Mitochondrial respiration in peripheral blood mononuclear cells correlates with depressive subsymptoms and severity of major depression

Abstract

Mitochondrial dysfunction might have a central role in the pathophysiology of depression. Phenotypically, depression is characterized by lack of energy, concentration problems and fatigue. These symptoms might be partially explained by reduced availability of adenosine triphosphate (ATP) as a consequence of impaired mitochondrial functioning. This study investigated mitochondrial respiration in peripheral blood mononuclear cells (PBMCs), an established model to investigate the pathophysiology of depression. Mitochondrial respiration was assessed in intact PBMCs in 22 individuals with a diagnosis of major depression (MD) compared with 22 healthy age-matched controls using high-resolution respirometry. Individuals with MD showed significantly impaired mitochondrial functioning: routine and uncoupled respiration as well as spare respiratory capacity, coupling efficiency and ATP turnover-related respiration were significantly lower in the MD compared with the control group. Furthermore, mitochondrial respiration was significantly negatively correlated with the severity of depressive symptoms, in particular, with loss of energy, difficulties concentrating and fatigue. The results suggest that mitochondrial dysfunction contributes to the biomolecular pathophysiology of depressive symptoms. The decreased immune capability observed in MD leading to a higher risk of comorbidities could be attributable to impaired energy supply due to mitochondrial dysfunction. Thus mitochondrial respiration in PBMCs and its functional consequences might be an interesting target for new therapeutical approaches in the treatment of MD and immune-related comorbidities.

Figure 1

Boxplots of group-wise comparison of respiration in PBMCs from MD patients (n = 19) and control subjects (n  = 19) characterized by mitochondrial oxygen flux (J_O2) per cell. Circles and triangles represent statistical outliers of the respective groups. Asterisk (*) indicates significant group differences on an alpha level of 0.05 (one-tailed Mann–Whitney U test or Student's independent t-test). MD, major depression; PBMCs, peripheral blood mononuclear cells; SRC, spare respiratory capacity.

Figure 2

Boxplots of group-wise comparison of respiration in PBMCs from MD patients (n = 19) and control subjects (n = 19) characterized by flux control ratios. Circles and triangles represent statistical outliers of the respective groups. Asterisk (*) indicates significant group differences on an alpha level of 0.05 (one-tailed Mann–Whitney U test or Student's independent t-test, respectively). MD, major depression; PBMCs, peripheral blood mononuclear cells.

Figure 3

Graphical illustration of the correlation analysis between mitochondrial respiration in PBMCs and depressive symptom severity (BDI, MADRS; sum score and selected subscales) as well as ‘traumatic load' (ETI). The horizontal scale shows Kendall's τ rank correlation coefficient, dashed vertical lines indicate absence of association (τ = 0). Respective τ coefficients are given as circles with 95% confidence intervals as horizontal bars. Black circles mark a correlation with a significance of P<0.01, grey circles mark a significance of 0.01⩾P<0.05 and white circles mark nonsignificant correlations (one-tailed Kendall-τ-b correlation analysis). ATP, adenosine triphosphate; BDI, Beck Depression Inventory II; ETI, Essener Trauma Inventory; MADRS, Montgomery-Asberg Depression Rating Scale; PBMCs, peripheral blood mononuclear cells.