Cell deformability of peripheral blood mononuclear cells is reduced in individuals with major depressive disorder

Major depressive disorder (MDD) is a complex mental disorder with a pathophysiology that remains only partly understood and involves, among other factors, alterations in immune system function. One of the main risk factors for mental disorders, in particular trauma-spectrum disorders like depression and complex PTSD, is childhood maltreatment (CM). However, their impact on the biophysical properties of immune cells remains unexplored. This study investigated PBMC deformability in 26 individuals diagnosed with MDD and 28 healthy controls. CM was assessed using the Childhood Trauma Questionnaire (CTQ). A microfluidic deformability assay was employed to assess immune cell deformability, with cell viability controlled in PBMC samples before measurement using trypan blue staining.PBMCs from individuals with MDD exhibited significantly reduced deformability compared to those from healthy controls, indicating increased cellular stiffness. CM was not significantly associated with PBMC deformability, suggesting that the MDD phenotype itself, with its multiple potential etiological causes, plays a more crucial role in cell stiffness than any single risk factor. These findings suggest that immune cell stiffness is elevated in MDD when assessed in isolated PBMCs, contrasting with previous studies that reported increased deformability measured in whole blood.Based on our working hypothesis, we interpret our results as indicative of damage to intracellular structures, including the cytoskeleton and cell membrane, likely due to increased exposure to free radicals from chronic or excessive stress. This may compromise membrane integrity and alter fatty acid composition. Functionally, these findings could enhance the biophysical understanding of impaired wound healing and other immunological dysfunctions commonly observed in MDD.