Title: Depressive disorders are associated with increased peripheral blood cell deformability: a cross-sectional case-control study (Mood-Morph)
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
Fig. 1. Real-time deformability cytometry and subsequent AI-based classification of blood cells.
A A schematic illustration of an RT-DC measurement chip is shown. Whole blood was resuspended in measurement buffer (CellCarrierB), drawn in a syringe, and connected to the sample inlet. CellCarrierB was used as a sheath fluid within a second syringe and the sample and sheath were flushed through the chip at a ratio of flow rates of 1:3 under constant flow (0.06 µL/s). The chip was mounted to an inverted microscope and an image of every cell was recorded at the end of a 600 µm long constriction cannel. B Using ShapeOut, an open-source software tool, data were plotted. The dot-plot shows a measurement of 38,517 blood cells plotted in cell size (projected area [µm²]) and cell deformability. For better representation, the ratio of leukocytes (IV, Vi-iii) to erythrocytes and thrombocytes (I–III) is artificially increased. In order to identify the different blood cell types, the images were imported to AIDeveloper an open-source software tool to train, evaluate, and apply neural networks for image classification. A neural net based on the LeNet5 architecture, readily trained for the classification of blood cells, was loaded into AID and used to classify I = thrombocytes, II = erythrocytes, III = erythrocyte doublets, IV = lymphocytes, Vi = eosinophils, Vii = neutrophils, and Viii = monocytes. Finally, the mean values for cell deformability and cell size were extracted for every cell type individually.
Emotional disorders may cause physical illness.