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Acute schizophrenia is accompanied by reduced T cell and increased B cell immunity

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Abstract

Previous studies of lymphocyte distribution in schizophrenia have yielded inconsistent results, as summarized in the present study. Based on our own original data, potential confounds that might explain these variations are analyzed and discussed. Blood samples from 26 patients with acute paranoid schizophrenia were investigated in comparison with 32 matched healthy controls by flow cytometry (CD3, CD4, CD8, CD19, and CD56 phenotyping). A subgroup of drug-free patients was followed up after 6 weeks of treatment. Cotinine levels and the free cortisol index (FCI) were provided in order to control for medication, smoking, and stress. Cotinine levels correlated with natural killer (NK) cell counts (CD3−/CD56+: r = −0.383, P = 0.003) while the FCI was related to B cell numbers (CD19+: r = 0.390, P = 0.003). Considering these covariates, a lower level of T helper cells (P = 0.010), a reduced CD4/CD8 ratio (P = 0.029), and elevated B cells (P = 0.008) were found during acute psychosis. After 6 weeks of medication, an inverse pattern was observed in initially drug-free patients: total T cell (P = 0.005), T helper (P = 0.003), and T suppressor/cytotoxic cells (P = 0.005) increased, while B cell counts declined (P = 0.049). In conclusion, acute paranoid schizophrenia may be accompanied by a reduced T cell defense and a shift towards B cell immunity, which normalizes in response to treatment. In addition to disease stage or subtype and medication, cigarette smoking and stress are important co-factors.

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References

  1. APA (2000) Diagnostic and statistical manual of mental disorders, 4th revised edition (DSM-IV-TR). American Psychiatric Press, Washington

    Google Scholar 

  2. Baskak SC, Ozsan H, Baskak B, Devrimci Ozguven H, Kinikli G (2008) Peripheral blood T-lymphocyte and T-lymphocyte subset ratios before and after treatment in schizophrenia patients not taking antipsychotic medication. Turk Psikiyatri Derg 19:5–12

    PubMed  Google Scholar 

  3. Bilici M, Tekelioglu Y, Efendioglu S, Ovali E, Ulgen M (2003) The influence of olanzapine on immune cells in patients with schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 27:483–485

    Article  CAS  PubMed  Google Scholar 

  4. Borda T, Perez Rivera R, Joensen L, Gomez RM, Sterin-Borda L (2002) Antibodies against cerebral M1 cholinergic muscarinic receptor from schizophrenic patients: molecular interaction. J Immunol 168:3667–3674

    CAS  PubMed  Google Scholar 

  5. Bramer SL, Kallungal BA (2003) Clinical considerations in study designs that use cotinine as a biomarker. Biomarkers 8:187–203

    Article  CAS  PubMed  Google Scholar 

  6. Brisch R, Bernstein HG, Krell D, Stauch R, Trubner K, Dobrowolny H, Kropf S, Bielau H, Bogerts B (2007) Volumetric analysis of septal region in schizophrenia and affective disorder. Eur Arch Psychiatry Clin Neurosci 257:140–148

    Article  PubMed  Google Scholar 

  7. Brown AS, Begg MD, Gravenstein S, Schaefer CA, Wyatt RJ, Bresnahan M, Babulas VP, Susser ES (2004) Serologic evidence of prenatal influenza in the etiology of schizophrenia. Arch Gen Psychiatry 61:774–780

    Article  PubMed  Google Scholar 

  8. Cohen J (1992) A power primer. Psychol Bull 112:155–159

    Article  CAS  PubMed  Google Scholar 

  9. Coste J, Strauch G, Letrait M, Bertagna X (1994) Reliability of hormonal levels for assessing the hypothalamic–pituitary–adrenocortical system in clinical pharmacology. Br J Clin Pharmacol 38:474–479

    CAS  PubMed  Google Scholar 

  10. Craddock RM, Lockstone HE, Rider DA, Wayland MT, Harris LJ, McKenna PJ, Bahn S (2007) Altered T-cell function in schizophrenia: a cellular model to investigate molecular disease mechanisms. PLoS ONE 2:e692

    Article  PubMed  Google Scholar 

  11. Drzyzga L, Obuchowicz E, Marcinowska A, Herman ZS (2006) Cytokines in schizophrenia and the effects of antipsychotic drugs. Brain Behav Immun 20:532–545

    Article  CAS  PubMed  Google Scholar 

  12. Eaton WW, Byrne M, Ewald H, Mors O, Chen CY, Agerbo E, Mortensen PB (2006) Association of schizophrenia and autoimmune diseases: linkage of Danish national registers. Am J Psychiatry 163:521–528

