Alterations in the Serum Proteome Following Electroconvulsive Therapy for a Major Depressive Episode: A Longitudinal Multicenter Study

BACKGROUND
Electroconvulsive therapy (ECT) is the most effective treatment for severe depression, but the biological changes induced by ECT remain poorly understood.

METHODS
This study investigated alterations in blood serum proteins in 309 patients admitted to ECT for a major depressive episode. We analyzed 201 proteins in samples collected at three time-points: just before the first ECT treatment session (T0), within 30 minutes after the first ECT session (T1), and just before the sixth ECT session (T2).

RESULTS
Using statistical models to account for repeated sampling, we identified 152 and 70 significantly (<5% false discovery rate) altered proteins at T1 and T2, respectively. The most pronounced alterations at T1 were transient increased levels of prolactin, myoglobin, and kallikrein-6. However, most proteins had decreased levels at T1, with the largest effects observed for pro-epidermal growth factor, proto-oncogene tyrosine-protein kinase Src, tumor necrosis factor ligand superfamily member 14, sulfotransferase 1A1, early activation antigen CD69, and CD40 ligand. The change of several acutely altered proteins correlated with electric current and pulse frequency in a dose-response-like manner. Over a five-session course of ECT, some acutely altered levels were sustained while others increased, e.g., serine protease 8 and chitinase-3-like protein 1. None of the studied protein biomarkers were associated with clinical response to ECT. CONCLUSIONS We report experimental data on alterations in the circulating proteome triggered by ECT in a clinical setting. The findings implicate hormonal signaling, the immune system, apoptotic processes, and more. None of the findings were associated with clinical response to ECT.