Summary: Researchers have identified a relationship between depressive disorders and altered mechanical properties of blood cells.
Source: TUD
Depression commonly presents with loss of interest, persistent low mood, reduced motivation and heightened fatigue. In Germany, roughly 5% of the population are affected, making it a major public health concern.
Alongside psychological symptoms, depressive disorders frequently involve biological changes such as low-grade chronic inflammation and increased glucocorticoid release. These physiological alterations can affect cell structure and function.
A new study, published in Translational Psychiatry, brings fresh insight by linking depressive disorders to mechanical changes in peripheral blood cells. The research team included scientists from Technische Universität Dresden, the University of Zurich, and the Max Planck Institutes for the Science of Light and for Physics and Medicine Erlangen.
The researchers carried out a cross-sectional case-control study using image-based morpho-rheological analysis of unmanipulated blood samples with real-time deformability cytometry (RT-DC). This technique measures how cells deform under flow, offering direct information about cell mechanical properties without extensive manipulation.
The study enrolled 69 pre-screened individuals at high risk for depressive disorders and 70 matched healthy controls. All participants underwent standardized clinical assessment using the Composite International Diagnostic Interview to establish lifetime and 12-month psychiatric diagnoses.
Using deep learning to analyze over 16 million blood cell images, the team automatically classified major blood cell types and quantified morpho-rheological parameters, including cell size and deformability, for each individual cell.
The core finding was that peripheral blood cells from individuals with depressive disorders were generally more deformable than those from control subjects, while average cell size showed no consistent differences. This indicates altered mechanical properties rather than changes in cell volume.
More specifically, people with lifetime persistent depressive disorder—defined by symptoms lasting more than two years—showed notably increased deformability in monocytes and neutrophils. In participants with persistent depressive disorder during the past 12 months, red blood cells (erythrocytes) also displayed increased deformability. Lymphocytes were more deformable in those with a current major depressive episode.
Although multiple blood cell types showed a trend toward greater deformability, lymphocytes, monocytes and neutrophils were the most affected. These immune cells play key roles in inflammation and host defense, suggesting that altered cell mechanics in immune populations could contribute to or reflect a sustained inflammatory state in depressive disorders.
Identifying increased blood cell deformability as a pathomechanism linked to depressive disorders may open new therapeutic avenues. Interventions that restore normal cell mechanics could potentially improve dysfunctional cell behavior and modulate chronic immune activation associated with depression.
For first author Dr. Andreas Walther, who conducted the study at the Chair of Biopsychology at TU Dresden and now works at the Institute of Clinical Psychology and Psychotherapy at the University of Zurich, the findings support a comprehensive treatment strategy:
“We are pursuing research on pharmacological approaches to correct dysfunctional biology alongside psychological therapies to address dysfunctional cognitive and emotional processes. I believe only a holistic approach can fully understand and effectively treat this complex disorder, and ultimately help prevent suffering.”
About this depression research news
Author: Anne-Stephanie Vetter
Source: TUD
Contact: Anne-Stephanie Vetter – TUD
Image: The image is in the public domain
Original Research: Open access — “Depressive disorders are associated with increased peripheral blood cell deformability: a cross-sectional case-control study (Mood-Morph)” by Andreas Walther et al., Translational Psychiatry
Abstract
Depressive disorders are associated with increased peripheral blood cell deformability: a cross-sectional case-control study (Mood-Morph)
Chronic low-grade inflammation and elevated glucocorticoid output are established pathophysiological features of depressive disorders. Both processes can alter cytoskeletal organization, membrane mechanics and cellular function, implying that morpho-rheological properties such as cell deformability may be affected in depression.
In this case-control study, unmanipulated peripheral blood samples were analyzed by real-time deformability cytometry. Sixty-nine pre-screened individuals at high risk for depressive disorders and 70 matched healthy controls underwent clinical evaluation with the Composite International Diagnostic Interview to determine lifetime and 12-month diagnoses.
Deep learning methods classified major blood cell types from more than 16 million images and quantified parameters including cell size and deformability for each cell. Peripheral blood cells from participants with depressive disorders were consistently more deformable than those from controls, whereas cell size did not differ.
Lifetime persistent depressive disorder correlated with increased deformability in monocytes and neutrophils; 12-month persistent depressive disorder showed increased deformability of erythrocytes; and lymphocyte deformability was elevated in 12-month major depressive disorder. After correction for multiple testing, associations with lifetime persistent depressive disorder remained most robust.
This study is the first to analyze whole blood cell morpho-rheological properties in depression and highlights increased deformability—especially in immune cells—as a correlate of depressive disorders. These mechanical alterations may reflect or contribute to a sustained immune response and offer potential targets for future therapeutic strategies.