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


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.


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



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.


  1. 1.
    Amminger GP, Schafer MR, Papageorgiou K, Klier CM, Cotton SM, Harrigan SM, Mackinnon A, McGorry PD, Berger GE (2010) Long-chain omega-3 fatty acids for indicated prevention of psychotic disorders: a randomized, placebo-controlled trial. Arch Gen Psychiatry 67:146–154CrossRefPubMedGoogle Scholar
  2. 2.
    APA (2000) Diagnostic and statistical manual of mental disorders, 4th revised edition (dsm-iv-tr). American Psychiatric Press, WashingtonGoogle Scholar
  3. 3.
    Atkins M, Burgess A, Bottomley C, Riccio M (1997) Chlorpromazine equivalents: a consensus of opinion for both clinical and research applications. Psychiatr Bull 21:224–226CrossRefGoogle Scholar
  4. 4.
    Badr KF, Abi-Antoun TE (2005) Isoprostanes and the kidney. Antioxid Redox Signal 7:236–243CrossRefPubMedGoogle Scholar
  5. 5.
    Basu S (1998) Metabolism of 8-iso-prostaglandin f2alpha. FEBS Lett 428:32–36CrossRefPubMedGoogle Scholar
  6. 6.
    Bayas A, Hummel V, Kallmann BA, Karch C, Toyka KV, Rieckmann P (2002) Human cerebral endothelial cells are a potential source for bioactive BDNF. Cytokine 19:55–58CrossRefPubMedGoogle Scholar
  7. 7.
    Berk M, Copolov D, Dean O, Lu K, Jeavons S, Schapkaitz I, Anderson-Hunt M, Judd F, Katz F, Katz P, Ording-Jespersen S, Little J, Conus P, Cuenod M, Do KQ, Bush AI (2008) N-acetyl cysteine as a glutathione precursor for schizophrenia–a double-blind, randomized, placebo-controlled trial. Biol Psychiatry 64:361–368CrossRefPubMedGoogle Scholar
  8. 8.
    Black CN, Bot M, Scheffer PG, Cuijpers P, Penninx BW (2015) Is depression associated with increased oxidative stress? A systematic review and meta-analysis. Psychoneuroendocrinology 51:164–175CrossRefPubMedGoogle Scholar
  9. 9.
    Black CN, Penninx BW, Bot M, Odegaard AO, Gross MD, Matthews KA, Jacobs DR Jr (2016) Oxidative stress, anti-oxidants and the cross-sectional and longitudinal association with depressive symptoms: results from the cardia study. Transl Psychiatry 6:e743CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Devanarayanan S, Nandeesha H, Kattimani S, Sarkar S (2016) Relationship between matrix metalloproteinase-9 and oxidative stress in drug-free male schizophrenia: a case control study. Clin Chem Lab Med 54(3):447–452CrossRefPubMedGoogle Scholar
  11. 11.
    Dietrich-Muszalska A, Olas B (2009) Isoprostenes as indicators of oxidative stress in schizophrenia. World J Biol Psychiatry 10:27–33CrossRefPubMedGoogle Scholar
  12. 12.
    Donovan MJ, Lin MI, Wiegn P, Ringstedt T, Kraemer R, Hahn R, Wang S, Ibanez CF, Rafii S, Hempstead BL (2000) Brain derived neurotrophic factor is an endothelial cell survival factor required for intramyocardial vessel stabilization. Development 127:4531–4540PubMedGoogle Scholar
  13. 13.
    Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctot KL (2010) A meta-analysis of cytokines in major depression. Biol Psychiatry 67:446–457CrossRefPubMedGoogle Scholar
  14. 14.
    Edelmann E, Lessmann V, Brigadski T (2014) Pre- and postsynaptic twists in BDNF secretion and action in synaptic plasticity. Neuropharmacology 76 Pt C:610–627CrossRefPubMedGoogle Scholar
  15. 15.
    Fernandes BS, Berk M, Turck CW, Steiner J, Goncalves CA (2014) Decreased peripheral brain-derived neurotrophic factor levels are a biomarker of disease activity in major psychiatric disorders: a comparative meta-analysis. Mol Psychiatry 19:750–751CrossRefPubMedGoogle Scholar
  16. 16.
