Monocyte mitochondrial dysfunction, inflammaging, and inflammatory pyroptosis in major depression

Simon, Maria S.; Schiweck, Carmen; Arteaga-Henriquez, Gara; Poletti, Sara; Haarman, Bartholomeus C. M.; Dik, Wim A.; Schwarz, Markus; Vrieze, Elske; Mikova, Olya; Joergens, Silke; Musil, Richard; Claes, Stephan; Baune, Bernhard T.; Leboyer, Marion; Benedetti, Francesco; Furlan, Roberto; Berghmans, Raf; de Wit, Harm; Wijkhuijs, Annemarie; Arolt, Volker; Mueller, Norbert and Drexhage, Hemmo A. (2021): Monocyte mitochondrial dysfunction, inflammaging, and inflammatory pyroptosis in major depression. In: Progress in Neuro-Psychopharmacology & Biological Psychiatry, Vol. 111, 110391

Abstract

Background: The macrophage theory of depression states that macrophages play an important role in Major Depressive Disorder (MDD). Methods: MDD patients (N = 140) and healthy controls (N = 120) participated in a cross-sectional study investigating the expression of apoptosis/growth and lipid/cholesterol pathway genes (BAX, BCL10, EGR1, EGR2, HB-EGF, NR1H3, ABCA1, ABCG1, MVK, CD163, HMOX1) in monocytes (macrophage/microglia precursors). Gene expressions were correlated to a set of previously determined and reported inflammation-regulating genes and analyzed with respect to various clinical parameters. Results: MDD monocytes showed an overexpression of the apoptosis/growth/cholesterol and the TNF genes forming an inter-correlating gene cluster (cluster 3) separate from the previously described inflammation-related gene clusters (containing IL1 and IL6). While upregulation of monocyte gene cluster 3 was a hallmark of monocytes of all MDD patients, upregulation of the inflammation-related clusters was confirmed to be found only in the monocytes of patients with childhood adversity. The latter group also showed a downregulation of the cholesterol metabolism gene MVK, which is known to play an important role in trained immunity and proneness to inflammation. Conclusions: The upregulation of cluster 3 genes in monocytes of all MDD patients suggests a premature aging of the cells, i.e. mitochondrial apoptotic dysfunction and TNF inflammaging, as a general feature of MDD. The overexpression of the IL-1/IL-6 containing inflammation clusters and the downregulation of MVK in monocytes of patients with childhood adversity indicates a shift in this condition to a more severe inflammation form (pyroptosis) of the cells, additional to the signs of premature aging and inflammaging.

• Item Type: Journal article
• Faculties: Medicine
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 0278-5846
• Language: English