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Neurotransmitters and Electroconvulsive Therapy

Baldinger, Pia MD*; Lotan, Amit MD; Frey, Richard MD*; Kasper, Siegfried MD*; Lerer, Bernard MD; Lanzenberger, Rupert MD*

doi: 10.1097/YCT.0000000000000138
Invited Reviews

Objectives Electroconvulsive therapy (ECT) is a well-established effective treatment strategy in treatment-refractory depression. However, despite ECT’s widespread use, the exact neurobiological mechanisms underlying its efficacy are not fully understood. Over the past 3 decades, extensive work in rodents, primates, and humans has begun to delineate the impact of electroconvulsive seizures (ECS) and ECT on neurotransmission systems commonly implicated in depression. In the current review, we will focus on two major biogenic amine systems, namely serotonin and dopamine.

Methods The database of PubMed was searched for preclinical studies describing the effects of ECS on the serotonergic and dopaminergic system using behavioral sensitization paradigms, in vivo brain microdialysis, messenger RNA and protein expression, electrophysiology, and positron emission tomography. Additionally, human data describing ECT’s effects on neurotransmitter turnover, receptor binding, and functional imaging were reviewed together with relevant genetic association studies.

Results Literature research resulted in 40 published original studies related to ECS/ECT and the serotonergic system, whereby only three were studies in humans. Regarding dopamine, 15 preclinical and 12 human studies were found in PubMed database.

Conclusions Converging data obtained from genetic and imaging studies in humans have corroborated many of the earlier preclinical and clinical findings relating to enhancement of serotonergic neurotransmission and activation of the mesocorticolimbic dopamine system after ECS/ECT. Moreover, it seems that these effects are evident at various levels, including neurotransmitter release, receptor binding, and overall neurotransmission. Future studies combining convergent modalities could enhance our understanding of the mechanisms underlying ECT’s profound antidepressant effect and would support the development of better pharmacological and somatic treatment approaches for refractory depression.

From the *Department of Psychiatry and Psychotherapy, Medical University of Vienna, Austria and †Biological Psychiatry Laboratory at Hadassah, Hebrew University Medical Center, Jerusalem, Israel.

Received for publication February 11, 2014; accepted March 17, 2014.

Reprints: Rupert Lanzenberger, MD, Department of Psychiatry and Psychotherapy, Medical University of Vienna, Währinger Gürtel 18–20, A-1090 Vienna, Austria (e-mail:

Pia Baldinger and Amit Lotan contributed equally to this work.

Without any relevance to this work, S. Kasper declares that he has received grant/research support from Eli Lilly, Lundbeck A/S, Bristol-Myers Squibb, Servier, Sepracor, GlaxoSmithKline, Organon, Dr. Willmar Schwabe GmbH & Co. KG, and has served as a consultant or on advisory boards for AstraZeneca, Austrian Sick Found, Bristol-Myers Squibb, German Research Foundation (DFG), GlaxoSmithKline, Eli Lily, Lundbeck A/S, Pfizer, Organon, Sepracor, Janssen, and Novartis and has served on speakers’ bureaus for AstraZeneca, Eli Lilly, Lundbeck A/S, Servier, Sepracor, and Janssen. R. Lanzenberger received travel grants and conference speaker honoraria from AstraZeneca, Lundbeck A/S, and Roche Austria GmbH. R. Frey declares that he has received grants and research support from Bristol-Myers Squibb, AstraZeneca, Sandoz, Eli Lilly, and Janssen. P. Baldinger received travel grants from Roche Austria GmbH and AOP Orphan Pharmaceuticals AG. B. Lerer has received grants for studies unrelated to this work from the Israel Ministry of Science and Technology, the Israel Ministry of Economics, Trade and Industry, the Israel Science Foundation, Israel Academy of Sciences, the European Union, St Jude Medical, and Janssen Pharmaceuticals and has served as a paid consultant to St Jude Medical, Anima Scan Ltd, and Taliaz Diagnostics on unrelated projects.

© 2014 by Lippincott Williams & Wilkins