    Fernandes BS, Steiner J, Berk M, Molendijk ML, Gonzalez-Pinto A, Turck CW, Nardin P, Goncalves CA (2015) Peripheral brain-derived neurotrophic factor in schizophrenia and the role of antipsychotics: meta-analysis and implications. Mol Psychiatry 20:1108–1119CrossRefPubMedGoogle Scholar
  17. 17.
    Fernandes BS, Steiner J, Bernstein HG, Dodd S, Pasco JA, Dean OM, Nardin P, Goncalves CA, Berk M (2016) C-reactive protein is increased in schizophrenia but is not altered by antipsychotics: meta-analysis and implications. Mol Psychiatry 21:554–564CrossRefPubMedGoogle Scholar
  18. 18.
    Flatow J, Buckley P, Miller BJ (2013) Meta-analysis of oxidative stress in schizophrenia. Biol Psychiatry 74:400–409CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Frijhoff J, Winyard PG, Zarkovic N, Davies SS, Stocker R, Cheng D, Knight AR, Taylor EL, Oettrich J, Ruskovska T, Gasparovic AC, Cuadrado A, Weber D, Poulsen HE, Grune T, Schmidt HH, Ghezzi P (2015) Clinical relevance of biomarkers of oxidative stress. Antioxid Redox Signal 23:1144–1170CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Fujimura H, Altar CA, Chen R, Nakamura T, Nakahashi T, Kambayashi J, Sun B, Tandon NN (2002) Brain-derived neurotrophic factor is stored in human platelets and released by agonist stimulation. Thromb Haemost 87:728–734PubMedGoogle Scholar
  21. 21.
    Fusar-Poli P, Berger G (2012) Eicosapentaenoic acid interventions in schizophrenia: meta-analysis of randomized, placebo-controlled studies. J Clin Psychopharmacol 32:179–185CrossRefPubMedGoogle Scholar
  22. 22.
    Gaebel W, Falkai P (2005) Interdisciplinary praxis guidelines: AWMF S3 guidelines of the german psychiatric association for schizophrenia. Steinkopff, DarmstadtGoogle Scholar
  23. 23.
    Giannandrea M, Parks WC (2014) Diverse functions of matrix metalloproteinases during fibrosis. Dis Model Mech 7:193–203CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Green MJ, Matheson SL, Shepherd A, Weickert CS, Carr VJ (2011) Brain-derived neurotrophic factor levels in schizophrenia: a systematic review with meta-analysis. Mol Psychiatry 16:960–972CrossRefPubMedGoogle Scholar
  25. 25.
    Halliwell B, Lee CY (2010) Using isoprostanes as biomarkers of oxidative stress: some rarely considered issues. Antioxid Redox Signal 13:145–156CrossRefPubMedGoogle Scholar
  26. 26.
    Hamazaki K, Maekawa M, Toyota T, Iwayama Y, Dean B, Hamazaki T, Yoshikawa T (2016) Fatty acid composition and fatty acid binding protein expression in the postmortem frontal cortex of patients with schizophrenia: a case-control study. Schizophr Res 171:225–232CrossRefPubMedGoogle Scholar
  27. 27.
    Hashimoto K (2015) Brain-derived neurotrophic factor (BDNF) and its precursor proBDNF as diagnostic biomarkers for major depressive disorder and bipolar disorder. Eur Arch Psychiatry Clin Neurosci 265:83–84CrossRefPubMedGoogle Scholar
  28. 28.
    Hashimoto K (2016) Regulation of brain-derived neurotrophic factor (BDNF) and its precursor proBDNF in the brain by serotonin. Eur Arch Psychiatry Clin Neurosci 266:195–197CrossRefPubMedGoogle Scholar
  29. 29.
    Hayasaka Y, Purgato M, Magni LR, Ogawa Y, Takeshima N, Cipriani A, Barbui C, Leucht S, Furukawa TA (2015) Dose equivalents of antidepressants: evidence-based recommendations from randomized controlled trials. J Affect Disord 180:179–184CrossRefPubMedGoogle Scholar
  30. 30.
