Mechanism underlying the therapeutic effects of electroconvulsive therapy (ECT) on depression

Electroconvulsive therapy (ECT) is used to treat drug-resistant depressive disorders. The results of studies on the mechanism underlying the effective ness of ECT on depression are still controversial. ECT stimulus is usually larger than the threshold of induction of seizures and activation of whole- brain is believed to be necessary to produce therapeutic effects. A single ECT session induces alterations of the electroencephalogram (EEG) including initial epileptic discharges, then slow waves, and finally flattened EEG. Repeated ECT results in an increasing number of slower waves in the EEG for as long as a month. ECT-induced changes in various neurotransmitter system s have also been reported. Serotonin (5-hydroxytryptamine, 5-HT) is one of the most important neurotransmitters involved in depressive illness, and EC T alters several 5-HT-receptor subtypes in the central nervous system. 5-HT 1A receptors in post-synaptic neurons are sensitized by repeated ECT, but t hose in pre-synaptic neurons (auto-receptors) are not changed. In addition, our electrophysiological studies have shown that ECT increases sensitivity to 5-HT of 5-HT3 receptors in the hippocampus, resulting in an increase in release of neurotransmitters such as glutamate and gamma-aminobutyric acid . In contrast, ECT decreases the auto-receptor functions in noradrenergic a nd dopaminergic neurons in the locus coeruleus and substantia nigra, respec tively, resulting in an increase in release of noradrenaline and dopamine. In conclusion, 5-HT1A-receptor sensitization may be important for explainin g the effectiveness of ECT, as this change induces a decrease in the number of 5-HT2A receptors that are elevated in depressive patients. Facilitation of neurotransmitter releases due to 5-HT3-receptor sensitization by ECT ma y also play an important role in effective treatment of depressive patients refractory to therapeutic drugs.