W (2002) Basic pharmacology of valproate. CNS Drugs, 16, 669–94.Google Scholar
McGirr, A, Berlim, M T, Bond, D J, et al. (2015) A systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials of ketamine in the rapid treatment of major depressive episodes. Psychological Medicine, 45, 693–704.Google Scholar
McGirr, A, Berlim, M T, Bond, D J, et al. (2017) Adjunctive ketamine in electroconvulsive therapy: updated systematic review and meta-analysis. British Journal of Psychiatry, 210, 403-407.Google Scholar
Martinowich, K, Manji, H, Lu, B (2007) New insights into BDNF function in depression and anxiety. Nature Neuroscience, 10, 1089–93.Google Scholar
Narang, P U, Glowacki, A, Lippmann, S T (2014) Electroconvulsive therapy intervention for Parkinson’s disease. Innovations in Clinical Neuroscience, 12, 25–8.Google Scholar
Newport, D J, Carpenter, L L, McDonald, W M, et al. (2015) Ketamine and other NMDA antagonists: early clinical trials and possible mechanisms in depression. American Journal of Psychiatry, 172, 950–66.Google Scholar
Njau, S, Joshi, S H, Espinoza, R, et al. (2017) Neurochemical correlates of rapid treatment response to electroconvulsive therapy in patients with major depression. Journal of Psychiatry & Neuroscience, 42, 6–16.Google Scholar
Oh, D H, Son, H, Hwang, S, Kim, S H (2012), Kim SH. Neuropathological abnormalities of astrocytes, GABAergic neurons, and pyramidal neurons in the dorsolateral prefrontal cortices of patients with major depressive disorder. European Neuropsychopharmacology, 22, 330–8.Google Scholar
Perrin, J S, Merz, S, Bennett, D M, et al. (2012) Electroconvulsive therapy reduces frontal cortical connectivity in severe depressive disorder. Proceedings of the National Academy of Sciences, 109, 5464–8.Google Scholar
Pfleiderer, B, Michael, N, Erfurth, A, et al. (2003) Effective electroconvulsive therapy reverses glutamate/glutamine deficit in the left anterior cingulum of unipolar depressed patients. Psychiatry Research: Neuroimaging, 122, 185–92.Google Scholar
Price, J L, Drevets, W C (2012) Neural circuits underlying the pathophysiology of mood disorders, Trends in Cognitive Sciences, 16, 61–71.Google Scholar
Raison, C L, Miller, A H (2011) Is depression an inflammatory disorder? Current Psychiatry Reports, 13, 467–75.CrossRefGoogle ScholarPubMed
Raison, C L, Rutherford, R E, Woolwine, B J, et al. (2013) A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry, 70, 31–41.Google Scholar
Rocha, R B, Dondossola, E R, Grande, A J, et al. (2016) Increased BDNF levels after electroconvulsive therapy in patients with major depressive disorder: a meta-analysis study. Journal of Psychiatric Research, 83, 47–53.Google Scholar
Ruhé, H G, Mason, N S, Schene, A H (2007) Mood is indirectly related to serotonin, norepinephrine and dopamine levels in humans: a meta-analysis of monoamine depletion studies. Molecular Psychiatry, 12, 331–59.Google Scholar
Rush, G, O’Donovan, A, Nagle, L, et al. (2016) Alteration of immune markers in a group of melancholic depressed patients and their response to electroconvulsive therapy. Journal of Affective Disorders, 205, 60–8.Google Scholar
Sackeim, H A, Prudic, J, Devanand, D P, et al. (2000) A prospective, randomized, double-blind comparison of bilateral and right unilateral electroconvulsive therapy at different stimulus intensities. Archives of General Psychiatry, 57, 425–34.Google Scholar
Saijo, T, Takano, A, Suhara, T, et al. (2010a) Effect of electroconvulsive therapy on 5-HT1A receptor binding in patients with depression: a PET study with [11C] WAY 100635. International Journal of Neuropsychopharmacology, 13, 785–91.Google Scholar
Saijo, T, Takano, A, Suhara, T, et al. (2010b) Electroconvulsive therapy decreases dopamine D2 receptor binding in the anterior cingulate in patients with depression: a controlled study using positron emission tomography with radioligand [11 C] FLB 457. Journal of Clinical Psychiatry, 71, 793–9.Google Scholar