    Jordan W, Cohrs S, Degner D, Meier A, Rodenbeck A, Mayer G, Pilz J, Ruther E, Kornhuber J, Bleich S (2006) Evaluation of oxidative stress measurements in obstructive sleep apnea syndrome. J Neural Transm 113:239–254CrossRefPubMedGoogle Scholar
  31. 31.
    Joshi YB, Pratico D (2014) Lipid peroxidation in psychiatric illness: overview of clinical evidence. Oxid Med Cell Longev 2014:828702CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Kerschensteiner M, Gallmeier E, Behrens L, Leal VV, Misgeld T, Klinkert WE, Kolbeck R, Hoppe E, Oropeza-Wekerle RL, Bartke I, Stadelmann C, Lassmann H, Wekerle H, Hohlfeld R (1999) Activated human t cells, b cells, and monocytes produce brain-derived neurotrophic factor in vitro and in inflammatory brain lesions: a neuroprotective role of inflammation? J Exp Med 189:865–870CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Klein AB, Williamson R, Santini MA, Clemmensen C, Ettrup A, Rios M, Knudsen GM, Aznar S (2011) Blood BDNF concentrations reflect brain-tissue BDNF levels across species. Int J Neuropsychopharmacol 14:347–353CrossRefPubMedGoogle Scholar
  34. 34.
    Kronenberg G, Mosienko V, Gertz K, Alenina N, Hellweg R, Klempin F (2016) Increased brain-derived neurotrophic factor (BDNF) protein concentrations in mice lacking brain serotonin. Eur Arch Psychiatry Clin Neurosci 266:281–284CrossRefPubMedGoogle Scholar
  35. 35.
    Lee CH, Park JH, Yoo KY, Choi JH, Hwang IK, Ryu PD, Kim DH, Kwon YG, Kim YM, Won MH (2011) Pre- and post-treatments with escitalopram protect against experimental ischemic neuronal damage via regulation of BDNF expression and oxidative stress. Exp Neurol 229:450–459CrossRefPubMedGoogle Scholar
  36. 36.
    Lopresti AL, Maker GL, Hood SD, Drummond PD (2014) A review of peripheral biomarkers in major depression: the potential of inflammatory and oxidative stress biomarkers. Prog Neuropsychopharmacol Biol Psychiatry 48:102–111CrossRefPubMedGoogle Scholar
  37. 37.
    Mahadik SP, Mukherjee S, Scheffer R, Correnti EE, Mahadik JS (1998) Elevated plasma lipid peroxides at the onset of nonaffective psychosis. Biol Psychiatry 43:674–679CrossRefPubMedGoogle Scholar
  38. 38.
    Michel TM, Pulschen D, Thome J (2012) The role of oxidative stress in depressive disorders. Curr Pharm Des 18:5890–5899CrossRefPubMedGoogle Scholar
  39. 39.
    Miller BJ, Buckley P, Seabolt W, Mellor A, Kirkpatrick B (2011) Meta-analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects. Biol Psychiatry 70:663–671CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Morrow JD, Scruggs J, Chen Y, Zackert WE, Roberts LJ 2nd (1998) Evidence that the e2-isoprostane, 15-e2t-isoprostane (8-iso-prostaglandin e2) is formed in vivo. J Lipid Res 39:1589–1593PubMedGoogle Scholar
  41. 41.
    Mukherjee A, Jenkins B, Fang C, Radke RJ, Banker G, Roysam B (2011) Automated kymograph analysis for profiling axonal transport of secretory granules. Med Image Anal 15:354–367CrossRefPubMedGoogle Scholar
  42. 42.
    Müller N (2010) Cox-2 inhibitors as antidepressants and antipsychotics: clinical evidence. Curr Opin Investig Drugs 11:31–42PubMedGoogle Scholar
  43. 43.
    Nakahashi T, Fujimura H, Altar CA, Li J, Kambayashi J, Tandon NN, Sun B (2000) Vascular endothelial cells synthesize and secrete brain-derived neurotrophic factor. FEBS Lett 470:113–117CrossRefPubMedGoogle Scholar
  44. 44.
    Nakamura K, Okada S, Ono K, Yokotani K (2003) Effects of 8-iso-prostaglandin e2 and 8-iso-prostaglandin f2 alpha on the release of noradrenaline from the isolated rat stomach. Eur J Pharmacol 470:73–78CrossRefPubMedGoogle Scholar
  45. 45.
