nach oben

European Archives of Psychiatry and Clinical Neuroscience

Erschienen in:

01.10.2008 | ORIGINAL PAPER

Association study of interleukin 2 (IL2) and IL4 with schizophrenia in a Japanese population

verfasst von: Yuichiro Watanabe, Ayako Nunokawa, Masako Shibuya, Naoshi Kaneko, Hiroyuki Nawa, Toshiyuki Someya

Erschienen in: European Archives of Psychiatry and Clinical Neuroscience | Ausgabe 7/2008

Einloggen, um Zugang zu erhalten

Abstract

Interleukin 2 (IL-2) and IL-4 are pleiotropic cytokines regulating Th1/Th2 balance and have a regulatory activity in brain function. Thus these cytokines have been implicated in the pathophysiology of schizophrenia. The latest studies provided controversial results regarding the genetic associations of these cytokines. The functional polymorphisms, IL2-330T/G and IL4-590C/T, were associated with schizophrenia in a German population, although contradictory findings were also reported in a Korean population. To ascertain whether IL2 and IL4 contribute to vulnerability to schizophrenia, we conducted a moderate-scale case-control (536 patients and 510 controls) association study for seven polymorphisms in Japanese subjects. There were no significant associations of these genes with schizophrenia using either single marker or haplotype analyses. The present study suggests that IL2 and IL4 do not contribute to vulnerability to schizophrenia in the Japanese population.

Arolt V, Rothermundt M, Wandinger K-P, Kirchner H (2000) Decreased in vitro production of interferon-gammma and interleukin-2 in whole blood of patients with schizophrenia during treatment. Mol Psychiatry 5:150–158PubMedCrossRef

Avguštin B, Wraber B, Tavčar R (2005) Increased Th₁ and Th₂ immune reactivity with relative Th₂ dominance in patients with acute exacerbation of schizophrenia. Croat Med J 46:268–274PubMed

Barak V, Barak Y, Levine J, Nisman B, Roisman I (1995) Changes in interleukin-1β and soluble interleukin-2 receptor levels in CSF and serum of schizophrenic patients. J Basic Clin Physiol Pharmacol 6:61–69PubMed

Barrett JC, Fry B, Maller J, Daly MJ (2005) Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 21:263–265PubMedCrossRef

Bessler H, Levental Z, Karp L, Modai I, Djaldetti M, Weizman A (1995) Cytokine production in drug-free and neuroleptic-treated schizophrenic patients. Biol Psychiatry 38:297–302PubMedCrossRef

Cazzullo CL, Sacchetti E, Galluzzo A, Panariello A, Adorni A, Pegoraro M, Bosis S, Colombo F, Trabattoni D, Zagliani A, Clerici M (2002) Cytokine profiles in schizophrenic patients treated with risperidone: a 3- month follow-up study. Prog Neuropsychopharmacol Biol Psychiatry 26:33–39PubMedCrossRef

Cazzullo CL, Sacchetti E, Galluzzo A, Panariello A, Colombo F, Zagliani A, Clerici M (2001) Cytokine profiles in drug-naive schizophrenic patients. Schizophr Res 47:293–298PubMedCrossRef

Cazzullo C, Scarone S, Grassi B, Vismara C, Trabattoni D, Clerici M, Clerici M (1998) Cytokines production in chronic schizophrenia patients with or without paranoid behaviour. Prog Neuropsychopharmacol Biol Psychiatry 22:947–957PubMedCrossRef

de Bakker PI, Yelensky R, Pe’er I, Gabriel SB, Daly MJ, Altshuler D (2005) Efficiency and power in genetic association studies. Nat Genet 37:1217–1223PubMedCrossRef

10.

Denicoff KD, Rubinow DR, Papa MZ, Simpson C, Seipp CA, Lotze MT, Chang AE, Rosenstein D, Rosenberg SA (1987) The neuropsychiatric effects of treatment with interleukin-2 and lymphokine-activated killer cells. Ann Intern Med 107:293–300PubMed

11.

