RESUMEN
Cell deformability of all major blood cell types is increased in depressive disorders (DD). Furthermore, impaired glucocorticoid secretion is associated with DD, as well as depressive symptoms in general and known to alter cell mechanical properties. Nevertheless, there are no longitudinal studies examining accumulated glucocorticoid output and depressive symptoms regarding cell deformability. The aim of the present study was to investigate, whether depressive symptoms predict cell deformability one year later and whether accumulated hair glucocorticoids mediate this relationship. In 136 individuals (nfemale = 100; Mage = 46.72, SD = 11.28; age range = 20-65), depressive symptoms (PHQ-9) and hair glucocorticoids (cortisol and cortisone) were measured at time point one (T1), while one year later (T2) both depressive symptoms and hair glucocorticoids were reassessed. Additionally, cell deformability of peripheral blood cells was assessed at T2. Depression severity at T1 predicted higher cell deformability in monocytes and lymphocytes at T2. Accumulated hair cortisol and cortisone concentrations from T1 and T2 were not associated with higher cell deformability and further did not mediate the relationship between depressive symptoms and cell deformability. Elevated depressive symptomatology in a population based sample is longitudinally associated with higher immune cell deformability, while long-term integrated glucocorticoid levels seem not to be implicated in the underlying mechanism.
RESUMEN
Real-time deformability cytometry (RT-DC) is an established method that quantifies features like size, shape, and stiffness for whole cell populations on a single-cell level in real-time. A lookup table (LUT) disentangles the experimentally derived steady-state cell deformation and the projected area to extract the cell stiffness in the form of the Young's modulus. So far, two lookup tables exist but are limited to simple linear material models and cylindrical channel geometries. Here, we present two new lookup tables for RT-DC based on a neo-Hookean hyperelastic material numerically derived by simulations based on the finite element method in square and cylindrical channel geometries. At the same time, we quantify the influence of the shear-thinning behavior of the surrounding medium on the stationary deformation of cells in RT-DC and discuss the applicability and impact of the proposed LUTs regarding past and future RT-DC data analysis. Additionally, we provide insights about the cell strain and stresses, as well as the influence resulting from the rotational symmetric assumption on the cell deformation and volume estimation. The new lookup tables and the numerical cell shapes are made freely available.
RESUMEN
Pathophysiological landmarks of depressive disorders are chronic low-grade inflammation and elevated glucocorticoid output. Both can potentially interfere with cytoskeleton organization, cell membrane bending and cell function, suggesting altered cell morpho-rheological properties like cell deformability and other cell mechanical features in depressive disorders. We performed a cross-sectional case-control study using the image-based morpho-rheological characterization of unmanipulated blood samples facilitating real-time deformability cytometry (RT-DC). Sixty-nine pre-screened individuals at high risk for depressive disorders and 70 matched healthy controls were included and clinically evaluated by Composite International Diagnostic Interview leading to lifetime and 12-month diagnoses. Facilitating deep learning on blood cell images, major blood cell types were classified and morpho-rheological parameters such as cell size and cell deformability of every individual cell was quantified. We found peripheral blood cells to be more deformable in patients with depressive disorders compared to controls, while cell size was not affected. Lifetime persistent depressive disorder was associated with increased cell deformability in monocytes and neutrophils, while in 12-month persistent depressive disorder erythrocytes deformed more. Lymphocytes were more deformable in 12-month major depressive disorder, while for lifetime major depressive disorder no differences could be identified. After correction for multiple testing, only associations for lifetime persistent depressive disorder remained significant. This is the first study analyzing morpho-rheological properties of entire blood cells and highlighting depressive disorders and in particular persistent depressive disorders to be associated with increased blood cell deformability. While all major blood cells tend to be more deformable, lymphocytes, monocytes, and neutrophils are mostly affected. This indicates that immune cell mechanical changes occur in depressive disorders, which might be predictive of persistent immune response.