    Opere CA, Ford K, Zhao M, Ohia SE (2008) Regulation of neurotransmitter release from ocular tissues by isoprostanes. Methods Find Exp Clin Pharmacol 30:697–701CrossRefPubMedGoogle Scholar
  46. 46.
    Palta P, Samuel LJ, Miller ER 3rd, Szanton SL (2014) Depression and oxidative stress: results from a meta-analysis of observational studies. Psychosom Med 76:12–19CrossRefPubMedGoogle Scholar
  47. 47.
    Pilz J, Meineke I, Gleiter CH (2000) Measurement of free and bound malondialdehyde in plasma by high-performance liquid chromatography as the 2,4-dinitrophenylhydrazine derivative. J Chromatogr B Biomed Sci Appl 742:315–325CrossRefPubMedGoogle Scholar
  48. 48.
    Pirici D, Pirici I, Mogoanta L, Margaritescu O, Tudorica V, Margaritescu C, Ion DA, Simionescu C, Coconu M (2012) Matrix metalloproteinase-9 expression in the nuclear compartment of neurons and glial cells in aging and stroke. Neuropathol Off J Jpn Soc Neuropathol 32:492–504CrossRefGoogle Scholar
  49. 49.
    Popa-Wagner A, Mitran S, Sivanesan S, Chang E, Buga AM (2013) Ros and brain diseases: the good, the bad, and the ugly. Oxidative Med Cell Longev 2013:963520CrossRefGoogle Scholar
  50. 50.
    Rasmussen P, Brassard P, Adser H, Pedersen MV, Leick L, Hart E, Secher NH, Pedersen BK, Pilegaard H (2009) Evidence for a release of brain-derived neurotrophic factor from the brain during exercise. Exp Physiol 94:1062–1069CrossRefPubMedGoogle Scholar
  51. 51.
    Rey MJ, Schulz P, Costa C, Dick P, Tissot R (1989) Guidelines for the dosage of neuroleptics. I: chlorpromazine equivalents of orally administered neuroleptics. Int Clin Psychopharmacol 4:95–104CrossRefPubMedGoogle Scholar
  52. 52.
    Rosenfeld RD, Zeni L, Haniu M, Talvenheimo J, Radka SF, Bennett L, Miller JA, Welcher AA (1995) Purification and identification of brain-derived neurotrophic factor from human serum. Protein Expr Purif 6:465–471CrossRefPubMedGoogle Scholar
  53. 53.
    Rybakowski JK, Remlinger-Molenda A, Czech-Kucharska A, Wojcicka M, Michalak M, Losy J (2013) Increased serum matrix metalloproteinase-9 (mmp-9) levels in young patients during bipolar depression. J Affect Disord 146:286–289CrossRefPubMedGoogle Scholar
  54. 54.
    Sawa A, Sedlak TW (2016) Oxidative stress and inflammation in schizophrenia. Schizophr Res 176:1–2CrossRefPubMedGoogle Scholar
  55. 55.
    Schwarz E, Guest PC, Steiner J, Bogerts B, Bahn S (2012) Identification of blood-based molecular signatures for prediction of response and relapse in schizophrenia patients. Transl Psychiatry 2:e82CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Schwedhelm E, Tsikas D, Durand T, Gutzki FM, Guy A, Rossi JC, Frolich JC (2000) Tandem mass spectrometric quantification of 8-iso-prostaglandin f2alpha and its metabolite 2,3-dinor-5,6-dihydro-8-iso-prostaglandin f2alpha in human urine. J Chromatogr B Biomed Sci Appl 744:99–112CrossRefPubMedGoogle Scholar
  57. 57.
    Seet RC, Lee CY, Loke WM, Huang SH, Huang H, Looi WF, Chew ES, Quek AM, Lim EC, Halliwell B (2011) Biomarkers of oxidative damage in cigarette smokers: which biomarkers might reflect acute versus chronic oxidative stress? Free Radic Biol Med 50:1787–1793CrossRefPubMedGoogle Scholar
  58. 58.
    Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, Hergueta T, Baker R, Dunbar GC (1998) The mini-international neuropsychiatric interview (m.I.N.I.): The development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 59(Suppl 20):22–33PubMedGoogle Scholar
  59. 59.
