Abstract
Major depressive disorder (MDD) is a highly prevalent and disabling condition. As such, understanding the causes of and treatment options for MDD is critical. Electroconvulsive therapy (ECT) remains the gold standard depression treatment, but the molecular mechanisms that underlie its effects are still largely unknown. One such explanation hinges on the immuno-inflammatory correlates of ECT treatment, given mounting evidence supporting the inflammatory hypothesis of depression. This review aims to provide an overview of the suggested immunomodulatory effects of ECT and the predictive value of immune biomarkers in relation to treatment outcomes and side effects. We conducted a preregistered, systematic literature search utilizing MEDLINE (PubMed), Embase (Elsevier), and PsycINFO (EBSCO) databases. We employed keywords related to MDD, ECT, gut microbiome, and the immune system. We only included human subjects research published between 1985 and January 13, 2021. Twenty-six unique studies were included in our analyses. Findings indicate a proinflammatory profile associated with MDD, with immune biomarkers exhibiting acute and chronic changes following ECT. Consistently, lower baseline interleukin 6 levels and higher C-reactive protein levels are correlated with a greater reduction in depressive symptoms following ECT. Furthermore, included studies emphasize the predictive value of peripheral immune changes, specifically interleukin 6 and tumor necrosis factor α, on cognitive outcomes following ECT. Given these results, further exploration of the potential roles of immunomodulatory effects on ECT treatment outcomes, as well as adverse cognitive side effects, is indicated.