    Article  PubMed  Google Scholar 

  13. Frazer-Abel AA, Baksh S, Fosmire SP, Willis D, Pierce AM, Meylemans H, Linthicum DS, Burakoff SJ, Coons T, Bellgrau D, Modiano JF (2004) Nicotine activates nuclear factor of activated T cells c2 (NFATc2) and prevents cell cycle entry in T cells. J Pharmacol Exp Ther 311:758–769

    Article  CAS  PubMed  Google Scholar 

  14. Ganguli R, Rabin BS (1993) CD5 positive B lymphocytes in schizophrenia: no alteration in numbers or percentage as compared with control subjects. Psychiatry Res 48:69–78

    Article  CAS  PubMed  Google Scholar 

  15. Geng Y, Savage SM, Johnson LJ, Seagrave J, Sopori ML (1995) Effects of nicotine on the immune response. I. Chronic exposure to nicotine impairs antigen receptor-mediated signal transduction in lymphocytes. Toxicol Appl Pharmacol 135:268–278

    Article  CAS  PubMed  Google Scholar 

  16. Geng Y, Savage SM, Razani-Boroujerdi S, Sopori ML (1996) Effects of nicotine on the immune response. II. Chronic nicotine treatment induces T cell anergy. J Immunol 156:2384–2390

    CAS  PubMed  Google Scholar 

  17. Gladkevich A, Kauffman HF, Korf J (2004) Lymphocytes as a neural probe: potential for studying psychiatric disorders. Prog Neuropsychopharmacol Biol Psychiatry 28:559–576

    Article  PubMed  Google Scholar 

  18. Henneberg A, Riedl B, Dumke HO, Kornhuber HH (1990) T-lymphocyte subpopulations in schizophrenic patients. Eur Arch Psychiatry Neurol Sci 239:283–284

    Article  CAS  PubMed  Google Scholar 

  19. Herbert TB, Cohen S (1993) Stress and immunity in humans: a meta-analytic review. Psychosom Med 55:364–379

    CAS  PubMed  Google Scholar 

  20. Holt PG, Keast D (1977) Environmentally induced changes in immunological function: acute and chronic effects of inhalation of tobacco smoke and other atmospheric contaminants in man and experimental animals. Bacteriol Rev 41:205–216

    CAS  PubMed  Google Scholar 

  21. Ilani T, Strous RD, Fuchs S (2004) Dopaminergic regulation of immune cells via D3 dopamine receptor: a pathway mediated by activated T cells. FASEB J 18:1600–1602

    CAS  PubMed  Google Scholar 

  22. Ising M, Kunzel HE, Binder EB, Nickel T, Modell S, Holsboer F (2005) The combined dexamethasone/CRH test as a potential surrogate marker in depression. Prog Neuropsychopharmacol Biol Psychiatry 29:1085–1093

    Article  CAS  PubMed  Google Scholar 

  23. Johnson JD, Houchens DP, Kluwe WM, Craig DK, Fisher GL (1990) Effects of mainstream and environmental tobacco smoke on the immune system in animals and humans: a review. Crit Rev Toxicol 20:369–395

    Article  CAS  PubMed  Google Scholar 

  24. Kalman D, Morissette SB, George TP (2005) Co-morbidity of smoking in patients with psychiatric and substance use disorders. Am J Addict 14:106–123

    Article  PubMed  Google Scholar 

  25. Kalra R, Singh SP, Kracko D, Matta SG, Sharp BM, Sopori ML (2002) Chronic self-administration of nicotine in rats impairs T cell responsiveness. J Pharmacol Exp Ther 302:935–939

    Article  CAS  PubMed  Google Scholar 

  26. Kay SR, Fiszbein A, Opler LA (1987) The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 13:261–276

    CAS  PubMed  Google Scholar 

  27. Keilhoff G, Grecksch G, Bernstein HG, Roskoden T, Becker A (2010) Risperidone and haloperidol promote survival of stem cells in the rat hippocampus. Eur Arch Psychiatry Clin Neurosci (in press)

  28. le Roux CW, Sivakumaran S, Alaghband-Zadeh J, Dhillo W, Kong WM, Wheeler MJ (2002) Free cortisol index as a surrogate marker for serum free cortisol. Ann Clin Biochem 39:406–408

    Article  CAS  PubMed  Google Scholar 

  29. Levite M, Chowers Y, Ganor Y, Besser M, Hershkovits R, Cahalon L (2001) Dopamine interacts directly with its D3 and D2 receptors on normal human T cells, and activates β1 integrin function. Eur J Immunol 31:3504–3512

    Article  CAS  PubMed  Google Scholar 

  30. Maino K, Gruber R, Riedel M, Seitz N, Schwarz M, Müller N (2007) T- and B-lymphocytes in patients with schizophrenia in acute psychotic episode and the course of the treatment. Psychiatry Res 152:173–180

