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.

Transcriptional profiling of mitochondria associated genes in prefrontal cortex of subjects with major depressive disorder

“…On the other hand, respiratory rates were unchanged in permeabilized platelets of MDD patients. Karabatsiakis et al (2014) also confirmed that mitochondrial respiration of PBMCs is significantly decreased in MDD patients. Importantly, decline of respiratory activity is negatively correlated with the severity of depressive symptoms, such as loss of energy, difficulties concentrating and fatigue etc.…”

“…They also showed a significant decrease of mitochondrial ATP production rates and mitochondrial enzyme ratios in the MDD muscles compared to controls. Two other groups investigated mitochondrial respiration via high-resolution respirometry in the intact and permeabilized platelets of MDD patients and found significant decrease of respiration efficiency in intact platelets in this population (Hroudová et al 2013; Karabatsiakis et al 2014). On the other hand, respiratory rates were unchanged in permeabilized platelets of MDD patients.…”

“…Importantly, decline of respiratory activity is negatively correlated with the severity of depressive symptoms, such as loss of energy, difficulties concentrating and fatigue etc. (Karabatsiakis et al 2014). …”

The Depressed Frail Phenotype: The Clinical Manifestation of Increased Biological Aging

“…Over the last fifteen years, research has identified physiological changes associated with depressive disorders that are consistent with increased biological aging (defined as systemic aging beyond that which is expected for one’s chronological age). 29–32 The proliferation of mitochondrial DNA damage or dysfunction, mitochondrial dysfunction associated with oxidative stress both in the brain and the periphery, and increased proinflammatory cytokines such as tumor necrosis factor alpha (TNFα) or Interleukin 6 (IL6) are associated with a cycle resulting in cellular senescence and apoptosis, 33 major depression and other psychiatric illnesses, 34,35 and decreased physical activities, slowing and mobility deficits, and decrements in energy capacity in older adults. 36–39 Furthermore, depression in late life is associated with greater decrements in physical functioning.…”

Transcranial Low-Level Laser Therapy for Depression and Alzheimer’s Disease

“…These clinical symptoms may be partly attributed to reduced synthesis of adenosine triphosphate (ATP) due to mitochondrial dysfunction [41][42][43]. ATP, which is produced by mitochondria, is the main source of cellular energy.…”