Cellular immune phenotype of major depressive disorder – findings from the EMBARC study

OBJECTIVES: Major depressive disorder (MDD) is associated with immune dysfunction. This study aimed to characterize the cellular immunophenotypes that may underpin immune dysregulation in MDD. METHODS: Peripheral blood mononuclear cell (PBMC) samples at baseline from participants with MDD from the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study were included. A panel of 33 antibodies was analyzed using mass cytometry to compare the immune cell abundance and marker expression profiles between participants with mild and moderate/severe depression. Mass cytometry data were investigated using (1) Uniform Manifold Approximation and Projection for Dimension Reduction (UMAP), (2) FlowSOM (self-organizing maps) for clustering, and (3) Significance Analysis of Microarrays (SAM) for statistical analyzes. RESULTS: FlowSOM identified 8 clusters of distinct cell types. The abundance of cytotoxic T, NK, NK T, and Naïve B cells was significantly lower in participants with moderate/severe depression compared to mild depression. NKT cells had significantly lower CD56 and CD16 expression in patients with moderate/severe depression compared to patients with mild depression. CONCLUSION: Our observations provide evidence for alterations in B, NKT, and NK cell abundance and their cell surface markers in moderate/severe depression. Further investigations into immune cell dysfunction in moderate/severe depression are necessary.