[ECT: from neuronal plasticity to mechanisms underlying antidepressant medication effect]

Encephale. 2007 Sep;33(4 Pt 1):572-8. doi: 10.1016/s0013-7006(07)92055-2.
[Article in French]

Abstract

Introduction: Electroconvulsive therapy (ECT) is one of the most effective treatments for depression. Although it has been used for over 60 years, the basis for its therapeutic effect is still unknown. Structural plasticity within the nervous system such as neurogenesis or mossy fiber sprouting could be involved in the mechanisms underlying the antidepressant effect of several pharmacological antidepressants. But what is the mechanism underlying ECT?

Literature findings: Several methodological issues using magnetic resonance spectroscopy for humans and rats found changes in neuronal metabolism during ECT. The levels of N-Acetyl-Aspartate, an amino acid exclusively located in neurons, are increased after ECT; choline, which is believed to represent membrane turn-over, increases as well. These results are in good agreement with ECT induced structural plasticity. Electroconvulsive seizures (ECS), an animal model of ECT, can enhance neurogenesis, particularly in the hippocampal dentate gyrus. A series of seizures increases neurogenesis more than a single shock. In the glucocorticoid paradigm of depression, ECS can increase hippocampal neurogenesis. This suggests that induction of neurogenesis might be implicated in the antidepressant mechanism of ECT.

Discussion: As suggested by previous studies, Brain Derived Neurotrophic Factor (BDNF) is supposed to play a critical role in the action of antidepressants through neuronal plasticity. ECS increases the expression of BDNF. The BDNF gene has four differentially regulated promoters that generate four transcript forms. Studying the regulation of these transcript forms by diverse classes of antidepressant therapeutics, including ECS, suggests that diverse signalling mechanisms may be recruited to regulate BDNF transcripts. Moreover, for ECS, these signalling mechanisms seem to differ from those recruited by excitotoxic cell death phenomena, such as neuronal damage or epileptic seizure models.

Conclusion: These results indicate the participation of neuronal plasticity to help account for the antidepressant effect of ECT. However, this relationship is currently not clearly defined, particularly in terms of causality, and will require future studies to unravel it.

Publication types

  • English Abstract
  • Review

MeSH terms

  • Antidepressive Agents / pharmacology*
  • Antidepressive Agents / therapeutic use*
  • Aspartic Acid / analogs & derivatives
  • Aspartic Acid / metabolism
  • Brain / drug effects*
  • Brain / physiopathology*
  • Brain-Derived Neurotrophic Factor / drug effects
  • Brain-Derived Neurotrophic Factor / metabolism
  • Choline / metabolism
  • Depressive Disorder, Major / physiopathology*
  • Depressive Disorder, Major / therapy*
  • Electroconvulsive Therapy / methods*
  • Exons / drug effects
  • Humans
  • Neuronal Plasticity / drug effects*

Substances

  • Antidepressive Agents
  • Brain-Derived Neurotrophic Factor
  • Aspartic Acid
  • N-acetylaspartate
  • Choline