Neurobiological Mechanisms of Electroconvulsive Therapy: Molecular Perspectives of Brain Stimulation

Abstract

Electroconvulsive therapy (ECT) remains one of the most effective interventions for treatment-resistant psychiatric disorders, particularly major depressive disorder and bipolar disorder. Despite extensive clinical and preclinical investigations, the precise neurobiological mechanisms underlying ECT's therapeutic effects are not fully understood. This review explores the molecular and cellular pathways involved in ECT, emphasizing its impact on neurotrophic signaling, oxidative stress, apoptosis, and neuroplasticity. Evidence suggests that ECT modulates brain-derived neurotrophic factor and other neurotrophic factors, promoting synaptic plasticity and neuronal survival. Additionally, ECT influences the hypothalamic-pituitary-adrenal axis, reduces neuroinflammation, and alters neurotransmitter systems, contributing to its antidepressant effects. Recent findings also highlight the role of mitochondrial function and oxidative stress regulation in ECT-induced neural adaptation. By synthesizing current molecular insights, this review provides a comprehensive perspective on the neurobiological mechanisms of ECT, offering potential directions for future research and therapeutic advancements in brain stimulation.

Keywords: electroconvulsive therapy; neurobiological mechanisms; neuroplasticity; neurotrophic factors; oxidative stress.

Figure 1

Key theories of potential mechanisms of ECT. The neurotransmitter theory (top-left). The cytokine theory (top-right). The receptors theory (bottom-left). The neurotrophic theory (bottom-right).

Figure 2

Conceptual integration of neurobiological mechanisms involved in ECT. Mitochondrial activation increases ATP production and modulates ROS levels, initiating signaling cascades that regulate inflammation (e.g., IL-6, TNF-α), promote neurogenesis, and upregulate neurotrophic factors such as BDNF and VEGF. These processes enhance synaptic plasticity and neurotransmitter balance, contributing to therapeutic efficacy in MDD.