Biology may influence who benefits from ECT treatment

ECT is considered one of the most effective treatments for major depressive disorder, yet it is often offered only after other interventions have failed.

The procedure uses a controlled electrical current to induce a brief, medically supervised seizure while the patient is under anesthesia, typically when medication or psychotherapy has not worked or is unsuitable.

An international research team led by scientists at the University of Bergen now offers new insight into why some patients benefit from ECT while others do not.

Largest epigenetic study of ECT so far

The study examined epigenetic patterns and immune‑related markers in blood samples from nearly 100 patients in Norway and Germany. It is the largest epigenetic investigation of ECT to date.

The most striking finding was that patients who later responded well to ECT already showed distinct biological differences in their DNA before treatment began, compared with those who did not respond. The ECT treatment itself did not produce measurable changes in gene expression.

“Patients who responded well stood out based on specific biomarkers,” says Professor Stéphanie Le Hellard.

Radiologist and co‑author Leif Oltedal adds that these biomarkers may also reflect differences in brain plasticity — the brain’s ability to form new neural connections.

“We believe ECT works by disrupting rigid networks in the brain and making it more flexible,” he explains. 

Potential for more precise treatment

Clinicians currently have few objective tools to guide treatment decisions for patients with severe depression. The researchers say their findings could help pave the way for more targeted, personalized approaches.

“The lack of such tools has contributed to long periods of trial and error for patients with serious illness,” Le Hellard notes.

Stigma and the need for better understanding

Despite its effectiveness, the treatment still carries significant stigma. 

“Today, ECT is a highly controlled medical procedure with close patient monitoring,” Le Hellard emphasizes. She adds that reducing stigma requires more than reassurance — it requires stronger scientific understanding and clearer communication about why the treatment works for some patients but not others.

Strengthening the biological knowledge base, she argues, is not only a scientific goal but also a clinical and ethical responsibility. 

Looking ahead

The researchers hope their findings will contribute to a more personalized psychiatry. Oltedal notes that a future scenario where a simple blood test could help determine the best treatment for each patient would be a major step forward. 

The next phase will likely involve joining an international initiative to collect and analyze blood samples from ECT patients on a larger scale.

The team stresses that the results are preliminary and must be confirmed in larger studies, though Oltedal finds it encouraging that the findings were replicated in two independent datasets from Norway and Germany.

Reference: https://www.nature.com/articles/s41398-025-03772-y