Depressive disorders are associated with increased peripheral blood cell deformability: a cross-sectional case-control study (Mood-Morph)

Abstract

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.

Correlations between proBDNF/p75NTR and inflammatory markers in patients with major depression

“…Consistent with our previous observation, major depressive patients exhibit signi cantly lower percentage of CD45 + lymphocytes and elevated CD4 + CD8 − -CD3 + T cells with decreased CD4 − CD8 + -CD3 + T cells (Yang, Ning, et al 2020). A recent paper reported depressive disorders were associated with increased peripheral blood cell deformability (Walther et al 2022). Moreover, a largest transcriptome-wide association study (TWAS) for postpartum depression con rmed that B cells had a majority of transcriptome-wide signi cant changes, implicating altered B-cell activation and insulin resistance (Walther et al 2022).…”

Immune Cell Deformability in Depressive Disorders: Longitudinal Associations Between Depression, Glucocorticoids and Cell Deformability

“…This observational study used a longitudinal design with a baseline measurement and a one-year follow-up measurement. Cross-sectional results of the study were reported elsewhere (Walther et al, 2022b). Baseline examination of participants took place between October and December 2018, while follow-up examinations were conducted one year later.…”

“…Only recently, using RT-DC, we were able to show that in DD and especially in PDD immune cell deformability is increased as compared to healthy controls (Walther et al, 2022b). Although all major blood cells tended to be more deformable, lymphocytes, monocytes and neutrophils were particularly affected indicating immune cell mechanical changes to occur in DD.…”

“…A related point is the single assessment of the diagnostic groups by clinical interview at T2. Since we intended to capture group differences in cell deformability (Walther et al, 2022b), the clinical diagnostics as well as the cell deformability measurement had to be performed at the same time point in order to avoid possible time effects. However, in a follow-up project, clinical diagnostics will also be performed at two time points together with cell deformability measurement.…”

“…Further, Jasenovec et al (2019) examined children within the autism spectrum identifying those children with more severe symptoms to show impaired erythrocyte deformability. It should be noted here, however, that the current gold standard for measuring cell deformability, namely RT-DC (Kräter et al, 2021; Nawaz et al, 2020; Otto et al, 2015a; Urbanska et al, 2020; Wu et al, 2018), was only used in our landmark study comparing individuals with DD and healthy controls (Walther et al, 2022b).…”