Biomarkers for Antidepressant Efficacy of Electroconvulsive Therapy: An Exploratory Cerebrospinal Fluid Study

Abstract

Background: No candidate biomarkers based on cerebrospinal fluid (CSF) have been identified as prognostic factors in patients with major depression treated with electroconvulsive therapy (ECT), yet. Method: Following different underlying hypotheses, we analysed baseline CSF levels of markers of neurodegeneration (tau proteins, β-amyloids and neurogranin), elements of the innate immune system (interleukin [IL]-6, neopterin, soluble CD14, soluble CD163, migration inhibitory factor and monocyte chemotactic protein 1), endocannabinoids, sphingolipids and Klotho before ECT in patients with depression (n = 12) to identify possible correlations with the clinical antidepressant response to ECT. Results: Correlation with the reduction of the depressive symptoms could be observed especially for markers of neurodegeneration and elements of the innate immune system. Differences for CSF levels of several markers were found between the groups of responders and non-responders at the trend level. Limitations: The sample size is small and the ­distribution of responders and non-responders is uneven. Conclusions: It is this first study on CSF biomarkers for antidepressant efficacy of ECT warrants further research regarding the mechanism of ECT and personalized antidepressant therapy.

Electroconvulsive therapy, depression severity and mortality: Data from the Danish National Patient Registry

“…This was contrary to our hypothesis, but appears to be a consistent finding in register-based ECT studies (Avery and Winokur, 1976; Munk-Olsen et al, 2007; Philibert et al, 1995). It may be due to confounding from selection of healthier patients for ECT (Bharadwaj and Grover, 2007), but could, in theory, be causally mediated through effects on disease mechanisms (Avery and Winokur, 1976; Kranaster et al, 2019).…”

Mental Illness and Amyloid: A Scoping Review of Scientific Evidence over the Last 10 Years (2011 to 2021)

“…Studies analysing amyloid in response to therapeutic effects (of drugs or electroconvulsive therapies) further suggest the role of amyloid not only as a biomarker but also as a pathogenic element [27][28][29]39]; increment of Aβ peptides in plasma after electroconvulsive therapy suggests the possible role of amyloid as a marker of response to therapy. In particular, in a study by Kranaster and collaborators [29], tau protein, its phosphorylated isoform, Aβ40, and neurogranin were correlated with any form of therapeutic effect. Another study by Kranaster et al [28] observed a specific antidepressant mechanism not based on a general increase of Aβ, but on the specifically increment of Aβ42, the isoform with the highest amyloidogenic potential.…”

“…In three of these studies [27][28][29], the response to a treatment was considered. Clarke et al [27] observed an alteration in Aβ40 and p-tau in patients with major depressive disorders (MDD) receiving antipsychotic drugs, compared with those not receiving them.…”

“…Clarke et al [27] observed an alteration in Aβ40 and p-tau in patients with major depressive disorders (MDD) receiving antipsychotic drugs, compared with those not receiving them. Kranaster et al [28] observed a correlation between the response to electroconvulsive therapy (ECT) and the increment of Aβ42, whereas Kranaster et al [29] explored the involvement of CSF levels of p-tau, t-tau, and Aβ40 in reduction of depressive symptoms after ECT.…”

Understanding the mechanisms of treatment response in depression, focus on electro-convulsive therapy

“…Following up on a previous publication exploring how cerebrospinal fluid (CSF) biomarkers correlate with symptom improvement in ECT [8], Kranaster et al, [6] here address the important issue how parameters used to monitor the quality of ECT (similar in principle to therapeutic drug monitoring for pharmacotherapy) correlate with such biomarkers. Specifically, they evaluate how a validated seizure quality index (SQI), based on the extent of several ictal parameters of the seizure that can be assessed at bedside and predicts treatment outcome [9], correlates with the same CSF biomarkers.…”