Exploring the effects of erythropoietin treatment on cortical thickness and hippocampal volume in patients with mood disorders undergoing electroconvulsive therapy: A randomized, placebo-controlled trial.

Background: Electroconvulsive therapy (ECT) is a highly effective treatment for severe depression. However, its utilization is limited to the most severely ill patients due to stigma, healthcare provider unfamiliarity, and concerns regarding cognitive side effects. Erythropoietin (EPO) is a promising add-on treatment during ECT due to its potential to increase neuroplasticity and cognition.

Aims: To explore the effects of EPO administration on cortical thickness and hippocampal volumes.

Methods: In a randomized, double-blinded, placebo-controlled trial, we previously investigated the impact of EPO (40,000 IU) versus placebo (saline) infusions on cognitive side effects of unipolar or bipolar depression patients undergoing eight ECT sessions over 2.5 weeks. This cross-sectional magnetic resonance imaging study explores the effect of EPO on cortical thickness and hippocampal volumes 3 days post-ECT in 37 of the EPO trial patients (EPO n = 21; placebo n = 16).

Results: Compared to the placebo group, EPO-treated patients displayed thicker cortex in distributed regions of the right hemisphere, predominantly in the parietal and occipital areas. There were no significant group differences in the hippocampal volumes or prefrontal cortex thickness.

Conclusions: EPO treatment may produce a selective increase in the right-side occipito-parietal cortical thickness. In contrast, the thickness of other cognition-relevant structures was not significantly affected. This aligns with our previously reported finding that EPO has a selective effect on autobiographical memory and associated right-side parietal activity in the absence of changes in global cognition. It remains to be investigated whether longer EPO treatment and follow-up assessment may be necessary for overt structural changes in cognition-relevant brain networks.