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

Simon, Maria S ; Schiweck, Carmen ; Arteaga-Henriquez, Gara ; Poletti, Sara ; Haarman, Bartholomeus CM ; 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 ; Drexhage, Hemmo A

PERGAMON-ELSEVIER SCIENCE LTD 2021-06

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Título:
Monocyte mitochondrial dysfunction, inflammaging, and inflammatory pyroptosis in major depression
Autor: Simon, Maria S ; Schiweck, Carmen ; Arteaga-Henriquez, Gara ; Poletti, Sara ; Haarman, Bartholomeus CM ; 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 ; Drexhage, Hemmo A
Assuntos: Apoptosis ; Childhood adversity ; CHOLESTEROL ; Cholesterol pathway ; Clinical Neurology ; DIAGNOSIS ; DISORDER ; GENE-EXPRESSION ; HISTORY ; Inflammation ; Life Sciences & Biomedicine ; Major depressive disorder ; METAANALYSIS ; Neurosciences ; Neurosciences & Neurology ; PATHWAY ; PCR ; Pharmacology & Pharmacy ; Psychiatry ; Science & Technology ; STRESS
Notas: location:England
PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY vol:111
Descrição: 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. status: published
Editor: PERGAMON-ELSEVIER SCIENCE LTD
Data de criação/publicação: 2021-06
Idioma: Inglês

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

PERGAMON-ELSEVIER SCIENCE LTD 2021-06

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