Clinical and biological markers of electroconvulsive therapy effectiveness: a narrative review

Electroconvulsive therapy (ECT) is the most effective treatment for several particularly severe or pharmacotherapy-resistant psychiatric disorders, and a growing number of studies have investigated factors influencing the effectiveness of ECT. The objective of this article is to review the current evidence on clinical and biological markers potentially related to response to ECT and to outline perspectives for future research. In depressive disorders, the presence of clinical characteristics such as higher age, psychotic and psychomotor symptoms, and the absence of comorbid personality disorders are associated with a particularly good response to ECT. However, these clinical factors alone explain only a part of the variance of treatment outcome. Biomarkers at the genetic/epigenetic, immune inflammatory, and brain imaging levels are now providing promising and, in part, converging findings on both the mechanism of action and predictors of response to ECT. Taken together, these findings suggest a close relationship between specific clinical symptoms, the immune inflammatory, and neuroplastic mechanisms of ECT. While genetic studies consistently indicate a higher genetic risk load in patients referred for ECT, findings regarding the predictive value of polygenic risk scores and also epigenetic markers for ECT response remain inconsistent. In the future, combining clinical features and biomarkers could help define subgroups of psychiatric disorders with distinct pathophysiology and reliably predict treatment outcomes at the individual patient level. For now, it may be assumed that different and possibly age-dependent prototypical forms of depressive disorders exist, which are characterized by specific clinical (psychotic and psychomotor symptoms) and inflammatory markers (higher levels of IL-6 and CRP) and show a differential response to treatment modalities.