Metabolic Mechanisms in Electroconvulsive Therapy for Schizophrenia: Role, Potential and Future Directions

TL;DR

This paper explores how metabolism and immune-endocrine interactions during ECT may help treat schizophrenia, offering new biomarkers and treatment insights.

Contribution

Proposes a novel 'metabolism-immunity-neuroendocrine' hypothesis to explain ECT's antipsychotic effects and compares it with other therapies.

Findings

ECT regulates brain and peripheral metabolism, impacting energy pathways and redox stress.

Key metabolites in energy and immune pathways show potential as schizophrenia biomarkers.

Comparative analysis reveals similarities and differences in metabolic regulation across therapies and disorders.

Abstract

The metabolism of the four major substances—glucose, lipids, amino acids, and nucleotides—constitutes the most prominent metabolic phenotype of schizophrenia. The pathological axis shared by these substances involves energy pathway imbalances, redox stress, immune-inflammatory activation, and abnormalities in neurotransmitter synthesis/degradation. Existing research confirms that key metabolites within these pathways hold potential as biomarkers for diagnosis or progression monitoring. In recent years, electroconvulsive therapy (ECT) has been shown to improve psychotic symptoms while exerting broad regulatory effects on neurogenesis, immune homeostasis, and the hypothalamic–pituitary–target gland axis, though its precise mechanisms remain unclear. Recent studies indicate that ECT treatment can also regulate changes in brain and peripheral metabolism. We propose an integrated “metabolism-immunity-neuroendocrine” hypothesis to systematically elucidate how metabolic reprogramming during ECT treatment cascades sequentially to the immune, neural, and endocrine systems, thereby revealing the molecular basis of its antipsychotic effects. Furthermore, we conduct a comparative analysis of the effects of antipsychotic drugs on the same metabolic network and explore the universality and specificity of metabolic regulation in other physical therapies (such as rTMS, tDCS) and psychiatric disorders like depression and bipolar disorder. This research aims to provide novel biomarkers and intervention targets for the precision diagnosis and treatment of schizophrenia.

Figures