Gabriel SB, Schaffner SF, Nguyen H, Moore JM, Roy J, Blumenstiel B, Higgins J, DeFelice M, Lochner A, Faggart M, Liu-Cordero SN, Rotimi C, Adeyemo A, Cooper R, Ward R, Lander ES, Daly MJ, Altshuler D (2002) The structure of haplotype blocks in the human genome. Science 296:2225–2229PubMedCrossRef

12.

Ganguli R, Brar JS, Chengappa KNR, DeLeo M, Yang ZW, Shurin G, Rabin BS (1995) Mitogen-stimulated interleukin-2 production in never-medicated, first-episode schizophrenic patients. Arch Gen Psychiatory 52:668–672

13.

Ganguli R, Rabin BS, Bell SH (1989) Decreased interleukin-2 production in schizophrenic patients. Biol Psychiatry 26:427–430PubMedCrossRef

14.

Gattaz WF, Dalgalarrondo P, Schröder HC (1992) Abnormalities in serum concentrations of interleukin-2, interferon-α and interferon-γ in schizophrenia not detected. Schizophr Res 6:237–241PubMedCrossRef

15.

Hirakawa M, Tanaka T, Hashimoto Y, Kuroda M, Takagi T, Nakamura Y (2002) JSNP: a database of common gene variations in the Japanese population. Nucleic Acids Res 30:158–162PubMedCrossRef

16.

Hoffmann SC, Stanley EM, Cox ED, Craighead N, DiMercurio BS, Koziol DE, Harlan DM, Kirk AD, Blair PJ (2001) Association of cytokine polymorphic inheritance and in vitro cytokine production in anti-CD3/CD28-stimulated peripheral blood lymphocytes. Transplantation 72:1444–1450PubMedCrossRef

17.

Hori H, Yoshimura R, Yamada Y, Ikenouchi A, Mitoma M, Ida Y, Nakamura J (2007) Effects of olanzapine on plasma levels of catecholamine metabolites, cytokines, and brain-derived neurotrophic factor in schizophrenic patients. Int Clin Psychophermacol 22:21–27CrossRef

18.

Hornberg M, Arolt V, Wilke I, Kruse A, Kirchner H (1995) Production of interferones and lymphokines in leukocyte cultures of patients with schizophrenia. Schizophr Res 15:237–242PubMedCrossRef

19.

John S, Turner D, Donn R, Sinnott P, Worthington J, Ollier WER, Hutchinson V, Hajeer AH (1998) Two novel biallelic polymorphisms in the IL-2 gene. Eur J Immunogenet 25: 419–420PubMedCrossRef

20.

Jun T-Y, Lee K-U, Pae C-U, Chae J-H, Bahk W-M, Kim K-S, Han H (2003) Polymorphisms of interleukin-4 promoter and receptor gene for schizophrenia in the Korean population. Psychiatry Clin Neurosci 57:283–288PubMedCrossRef

21.

Kim Y-K, Kim L, Lee M-S (2000) Relationships between interleukins, neurotransmitters and psychopathology in drug-free male schizophrenics. Schizophr Res 44:165–175PubMedCrossRef

22.

Kim YK, Lee MS, Suh KY (1998) Decreased interleukin-2 production in Korean schizophrenic patients. Biol Psychiatry 43:701–704PubMedCrossRef

23.

Kim Y-K, Myint A-M, Lee B-H, Han C-S, Lee H-J, Kim D-J, Leonard BE (2004) Th1, Th2 and Th3 cytokine alteration in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 28:1129–1134PubMedCrossRef

24.

Leykin I, Mayer R, Shinitzky M (1997) Short and long term immunosuppressive effects of clozapine and haloperidol. Immunopharmacology 37:75–86PubMedCrossRef

25.

