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

A Karabatsiakis,S Kolassa,I-T Kolassa,D E Dietrich,J Salinas-Manrique,C Böck,E Calzia

doi:10.1038/tp.2014.44

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.

Highlights

The potential role of mitochondria in depressionMitochondria produce adenosine triphosphate (ATP)—the main source of cellular energy
Mitochondrial respiration of peripheral blood mononuclear cells (PBMCs) is significantly decreased in major depression (MD) patients PBMCs of the MD group showed a significantly lower routine respiration and maximal uncoupled respiration compared with the control group (Table 2, Figure 1)
This study shows that the rate of mitochondrial respiration in PBMCs of acutely depressed individuals is reduced compared with healthy controls

Summary

Introduction

Mitochondria produce adenosine triphosphate (ATP)—the main source of cellular energy. Energy that is liberated during the degradation of dietary intermediates is conserved via the mitochondrial respiratory chain as the so-called proton motive force across the inner mitochondrial membrane. The enzyme ATP synthase utilizes the energy conserved as the proton motive force for the conversion of adenosine diphosphate and inorganic phosphate to ATP. Mitochondrial dysfunction has been suggested to have an important role in the pathophysiology of major depression (MD).[5] Characteristic depressive symptoms, for example, physiological (sleeping disturbances), psychological (lack of motivation) and neurocognitive alterations (lack of concentration, working memory deficits),[6] might be explained on the one hand by pro-inflammatory states and sickness behaviour, which are commonly observed in depression,[7] and on the other hand by alterations in energy metabolism and availability of ATP

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Discussion

Conclusion