    Shigemori Y, Katayama Y, Mori T, Maeda T, Kawamata T (2006) Matrix metalloproteinase-9 is associated with blood-brain barrier opening and brain edema formation after cortical contusion in rats. Acta Neurochir Suppl 96:130–133CrossRefPubMedGoogle Scholar
  60. 60.
    Smythies J (2000) Redox aspects of signaling by catecholamines and their metabolites. Antioxid Redox Signal 2:575–583CrossRefPubMedGoogle Scholar
  61. 61.
    Steiner J, Bogerts B, Sarnyai Z, Walter M, Gos T, Bernstein HG, Myint AM (2012) Bridging the gap between the immune and glutamate hypotheses of schizophrenia and major depression: potential role of glial nmda receptor modulators and impaired blood-brain barrier integrity. World J Biol Psychiatry 13:482–492CrossRefPubMedGoogle Scholar
  62. 62.
    Tsikas D, Schwedhelm E, Suchy MT, Niemann J, Gutzki FM, Erpenbeck VJ, Hohlfeld JM, Surdacki A, Frolich JC (2003) Divergence in urinary 8-iso-pgf(2alpha) (ipf(2alpha)-iii, 15-f(2t)-IsoP) levels from gas chromatography-tandem mass spectrometry quantification after thin-layer chromatography and immunoaffinity column chromatography reveals heterogeneity of 8-iso-PGF(2alpha). Possible methodological, mechanistic and clinical implications. J Chromatogr B Analyt Technol Biomed Life Sci 794:237–255CrossRefPubMedGoogle Scholar
  63. 63.
    Vafadari B, Salamian A, Kaczmarek L (2016) Mmp-9 in translation: From molecule to brain physiology, pathology and therapy. J Neurochem 139(Suppl 2):91–114CrossRefPubMedGoogle Scholar
  64. 64.
    Valkanova V, Ebmeier KP, Allan CL (2013) Crp, il-6 and depression: a systematic review and meta-analysis of longitudinal studies. J Affect Disord 150:736–744CrossRefPubMedGoogle Scholar
  65. 65.
    van ‘t Erve TJ, Lih FB, Kadiiska MB, Deterding LJ, Eling TE, Mason RP (2015) Reinterpreting the best biomarker of oxidative stress: the 8-iso-pgf(2alpha)/pgf(2alpha) ratio distinguishes chemical from enzymatic lipid peroxidation. Free Radic Biol Med 83:245–251CrossRefGoogle Scholar
  66. 66.
    Wang H, Ward N, Boswell M, Katz DM (2006) Secretion of brain-derived neurotrophic factor from brain microvascular endothelial cells. Eur J Neurosci 23:1665–1670CrossRefPubMedGoogle Scholar
  67. 67.
    Woods SW (2003) Chlorpromazine equivalent doses for the newer atypical antipsychotics. J Clin Psychiatry 64:663–667CrossRefPubMedGoogle Scholar
  68. 68.
    Wu JH, Ward NC, Indrawan AP, Almeida CA, Hodgson JM, Proudfoot JM, Puddey IB, Croft KD (2007) Effects of alpha-tocopherol and mixed tocopherol supplementation on markers of oxidative stress and inflammation in type 2 diabetes. Clin Chem 53:511–519CrossRefPubMedGoogle Scholar
  69. 69.
    Yamamori H, Hashimoto R, Ishima T, Kishi F, Yasuda Y, Ohi K, Fujimoto M, Umeda-Yano S, Ito A, Hashimoto K, Takeda M (2013) Plasma levels of mature brain-derived neurotrophic factor (BDNF) and matrix metalloproteinase-9 (mmp-9) in treatment-resistant schizophrenia treated with clozapine. Neurosci Lett 556:37–41CrossRefPubMedGoogle Scholar
  70. 70.
    Zhang XY, Chen DC, Tan YL, Tan SP, Wang ZR, Yang FD, Okusaga OO, Zunta-Soares GB, Soares JC (2015) The interplay between BDNF and oxidative stress in chronic schizophrenia. Psychoneuroendocrinology 51:201–208CrossRefPubMedGoogle Scholar

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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