Electroconvulsive therapy, changes in immune cell ratios, and their association with seizure quality and clinical outcome in depressed patients

Major Depressive Disorder (MDD) is a major contributor to the global burden of disease. Approximately 30-50% of depressed patients fail to reach remission with standard treatment approaches. Electroconvulsive therapy (ECT) is one of the most effective options for these patients. Its exact therapeutic mechanism remains elusive, and reliable predictors of response are absent in the routine clinical practice. To characterize its mode of action and to facilitate treatment decision-making, we analyzed ECT's acute and chronic effects on various immune cell subsets. For this purpose, blood was withdrawn from depressed patients (n=21) directly before and 15 min after the first and last ECT session, respectively. After isolating peripheral blood mononuclear cells, we investigated defined populations of immune cells and their proportional changes upon ECT treatment using flow cytometry. By these means, we found ECT remitters (R; n=10) and non-remitters (NR; n=11) to differ in their relative proportion of putative immunoregulatory CD56(high)CD16(-/dim) and cytotoxic CD(56dim)CD16(+) natural killer (NK) cells (CD56(high)CD16(-/dim)/CD56(dim)CD16(+) : R=0.064(+/- 0.005), NR=0.047(+/- 0.005), p<0.05; linear mixed models) and thus in their NK cell cytotoxicity. NK cell cytotoxicity was further increased after a single ECT session (before=0.066(+/- 0.005), after=0.045(+/- 0.005), p<0.001) and was associated with ECT quality parameters (maximum sustained coherence: r(2)=0.389, beta=-0.656, p<0.001) and long-term BDI-II rating changes (r(2)=0.459, beta=-0.726, p<0.05; both linear regression analysis). To conclude, particular NK cell subsets seem to be involved in ECT's acute effect and its clinical outcome. Due to the limited number of patients participating in our pilot study, future approaches are required to replicate our findings. (c) 2020 Elsevier B.V. and ECNP. All rights reserved.