    Article  CAS  PubMed  Google Scholar 

  31. Maxeiner HG, Rojewski MT, Schmitt A, Tumani H, Bechter K, Schmitt M (2009) Flow cytometric analysis of T cell subsets in paired samples of cerebrospinal fluid and peripheral blood from patients with neurological and psychiatric disorders. Brain Behav Immun 23:134–142

    Article  CAS  PubMed  Google Scholar 

  32. Mazzarello V, Cecchini A, Fenu G, Rassu M, Dessy LA, Lorettu L, Montella A (2004) Lymphocytes in schizophrenic patients under therapy: serological, morphological and cell subset findings. Ital J Anat Embryol 109:177–188

    PubMed  Google Scholar 

  33. McAllister CG, Rapaport MH, Pickar D, Podruchny TA, Christison G, Alphs LD, Paul SM (1989) Increased numbers of CD5+ B lymphocytes in schizophrenic patients. Arch Gen Psychiatry 46:890–894

    CAS  PubMed  Google Scholar 

  34. Mian MF, Lauzon NM, Stampfli MR, Mossman KL, Ashkar AA (2008) Impairment of human NK cell cytotoxic activity and cytokine release by cigarette smoke. J Leukoc Biol 83:774–784

    Article  CAS  PubMed  Google Scholar 

  35. Moszczynski P, Zabinski Z, Moszczynski P Jr, Rutowski J, Slowinski S, Tabarowski Z (2001) Immunological findings in cigarette smokers. Toxicol Lett 118:121–127

    Article  CAS  PubMed  Google Scholar 

  36. Müller N, Ackenheil M (1998) Psychoneuroimmunology and the cytokine action in the CNS: implications for psychiatric disorders. Prog Neuropsychopharmacol Biol Psychiatry 22:1–33

    Article  PubMed  Google Scholar 

  37. Müller N, Schwarz MJ (2008) A psychoneuroimmunological perspective to Emil Kraepelins dichotomy: schizophrenia and major depression as inflammatory CNS disorders. Eur Arch Psychiatry Clin Neurosci 258(Suppl 2):97–106

    Article  PubMed  Google Scholar 

  38. Potvin S, Stip E, Sepehry AA, Gendron A, Bah R, Kouassi E (2008) Inflammatory cytokine alterations in schizophrenia: a systematic quantitative review. Biol Psychiatry 63:801–808

    Article  CAS  PubMed  Google Scholar 

  39. Printz DJ, Strauss DH, Goetz R, Sadiq S, Malaspina D, Krolewski J, Gorman JM (1999) Elevation of CD5+ B lymphocytes in schizophrenia. Biol Psychiatry 46:110–118

    Article  CAS  PubMed  Google Scholar 

  40. 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 4:95–104

    Article  CAS  PubMed  Google Scholar 

  41. Riedel M, Spellmann I, Schwarz MJ, Strassnig M, Sikorski C, Möller HJ, Müller N (2007) Decreased T cellular immune response in schizophrenic patients. J Psychiatr Res 41:3–7

    Article  PubMed  Google Scholar 

  42. Rothermundt M, Arolt V, Weitzsch C, Eckhoff D, Kirchner H (1998) Immunological dysfunction in schizophrenia: a systematic approach. Neuropsychobiology 37:186–193

    Article  CAS  PubMed  Google Scholar 

  43. Rudolf S, Schlenke P, Broocks A, Peters M, Rothermundt M, Arolt V, Kirchner H (2004) Search for atypical lymphocytes in schizophrenia. World J Biol Psychiatry 5:33–37

    Article  PubMed  Google Scholar 

  44. Sasaki T, Nanko S, Fukuda R, Kawate T, Kunugi H, Kazamatsuri H (1994) Changes of immunological functions after acute exacerbation in schizophrenia. Biol Psychiatry 35:173–178

    Article  CAS  PubMed  Google Scholar 

  45. Schattner A, Cori Y, Hahn T, Sirota P (1996) No evidence for autoimmunity in schizophrenia. J Autoimmun 9:661–666

    Article  CAS  PubMed  Google Scholar 

  46. Schulz P, Schlotz W (1999) Das Trierer Inventar zur Erfassung von chronischem Streß (TICS): Skalenkonstruktion, teststatistische Überprüfung und Validierung der Skala Arbeitsüberlastung. Diagnostica 45:8–19

    Article  Google Scholar 

  47. Sperner-Unterweger B, Whitworth A, Kemmler G, Hilbe W, Thaler J, Weiss G, Fleischhacker WW (1999) T-cell subsets in schizophrenia: a comparison between drug-naive first episode patients and chronic schizophrenic patients. Schizophr Res 38:61–70

