What is it about?
lectroconvulsive therapy, or ECT, is one of the most effective treatments for severe depression that has not improved with standard treatments. However, doctors still cannot reliably predict which patients are most likely to benefit from it. This systematic review looked at whether “epigenetic” changes could help explain why some people respond to ECT and others do not. Epigenetics refers to chemical changes that affect how genes are switched on or off, without changing the DNA code itself. These changes may help explain how life experiences, stress, illness, and treatment interact with biology. This review examined studies of people with treatment-resistant major depression who received ECT and had epigenetic markers measured. Eleven studies were included, covering 498 patients. The review found 31 promising epigenetic markers linked to treatment response. Most studies focused on DNA methylation, a common epigenetic process, and microRNAs, small molecules that help regulate gene activity. These markers were related to brain plasticity, stress regulation, inflammation, immune activity, and other pathways relevant to depression and recovery. The findings suggest that epigenetic markers may one day help clinicians better understand and predict response to ECT, but the evidence is still early. Larger and more standardized studies are needed before these markers can be used in routine clinical practice.
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Why is it important?
This work is important because it brings together emerging evidence on how ECT may work at a molecular level in treatment-resistant depression. Although ECT is highly effective, its biological mechanisms remain incompletely understood, and clinical practice still lacks reliable tools to predict who will respond. The review is timely because precision psychiatry is increasingly focused on moving beyond trial-and-error treatment decisions. By identifying 31 candidate epigenetic biomarkers, this article highlights a possible path toward more personalized use of ECT. These findings could support future research into blood-based biomarkers, patient stratification, and individualized treatment planning.
Perspectives
My perspective is that ECT should not be viewed only through the lens of clinical outcome but also as a window into the biology of severe depression and recovery. Epigenetic research offers a promising way to connect environmental stress, gene regulation, brain plasticity, and treatment response. Although the field is still at an early stage, I believe this approach may help reduce uncertainty for patients and clinicians, improve treatment selection, and contribute to a more personalized model of psychiatric care.
Nikolaos Statharakos
Aristotle University of Thessaloniki
Read the Original
This page is a summary of: Towards Precision ECT: A systematic review of epigenetic biomarkers in treatment-resistant depression, Psychiatriki, August 2025, Hellenic Psychiatric Association,
DOI: 10.22365/jpsych.2025.021.
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