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Oxidative stress in drug-naïve first episode patients with schizophrenia and major depression: effects of disease acuity and potential confounders

  • Wolfgang Jordan
  • Henrik Dobrowolny
  • Sabine Bahn
  • Hans-Gert Bernstein
  • Tanja Brigadski
  • Thomas Frodl
  • Berend Isermann
  • Volkmar Lessmann
  • Jürgen Pilz
  • Andrea Rodenbeck
  • Kolja Schiltz
  • Edzard Schwedhelm
  • Hayrettin Tumani
  • Jens Wiltfang
  • Paul C. Guest
  • Johann Steiner
Original Paper

Abstract

Oxidative stress and immune dysregulation have been linked to schizophrenia and depression. However, it is unknown whether these factors are related to the pathophysiology or whether they are an epiphenomenon. Inconsistent oxidative stress-related findings in previous studies may have resulted from the use of different biomarkers which show disparate aspects of oxidative stress. Additionally, disease severity, medication, smoking, endocrine stress axis activation and obesity are potential confounders. In order to address some of these shortcomings, we have analyzed a broader set of oxidative stress biomarkers in our exploratory study, including urinary 8-iso-prostaglandin F2α (8-iso-PGF2α), 8-OH-2-deoyxguanosine (8-OH-2-dG), and blood levels of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione S-transferase (GST) in acutely ill drug-naïve first episode patients with schizophrenia (n = 22), major depression (n = 18), and controls (n = 43). Possible confounding factors were considered, and patients were followed-up after 6 weeks of treatment. No differences were observed regarding 8-OH-2-dG, MDA and GST. At baseline, 8-iso-PGF2α levels were higher in patients with schizophrenia (p = 0.004) and major depression (p = 0.037), with a trend toward higher SOD concentrations in schizophrenia (p = 0.053). After treatment, schizophrenia patients showed a further increase in 8-iso-PGF2α (p = 0.016). These results were not related to age, sex, disease severity, medication or adipose tissue mass. However, 8-iso-PGF2α was associated with smoking, endocrine stress axis activation, C-reactive protein levels and low plasma concentrations of brain-derived neurotrophic factor. This study suggests a role of lipid peroxidation particularly in drug-naïve acutely ill schizophrenia patients and highlights the importance of taking into account other confounding factors in biomarker studies.

Keywords

Oxidative stress Schizophrenia Depression 8-Iso-prostaglandin F2α Isoprostane Malondialdehyde 8-OH-2-deoyxguanosine Superoxide dismutase Glutathione S-transferase 

Notes

Acknowledgements

Anke Dudeck, Gabriela Meyer-Lotz and Jeanette Schadow participated in the sample characterization and collection. Katrin Borucki provided helpful advice during manuscript preparation. This study has been performed without extra funding.

Compliance with ethical standards

Conflicts of interest

SB is a director of Psynova Neurotech Ltd and PsyOmics Ltd. All other authors declare no conflicts of interest.

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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Wolfgang Jordan
    • 1
    • 2
  • Henrik Dobrowolny
    • 3
  • Sabine Bahn
    • 4
  • Hans-Gert Bernstein
    • 3
  • Tanja Brigadski
    • 5
    • 6
  • Thomas Frodl
    • 3
    • 6
  • Berend Isermann
    • 7
  • Volkmar Lessmann
    • 5
    • 6
  • Jürgen Pilz
    • 8
  • Andrea Rodenbeck
    • 9
    • 10
  • Kolja Schiltz
    • 3
    • 6
  • Edzard Schwedhelm
    • 11
  • Hayrettin Tumani
    • 12
    • 13
  • Jens Wiltfang
    • 2
    • 14
  • Paul C. Guest
    • 15
  • Johann Steiner
    • 3
    • 6
  1. 1.Department of Psychiatry and PsychotherapyMagdeburg Hospital GmbHMagdeburgGermany
  2. 2.Department of Psychiatry and PsychotherapyUniversity of GoettingenGoettingenGermany
  3. 3.Department of Psychiatry and PsychotherapyUniversity of MagdeburgMagdeburgGermany
  4. 4.Department of Chemical Engineering and BiotechnologyUniversity of CambridgeCambridgeUK
  5. 5.Institute of PhysiologyUniversity of MagdeburgMagdeburgGermany
  6. 6.Center for Behavioral Brain SciencesMagdeburgGermany
  7. 7.Institute of Clinical Chemistry and PathobiochemistryUniversity of MagdeburgMagdeburgGermany
  8. 8.Laboratory of Stress MonitoringHardegsenGermany
  9. 9.Sleep Laboratory, Department of PneumologyEvangelisches Krankenhaus Goettingen-Weende gGmbHGoettingenGermany
  10. 10.Department of Sleep Medicine and Clinical Chronobiology, Institute of Physiology, St. Hedwig Hospital, ChariteUniversity of BerlinBerlinGermany
  11. 11.Institute of Experimental and Clinical Pharmacology and ToxicologyUniversity Medical Center Hamburg-EppendorfHamburgGermany
  12. 12.Department of NeurologyUniversity of UlmUlmGermany
  13. 13.Fachklinik für Neurologie DietenbronnSchwendiGermany
  14. 14.German Center for Neurodegenerative Diseases (DZNE)GoettingenGermany
  15. 15.Department of Biochemistry and Tissue BiologyUniversity of Campinas (UNICAMP)CampinasBrazil

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