    Article  CAS  PubMed  Google Scholar 

  48. Tanaka S, Matsunaga H, Kimura M, Tatsumi K, Hidaka Y, Takano T, Uema T, Takeda M, Amino N (2003) Autoantibodies against four kinds of neurotransmitter receptors in psychiatric disorders. J Neuroimmunol 141:155–164

    Article  CAS  PubMed  Google Scholar 

  49. Torrey EF, Bartko JJ, Lun ZR, Yolken RH (2006) Antibodies to Toxoplasma gondii in patients with schizophrenia: a meta-analysis. Schizophr Bull 32:200–202

    Google Scholar 

  50. Torrey EF, Leweke MF, Schwarz MJ, Mueller N, Bachmann S, Schroeder J, Dickerson F, Yolken RH (2006) Cytomegalovirus and schizophrenia. CNS Drugs 20:879–885

    Article  PubMed  Google Scholar 

  51. Watanabe Y, Nakayama T, Nagakubo D, Hieshima K, Jin Z, Katou F, Hashimoto K, Yoshie O (2006) Dopamine selectively induces migration and homing of naive CD8+ T cells via dopamine receptor D3. J Immunol 176:848–856

    CAS  PubMed  Google Scholar 

  52. Webster Marketon JI, Glaser R (2008) Stress hormones and immune function. Cell Immunol 252:16–26

    Article  CAS  PubMed  Google Scholar 

  53. Wittchen HU, Zaudig M, Fydrich T (1997) Strukturiertes Klinisches Interview für DSM-IV. Hogrefe, Göttingen

    Google Scholar 

  54. Woods SW (2003) Chlorpromazine equivalent doses for the newer atypical antipsychotics. J Clin Psychiatry 64:663–667

    Article  CAS  PubMed  Google Scholar 

  55. Wüst S, Federenko IS, van Rossum EF, Koper JW, Hellhammer DH (2005) Habituation of cortisol responses to repeated psychosocial stress-further characterization and impact of genetic factors. Psychoneuroendocrinology 30:199–211

    Article  PubMed  Google Scholar 

  56. Yolken RH, Torrey EF (2008) Are some cases of psychosis caused by microbial agents? A review of the evidence. Mol Psychiatry 13:470–479

    Article  CAS  PubMed  Google Scholar 

  57. Young WF (2007) Adrenal medulla, catecholamines, and pheochromocytoma. In: Goldman L, Ausiello D (eds) Cecil medicine, chap 246. Saunders Elsevier, Philadelphia

  58. Yovel G, Sirota P, Mazeh D, Shakhar G, Rosenne E, Ben-Eliyahu S (2000) Higher natural killer cell activity in schizophrenic patients: the impact of serum factors, medication, and smoking. Brain Behav Immun 14:153–169

    Article  CAS  PubMed  Google Scholar 

  59. Zorrilla EP, Luborsky L, McKay JR, Rosenthal R, Houldin A, Tax A, McCorkle R, Seligman DA, Schmidt K (2001) The relationship of depression and stressors to immunological assays: a meta-analytic review. Brain Behav Immun 15:199–226

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported in part by grants of the Saxony-Anhalt Ministry of Research (Grant No. XN3594O/0405M, N2-OGU) and Stanley Medical Research Foundation (Grant No. 07R-1832) to BB and JS. We thank Hendrik Bielau (HB) for his diagnostic re-assessment of schizophrenia cases and are grateful to Henrik Dobrowolny for his skillful assistance in statistical analysis.

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Authors and Affiliations

  1. Department of Psychiatry, University of Magdeburg, Leipziger Strasse 44, 39120, Magdeburg, Germany

    Johann Steiner, Benjamin Panteli, Mareike Brauner, Kolja Schiltz, Tomasz Gos, Martin Walter, Hans-Gert Bernstein & Bernhard Bogerts

  2. Institute of Clinical Immunology and Rheumatology, Hannover Medical School, Hannover, Germany

    Roland Jacobs

  3. Institute of Biotechnology, University of Cambridge, Cambridge, UK

    Sabine Bahn & Marlis Herberth

  4. Institute of Clinical Chemistry and Pathobiochemistry, University of Magdeburg, Magdeburg, Germany

    Sabine Westphal

  5. Institute of Forensic Medicine, Medical University of Gdansk, Gdansk, Poland

    Tomasz Gos

  6. Department of Psychiatry, University of Munich, Munich, Germany

    Aye Mu Myint

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  1. Johann Steiner
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Correspondence to Johann Steiner.

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Steiner, J., Jacobs, R., Panteli, B. et al. Acute schizophrenia is accompanied by reduced T cell and increased B cell immunity. Eur Arch Psychiatry Clin Neurosci 260, 509–518 (2010). https://doi.org/10.1007/s00406-010-0098-x

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