Sanacora, G, Fenton, L R, Fasula, M K, et al. (2006) Cortical γ-aminobutyric acid concentrations in depressed patients receiving cognitive behavioral therapy. Biological Psychiatry, 59, 284–6.CrossRefGoogle ScholarPubMed
Sanacora, G, Mason, G F, Rothman, D L, et al. (2002) Increased occipital cortex GABA concentrations in depressed patients after therapy with selective serotonin reuptake inhibitors. American Journal of Psychiatry, 159, 663–5.Google Scholar
Sanacora, G, Mason, G F, Rothman, D L, et al. (2003) Increased cortical GABA concentrations in depressed patients receiving ECT. American Journal of Psychiatry, 160, 577–9.Google Scholar
Sanchez Gonzalez, R, Alcoverro, O, Pagerols, J, et al. (2009) Electrophysiological mechanisms of action of electroconvulsive therapy. Actas Españolas de Psiquiatría, 37, 343–51.Google Scholar
Schür, R R, Draisma, L W, Wijnen, J P, et al. (2016) Brain GABA levels across psychiatric disorders: A systematic literature review and meta‐analysis of 1H‐MRS studies. Human Brain Mapping, 37, 3337–52.Google Scholar
Schwieler, L, Samuelsson, M, Frye, M A et al. (2016) Electroconvulsive therapy suppresses the neurotoxic branch of the kynurenine pathway in treatment resistant depressed patients. Journal of Inflammation, 13, 51.Google Scholar
Setiawan, E, Wilson, A A, Mizrahi, R, et al. (2015) Role of translocator protein density, a marker of neuroinflammation, in the brain during major depressive episodes. JAMA Psychiatry 72, 268–75.Google Scholar
Sheline, Y I, Barch, D M, Price, J L, et al. (2009) The default mode network and self-referential processes in depression. Proceedings of the National Academy of Sciences, 106, 942–7.Google Scholar
Sheline, Y I, Price, J L, Yan, Z, et al. (2010) Resting-state functional MRI in depression unmasks increased connectivity between networks via the dorsal nexus. Proceedings of the National Academy of Sciences, 107, 11020–5.Google Scholar
Smith, S E, Lindefors, N, Hurd, Y, et al. (1995) Electroconvulsive shock increases dopamine D1 and D2 receptor mRNA in the nucleus accumbens of the rat. Psychopharmacology, 28, 333–40.Google Scholar
Smith, S E, Sharp, T (1997) Evidence that the enhancement of dopamine function by repeated electroconvulsive shock requires concomitant activation of D1-like and D2-like dopamine receptors. Psychopharmacology, 133, 77–84.Google Scholar
Takamiya, T, Chung, J K, Liang, K-C, et al. (2018) Effect of electroconvulsive therapy on hippocampal and amygdala volumes: systematic review and meta-analysis. British Journal of Psychiatry, 212, 19–26.Google Scholar
Thomann, P A, Wolf, R C, Nolte, H M, et al. (2017) Neuromodulation in response to electroconvulsive therapy in schizophrenia and major depression. Brain Stimulation, 10, 637–44.Google Scholar
Tynan, R J, Weidenhofer, J, Hinwood, M, et al. (2012) A comparative examination of the anti-inflammatory effects of SSRI and SNRI antidepressants on LPS stimulated microglia. Brain, Behavior, and Immunity, 26, 469–79.Google Scholar
UK ECT Group (2003). Efficacy and safety of electroconvulsive therapy in depressive disorders: a systematic review and meta-analysis. Lancet, 361, 799–808.Google Scholar
van Buel, E M, Bosker, F J, van Drunen, J, et al. (2015) Electroconvulsive seizures (ECS) do not prevent LPS-induced behavioral alterations and microglial activation. Journal of Neuroinflammation, 12, 232–41.Google Scholar
Wilkinson, S T, Sanacora, G, Bloch, M H (2017) Hippocampal volume changes following electroconvulsive therapy: a systematic review and meta-analysis. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging, 2, 327–35.Google Scholar
Yatham, L N, Liddle, P F, Lam, R W, et al. (2010) Effect of electroconvulsive therapy on brain 5‑HT2 receptors in major depression. British Journal of Psychiatry, 196, 474–9.Google Scholar
Yildiz, A, Nikodem, M, Vieta, E, et al. (2015) A network meta-analysis on comparative efficacy and all-cause discontinuation of antimanic treatments in acute bipolar mania. Psychological Medicine, 45, 299–317.Google Scholar

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