Molecular Biomarkers of Electroconvulsive Therapy Effects and Clinical Response: Understanding the Present to Shape the Future

Abstract

Electroconvulsive therapy (ECT) represents an effective intervention for treatment-resistant depression (TRD). One priority of this research field is the clarification of ECT response mechanisms and the identification of biomarkers predicting its outcomes. We propose an overview of the molecular studies on ECT, concerning its course and outcome prediction, including also animal studies on electroconvulsive seizures (ECS), an experimental analogue of ECT. Most of these investigations underlie biological systems related to major depressive disorder (MDD), such as the neurotrophic and inflammatory/immune ones, indicating effects of ECT on these processes. Studies about neurotrophins, like the brain-derived neurotrophic factor (BDNF) and the vascular endothelial growth factor (VEGF), have shown evidence concerning ECT neurotrophic effects. The inflammatory/immune system has also been studied, suggesting an acute stress reaction following an ECT session. However, at the end of the treatment, ECT produces a reduction in inflammatory-associated biomarkers such as cortisol, TNF-alpha and interleukin 6. Other biological systems, including the monoaminergic and the endocrine, have been sparsely investigated. Despite some promising results, limitations exist. Most of the studies are concentrated on one or few markers and many studies are relatively old, with small sample sizes and methodological biases. Expression studies on gene transcripts and microRNAs are rare and genetic studies are sparse. To date, no conclusive evidence regarding ECT molecular markers has been reached; however, the future may be just around the corner.

Peripheral proteomic changes after electroconvulsive seizures in a rodent model of non-response to chronic fluoxetine

“…Novel pharmacological approaches including ketamine are also gaining attention, however they yet did not present a superiority of effect compared to electroconvulsive therapy ( Veraart et al, 2021 ). Despite the frequent and widespread use of ECT, possible cognitive impairments and other adverse effects were described and its molecular mechanisms underlying its efficacy remains largely unclear [for review ( Maffioletti et al, 2021 )]. Thus, before engaging into ECT treatment, the search for predictors of ECT response in animal models of anxiety/depression would benefit to patients with MDD.…”

“…Expression studies on gene transcripts and microRNAs are rare and genetic studies are sparse. To date, no conclusive evidence regarding ECT molecular markers of clinical response has been reached ( Maffioletti et al, 2021 ).…”

“…Several clinical studies tried to identify novel biomarkers predicting ECT outcomes and responses to targeted treatments [for review, ( Maffioletti et al, 2021 )]. Thus, ECT modulates the expression of 10 and ≈40 proteins in the blood of patients after either acute or chronic ECT, respectively ( Stelzhammer et al, 2013 ).…”

“…Moreover, AD treatment adjuncts with chronic ECT changes proteins profile compared to patients receiving only ECT. However, most of the studies are concentrated on one or few markers and many studies are relatively old, with small sample sizes and methodological biases ( Maffioletti et al, 2021 ).…”

Thorough consideration of electroconvulsive therapy (ECT) in treatment-resistant psychiatric disorders

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The article by Howes et al [1] presents a valuable framework and broad access to the topic of treatment-resistant disorders in psychiatry and deserves to be read by both researchers and clinicians. Nevertheless, we would like to comment on the too short and maybe even misleading passage on electroconvulsive therapy (ECT).The relative importance of ECT for the treatment of the most severe and treatment-resistant disorders in psychiatry and its potential for a better understanding of the neurobiology of treatment response [2,3] should merit more than only three sentences in an otherwise comprehensive overview. From a practitioner's viewpoint, ECT is much more than an approved therapy for "treatment-resistant depression and mania" [4].

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