Reduced mitochondrial respiration in T cells of patients with major depressive disorder
Stefanie Gamradt,
Helge Hasselmann,
Aline Taenzer,
Jelena Brasanac,
Victoria Stiglbauer,
Arne Sattler,
Max Sajitz-Hermstein,
Sylwia Kierszniowska,
Caren Ramien,
Jan Nowacki,
Lea Mascarell-Maricic,
Katja Wingenfeld,
Dominique Piber,
Andreas Ströhle,
Katja Kotsch,
Friedemann Paul,
Christian Otte,
Stefan M. Gold
Affiliations
Stefanie Gamradt
Charité – Universitätsmedizin Berlin, Klinik für Psychiatrie und Psychotherapie, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany
Helge Hasselmann
Charité – Universitätsmedizin Berlin, Klinik für Psychiatrie und Psychotherapie, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany
Aline Taenzer
Charité – Universitätsmedizin Berlin, Klinik für Psychiatrie und Psychotherapie, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany
Jelena Brasanac
Charité – Universitätsmedizin Berlin, Klinik für Psychiatrie und Psychotherapie, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany; Charité – Universitätsmedizin Berlin and Max Delbrueck Center for Molecular Medicine, NeuroCure Clinical Research Center (NCRC), Campus Mitte, 10117 Berlin, Germany
Victoria Stiglbauer
Charité – Universitätsmedizin Berlin, Klinik für Psychiatrie und Psychotherapie, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany
Arne Sattler
Charité – Universitätsmedizin Berlin, Klinik für Allgemein- und Viszeralchirurgie, Campus Benjamin Franklin, 12203 Berlin, Germany
Max Sajitz-Hermstein
metaSysX GmbH, 14476 Potsdam, Germany
Sylwia Kierszniowska
metaSysX GmbH, 14476 Potsdam, Germany
Caren Ramien
Institut für Neuroimmunologie und Multiple Sklerose (INIMS), Zentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg Eppendorf, 20251 Hamburg, Germany
Jan Nowacki
Charité – Universitätsmedizin Berlin, Klinik für Psychiatrie und Psychotherapie, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany
Lea Mascarell-Maricic
Charité – Universitätsmedizin Berlin, Klinik für Psychiatrie und Psychotherapie, Campus Mitte, 10117 Berlin, Germany
Katja Wingenfeld
Charité – Universitätsmedizin Berlin, Klinik für Psychiatrie und Psychotherapie, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany
Dominique Piber
Charité – Universitätsmedizin Berlin, Klinik für Psychiatrie und Psychotherapie, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany
Andreas Ströhle
Charité – Universitätsmedizin Berlin, Klinik für Psychiatrie und Psychotherapie, Campus Mitte, 10117 Berlin, Germany
Katja Kotsch
Charité – Universitätsmedizin Berlin, Klinik für Allgemein- und Viszeralchirurgie, Campus Benjamin Franklin, 12203 Berlin, Germany
Friedemann Paul
Charité – Universitätsmedizin Berlin and Max Delbrueck Center for Molecular Medicine, NeuroCure Clinical Research Center (NCRC), Campus Mitte, 10117 Berlin, Germany
Christian Otte
Charité – Universitätsmedizin Berlin, Klinik für Psychiatrie und Psychotherapie, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany
Stefan M. Gold
Charité – Universitätsmedizin Berlin, Klinik für Psychiatrie und Psychotherapie, Campus Benjamin Franklin, Hindenburgdamm 30, 12203 Berlin, Germany; Institut für Neuroimmunologie und Multiple Sklerose (INIMS), Zentrum für Molekulare Neurobiologie, Universitätsklinikum Hamburg Eppendorf, 20251 Hamburg, Germany; Charité – Universitätsmedizin Berlin, Medizinische Klinik m.S. Psychosomatik, Campus Benjamin Franklin, 12203 Berlin, Germany; Corresponding author
Summary: Converging evidence indicates that major depressive disorder (MDD) and metabolic disorders might be mediated by shared (patho)biological pathways. However, the converging cellular and molecular signatures remain unknown. Here, we investigated metabolic dysfunction on a systemic, cellular, and molecular level in unmedicated patients with MDD compared with matched healthy controls (HC). Despite comparable BMI scores and absence of cardiometabolic disease, patients with MDD presented with significant dyslipidemia. On a cellular level, T cells obtained from patients with MDD exhibited reduced respiratory and glycolytic capacity. Gene expression analysis revealed increased carnitine palmitoyltransferase IA (CPT1a) levels in T cells, the rate-limiting enzyme for mitochondrial long-chain fatty acid oxidation. Together, our results indicate metabolic dysfunction in unmedicated, non-overweight patients with MDD on a systemic, cellular, and molecular level. This evidence for reduced mitochondrial respiration in T cells of patients with MDD provides translation of previous animal studies regarding a putative role of altered immunometabolism in depression pathobiology.
