Karabatsiakis 2015 Abstract MiP2015

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Mitochondrial respiration of peripheral blood mononuclear cells in patients with borderline personality disorder.

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Karabatsiakis A, Rappel M, Calzia E, Jungkunz M, Schmahl C, Bohus M, Kolassa IT (2015)

Event: MiP2015

Borderline personality disorder (BPD) is characterised by a pervasive pattern of instability of interpersonal relationships, self-image, affects, and marked by impulsivity [1]. Beside the pronounced psychological stress, patients with BPD show an increased risk for somatic disorders and an impaired immunity. The resulting high burden of patients suffering from BPD is associated with conditions of chronic stress, which negatively influences the reactivity of the cellular immune system [2,3]. So far, the underlying pathophysiological processes and long-term consequences of BPD on cellular immunity and energy metabolism are hardly explored.

Here, we report first data on mitochondrial functioning and the quantity of mitochondria in immune cells from female patients with BPD (n = 24), which were compared to an age- and gender-matched group of healthy controls (n = 13). The severity of BPD symptoms was measured by the self-report questionnaire Borderline Symptom List (BSL), the severity of depressive symptoms by the Beck Depression Inventory (BDI). Peripheral blood mononuclear cells (PBMC) were isolated from whole blood (15 ml) using Ficoll dense gradient centrifugation. Total PBMC were cryopreserved in Mannheim and after thawing in Ulm, the respiratory activity was assessed in living cells in a high-resolution oxygraph 2k. Characterization of mitochondrial activity included the following parameters: ROUTINE, LEAK, uncoupled (ET-pathway), and Residual oxygen consumption (ROX). Respiration was controlled for the intracellular amount of mitochondria, which was assessed with the citrate synthase activity (CSA) assay, a spectrophotometric technique [4].

We found no statistically significant alterations of mitochondrial activity in patients with BPD compared to controls. Interestingly, within the BPD group ATP turnover-related oxygen consumption was significantly correlated with both the severity of BPD (BSL sum score, r = 0.592, p = 0.010) and depressive symptoms (BDI sum score, r = 0.735, p = 0.001). Furthermore, there was a significant effect of depressive symptoms (BDI sum score) on residual oxygen consumption (ROX), the amount of oxygen consumed independently from ATP-production (r = 0.450, p = 0.053). Finally, the CSA assay revealed no significant difference in the amount of mitochondria between the two groups. Chronic stress associated with BPD seems to negatively affect the homeostasis of immune cells, which has to be counteracted by a higher production of ATP. The increase of ROX subject to the severity of depressive symptoms provides evidence for the production of reactive oxygen species (ROS) in a dose-dependent manner. Consequently, the severity of depressive symptoms seems to have a stronger impact on mitochondrial functioning in immune cells than the severity of BPD. To address the question of a possible usage of mitochondrial respiration in immune cells as a new marker for the biological effects of BPD treatment, follow-up intervention studies with a longitudinal design are necessary.

Keywords: PBMC

O2k-Network Lab: DE Ulm Karabatsiakis A, DE Ulm Radermacher P


Labels: MiParea: Respiration, Patients  Pathology: Other  Stress:Cryopreservation  Organism: Human  Tissue;cell: Blood cells 


Coupling state: LEAK, ROUTINE, OXPHOS, ET  Pathway: ROX  HRR: Oxygraph-2k  Event: C1, Oral  MiP2015 

Affiliations

1-Clinical Biol Psychol, Inst Psychol Education, Ulm Univ, Germany; 2-Dept Anesthesia, Section Anesthesiol Pathophysiol Process Developm, Univ Hospital Ulm, Germany; 3-Dept Psychosomatic Med Psychotherapy, Central Inst Mental Health, Medical Faculty Mannheim, University of Heidelberg, Germany. - Alexander.Karabatsiakis@uni-ulm.de

References and acknowledgements

  1. American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders (5th ed.) Washington, DC: Author.
  2. El-Gabalawy R, Katz LY, Sareen J (2010) Comorbidity and associated severity of borderline personality disorder and physical health conditions in a nationally representative sample. Psychosom Med 72:641-7.
  3. Kahl KG, Bens S, Ziegler K, Rudolf S, Dibbelt L, Kordon A, Schweiger U (2006) Cortisol, the cortisol-dehydroepiandrosterone ratio, and pro-inflammatory cytokines in patients with current major depressive disorder comorbid with borderline personality disorder. Biol Psychiatry 59:667-71.
  4. Eigentler A, Draxl A, Wiethüchter A, Kuznetsov A, Lassing B, Gnaiger E (2012) Laboratory protocol: citrate synthase. A mitochondrial marker enzyme. Mitoch Physiol Network 17.04:1-11.