Currents of change: Neurobiological mechanisms, effectiveness, and cognitive side-effects of electroconvulsive therapy for depression

Introduction Depression is one of the most common mental health disorders worldwide, contributing significantly to both psychiatric and physical disease burden. Despite the widespread use of antidepressants and psychotherapy as standard treatments, approximately one-third of patients with depression do not experience sufficient relief, leading to prolonged suffering and increased mortality rates. Electroconvulsive therapy (ECT) is one of the most effective treatments for depression, yet its use remains limited due to stigma and a lack of comprehensive understanding. This research addresses the neurobiological working mechanisms, effectiveness, and cognitive side-effects of ECT. The goal is to personalize and improve the use of ECT for treating depression, ultimately supporting informed decision-making and reducing the stigma surrounding this potentially life-saving therapy. Findings The research yielded three primary conclusions. First, regarding the mechanism of ECT, we observed neuroplastic changes, particularly in the hippocampus—a key brain region. ECT also influences the balance between inflammatory markers and neurotrophic factors, substances that promote growth and repair in the brain. These findings offer insights into how ECT facilitates recovery from depression. Second, several factors emerged as predictors of ECT effectiveness. Older age, the presence of psychotic features (or genetic susceptibility to them), a shorter duration of depressive episodes, the absence of a comorbid personality disorder, and lower resistance to antidepressant medication were all predictors of better outcomes. This information can help guide clinicians in determining which patients are most likely to benefit from ECT. Third, cognitive side-effects of ECT, such as memory issues and difficulties with executive functioning, are typically short-lived, with most patients showing significant cognitive improvement within three months. However, the severity of these side-effects varies based on individual factors, including skull thickness, which influences the strength of the electric field in the brain. This highlights the need for a more personalized approach to ECT administration. Furthermore, our findings suggest that the commonly used Mini-Mental State Examination is inadequate for assessing cognitive side-effects, and we advise against its use in this context. Practical Implications The insights gained from these studies have significant implications for clinical practice. First, a better understanding of how ECT works and the evidence supporting its safety may help reduce the stigma associated with the treatment and increase its acceptance. Second, the identification of accessible clinical predictors of ECT outcomes can help reduce uncertainty around the decision to initiate ECT, thereby supporting more personalized and targeted patient selection. Third, the research offers valuable guidance on managing cognitive side-effects, enabling better patient education. While most patients experience only temporary cognitive challenges, some may face longer-lasting difficulties. Communicating this effectively to patients and providing appropriate support, such as cognitive strategy training, are essential steps toward improving patient care. Additionally, personalizing ECT parameters could minimize cognitive side-effects. These findings could lead to improved treatment with ECT. Methodology This dissertation employed a variety of research methods. In collaboration with multiple Dutch institutions, we established the Dutch ECT Consortium (DEC) consisting of 1892 patients with severe depression. Additionally, we conducted genetic research, analyzing the DNA of ECT patients to identify polygenic vulnerabilities associated with treatment outcomes. To explore the neurobiological mechanisms of ECT, we examined brain tissue from patients who had undergone ECT within five years prior to their death. Using MRI scans, we also assessed the electric field strength generated by ECT in the brain and investigated its relationship with effectiveness and side-effects. Conclusion This research advances our understanding of the neurobiological mechanisms, effectiveness, and cognitive side-effects of ECT in the treatment of depression. The findings hold promise for improving clinical decision-making, personalizing treatment, and ultimately enhancing patient outcomes while reducing the stigma surrounding ECT.