Figure 2.

Decreased mitochondrial respiration in T cells of patients with MDD

(A and B) To quantify mitochondrial respiration (A) as well as glycolytic activity (B) of CD3⁺ T cells from 28 patients with MDD and 28 matched HC different modulators of respiration were added sequentially to the cells (see also Figure S1) and the oxygen consumption rate (OCR) as well as the extracellular acidification rate (ECAR) were determined over time in a Seahorse XFe96 Analyzer (mean ± SEM is shown, all assays run in three to five replicates for each subject).

(C and D) The main parameters of mitochondrial respiration (basal respiration, ATP production, and spare respiratory capacity) (C) as well as the coupling efficiency expressed as the % of basal respiration coupled to ATP production (CE%) (D) are shown. See also Figure S1 for further information regarding the calculation of these parameters from OCR measurements. Individual patient data and median are shown. Wilcoxon signed-rank test was used to compare groups.

(E) OCR and ECAR values under baseline and stressed conditions (after addition of Oligomycin and FCCP) were plotted against each other to visualize the energy phenotype of the cells (mean ± SEM shown).

(F) Spearman rank correlations of systemic and T cell markers with individual MADRS items. Circle sizes indicate magnitude of correlation, color shading depicts magnitude and direction of correlation (Spearman's rho, see legend). Asterisks were added to the circles if p < 0.005.

Oligomycin, ATP synthase inhibitor; carbonyl cyanide-4(trifluoromethoxy) phenylhydrazone (FCCP), uncoupling agent; Rotenone/Antimycin A, complex I/III inhibitors; BR, basal respiration; CRP, C-reactive protein; IL-6, interleukin 6; LDL/HDL, low/high density lipoprotein; MADRS, Montgomery-Asberg Depression Rating Scale; SRC, Spare Respiratory Capacity; TNF, tumor necrosis factor; WHR, waist/hip ratio. Individual patient data for the Seahorse readouts presented here are provided in the supplementary data file, Data S1.