Loss of interest, joylessness, lack of drive and increased fatigability – all these complaints are among the main symptoms of depression, a mental illness affecting an estimated 5% of the population in Germany.
Pathophysiological features of depressive disorders often include low-grade inflammation and elevated glucocorticoid output.
In a new study published in the journal Translational Psychiatry, researchers from the Technische Universität Dresden, the University of Zurich, and the Max Planck Institutes for the Science of Light and the Max-Planck-Zentrum für Physik und Medizin Erlangen establish for the first time a link between depressive disorders and mechanical changes in blood cells.
To do so, the researchers performed a cross-sectional case-control study using 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, a globally recognized clinical interview for psychiatric disorders. Using the AI method of deep learning applied to over 16 million blood cell images, the main blood cell types were classified and morpho-rheological parameters such as cell size and cell deformability of each cell were quantified.
Individuals who had suffered from persistent depressive disorder over the course of their lives showed increased cell deformability in monocytes and neutrophils, while erythrocytes were more deformable in current persistent depressive disorder. Also lymphocytes were more deformable in individuals with a current depressive disorder.
Subsequently, the study shows for the first time that depressive disorders, and in particular persistent depressive disorders that persist over a period of more than two years, are associated with increased deformability of blood cells. While all major blood cells tend to show increased deformability, lymphocytes, monocytes and neutrophils are most affected.
This suggests that mechanical changes in immune cells occur in depressive disorders, which could be causative for a sustained immune response. The identification of this pathomechanism could be accompanied by new possibilities for therapy in the future, which could restore dysfunctional cell function by improving cell mechanical processes.
For first author Dr. Andreas Walther, who conducted the study at the Chair of Biopsychology at TU Dresden but is now working at the Institute of Clinical Psychology and Psychotherapy at the University of Zurich, it means a lot to advance both biological as well as psychological therapies, that treat depressive disorders more efficiently and sustainably in the long term: “We are working in parallel on research into pharmacological therapies to improve a dysfunctional biology as well as psychological therapies to improve dysfunctional cognitive and emotional processes. Indeed, in my opinion, only a holistic approach can understand and efficiently treat this complex disorder and hopefully prevent much suffering in the future.”
Depressive disorders including major depressive disorder (MDD) and persistent depressive disorder (PDD; formerly dysthymia) are the leading causes of disability worldwide (World Health Organisation 2017). To diagnose MDD a two-week phase is required. During this phase at least one of the two cardinal symptoms “depressive mood” or “anhedonia” in combination with four or more of seven other symptoms (e.g. changes in appetite, insomnia/hypersomnia, increased fatigue, feelings of worthlessness) have to be present for most of the day and must cause functional impairment.
PDD is diagnosed based on a period of depressive mood over two-years in combination with at least two of six additional symptoms similar as for MDD 2. To date, physiological manifestations only play a theoretical role for diagnostics. This is due to the fact that the pathophysiology of depressive disorders remains insufficiently understood. The two most consistent and salient physiological abnormalities are a hyperactive hypothalamus-pituitary-adrenal (HPA) axis and chronic low-grade inflammation associated with elevated cortisol and proinflammatory cytokine levels, respectively 3.
In line with this, an increased lymphocyte count has been identified in MDD and PDD 4. Additionally, increased neutrophil and monocyte counts were described, suggesting distinct subgroups of patients based on blood cell immunophenotyping and pro-inflammatory cytokine and protein levels 5. Blood cells represent the first target of increased cortisol levels and chronic low-grade inflammation, crucially affecting lipid metabolism underlying cell membrane formation. Altered cell lipid composition is leading to increased membrane bending and destabilization 6–9. Therefore, we hypothesize depressive disorders to be associated with altered peripheral blood cell function, which might be represented by the cells morpho-rheological properties 6.
Blood is a poly-disperse suspension of a number of different cell types, representing multiple functions from metabolite transport to overall blood flow. The morpho-rheological properties including cell mechanical features or cell size of each cell can be predictive of its specific physiological or pathological function 10.
It was recently highlighted, that the assessment of the blood cell mechanical status, measured by cell deformability under constant shear stress, is appropriate to detect and classify human disease conditions 10. Furthermore, proof-of-concept studies have used optical traps 11, atomic force microscopy 12,13, or micropipette aspiration 14 to show immune cell mechanical alterations during physiological and pathological conditions. Most likely due to the overall predominance of erythrocytes, a correlation of blood cell mechanics and mental disorders has so far only been
examined by measuring erythrocyte deformability 15,16. However, immune cells seem to be more likely effectors of increased cortisol levels and increased chronic low-grade inflammation. Thus, a progress towards clinical application has yet not been achieved, potentially due to the lack of measurement throughput with only a couple of hundred cells per hour 17.
Here, we used state of the art real-time deformability cytometry (RT-DC) together with artificial intelligent-based image processing in order to overcome the throughput limitations (Figure 1). We measured the morpho-rheological properties of more than 16 x 106 single blood cells of 69 individuals at high-risk for depressive disorders and 70 matched healthy controls (HCs). RT-DC facilitates microfluidics and high-throughput imaging to assess up to 1,000 cells per second.
Based on the cell image, RT-DC quantifies multiple parameters including the cell’s deformability under shear stress and cell size without the need for blood preparation, like cell staining or erythrocyte depletion 18. The observed deformability is dependent on the cell´s mechanical properties.
These properties are representative for the molecular composition and the cytoskeletal state 19,20, which are arguably the most crucial aspects to fulfill tissue and cell-specific functionality. Thus, we argue that the precise control of mechanical features of blood cells is indispensable to keep physical and psychological homeostasis.
Thus, cell mechanical properties potentially comprise crucial pathophysiological information in mental disorders and particular in depressive disorders.
reference link :https://doi.org/10.1101/2021.07.01.21259846
More information: Andreas Walther et al, Depressive disorders are associated with increased peripheral blood cell deformability: a cross-sectional case-control study (Mood-Morph), Translational Psychiatry (2022). DOI: 10.1038/s41398-022-01911-3