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

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.

Central and paracentral corneal pachymetry in patients with normal tension glaucoma and ocular hypertension.

PURPOSE: The difference in central corneal thickness among subgroups of glaucoma patients, as well as its influence on Goldmann applanation tonometry, has been well documented in several clinical trials. In the present study, possible similarities and differences between central corneal thickness and corneal thickness of paracentral quadrants in patients with normal tension glaucoma (NTG) and ocular hypertension (OHT) were investigated. METHODS: Central and paracentral corneal thickness was measured by optical slit scan pachymetry (Orbscan II). Fourteen patients (28 eyes) with NTG and 11 patients (22 eyes) with OHT were included in this study. t-Test was performed for statistical analysis. To evaluate overall corneal topography, the mean and SD values of the differences between the central corneal thickness and each peripheral quadrant were analysed. RESULTS: The following data was obtained (microm): (central, upper, temporal, nasal, inferior paracentral quadrant): OHT group 617-695-663-687-660. NTG group 568-629-593-612-616. Corneal thickness of all four paracentral quadrants differed significantly between the OHT and NTG groups. There was a more heterogeneous intraindividual pattern of overall corneal topography in the OHT group, and a more heterogeneous pattern of corneal topography among the individuals of the NTG group (interindividual heterogeneity). CONCLUSIONS: A comparison of central corneal thickness and paracentral corneal thickness revealed clinically relevant differences between the OHT and NTG groups. The presented data underlines the importance of correlating the site of applanation with the corresponding corneal thickness, especially in OHT patients. It further substantiates the necessity to obtain individual pachymetric data for each NTG patient.