Licinio J, Seibyl JP, Altemus M, Charney DS, Krystal JH (1993) Elevated CSF levels of interleukin-2 in neuroleptic-free schizophrenic patients. Am J Psychiatry 150:1408–1410PubMed

26.

Lyons A, Downer EJ, Crotty S, Nolan YM, Mills KHG, Lynch MA (2007) CD200 ligand-receptor interaction modulates microglial activation in vivo and in vitro: a role for IL-4. J Neurosci 27:8309–8313PubMedCrossRef

27.

Lyons A, Griffin RJ, Costelloe CE, Clarke RM, Lynch MA (2007) IL-4 attenuates the neuroinflammation induced by amyloid-β in vivo and in vitro. J Neurochem 101:771–781PubMedCrossRef

28.

Mahendran R, Mahendran R, Chan YH (2004) Interleukin-2 levels in chronic schizophrenia patients. Ann Acad Med Singapore 33:320–323PubMed

29.

McAllister CG, van Kammen DP, Rehn TJ, Miller AL, Gurklis J, Kelley ME, Yao J, Peters JL (1995) Increases in CSF levels of interleukin-2 in schizophrenia: effects of recurrence of psychosis and medication status. Am J Psychiatry 152:1291–1297PubMed

30.

Mittleman BB, Castellanos FX, Jacobsen LK, Rapoport JL, Swedo SE, Shearer GM (1997) Cerebrospinal fluid cytokines in pediatric neuropsychiatiric disease. J Immunol 159:2994–2999PubMed

31.

Mosmann TR, Cherwinski H, Bond MW, Giedlin MA, Coffman RL (1986) Two types of murine helper T cell clone. J Immunol 136:2348–2357PubMed

32.

Müller N, Schwarz M (2006) Schizophrenia as an inflammation-mediated dysbalance of glutamatergic neurotransmission. Neurotox Res 10:131–148PubMed

33.

Nawa H, Takahashi M, Patterson PH (2000) Cytokine and growth factor involvement in schizophrenia–support for the developmental model. Mol Psychiatry 5:594–603PubMedCrossRef

34.

Nawa H, Takei N (2006) Recent progress in animal modeling of immune inflammatory processes in schizophrenia: implication of specific cytokines. Neurosci Res 56:2–13PubMedCrossRef

35.

Neale BM, Sham PC (2004) The future of association studies: gene-based analysis and replication. Am J Hum Genet 75:353–362PubMedCrossRef

36.

O’Donnell MC, Catts SV, Ward PB, Liebert B, Lloyd A, Wakefield D, McConaghy N (1996) Increased production of interleukin-2 (IL-2) but not soluble interleukin-2 receptors (sIL-2R) in unmedicated patients with schizophrenia and schizophreniform disorder. Psychiatry Res 65:171–178PubMedCrossRef

37.

Potvin S, Stip E, Sepehry AA, Gendron A, Bah R, Kouassi E (2007) Inflammatory cytokine alterations in schizophrenia: a systematic quantitative review. Biol Psychiatry (in press)

38.

Purcell S, Cherny SS, Sham PC (2003) Genetic power calculator: design of linkage and association genetic mapping studies of complex traits. Bioinformatics 19:149–150PubMedCrossRef

39.

Ramchand R, Wei J, Ramchand CN, Hemmings GP (1994) Increased serum IgE in schizophrenic patients who responded poorly to neuroleptic treatment. Life Sci 54:1579–1584PubMedCrossRef

40.

Rapaport MH, McAllister CG, Pickar D, Tamarkin L, Kirch DG, Paul SM (1997) CSF IL-1 and IL-2 in medicated schizophrenic patients and normal volunteers. Schizophr Res 25:123–129PubMedCrossRef

41.

Rosenwasser LJ, Klemm DJ, Dresback JK, Inamura H, Mascali JJ, Klinnert M, Borish L (1995) Promoter polymorphisms in the chromosome 5 gene cluster in asthma and atopy. Clin Exp Allergy 25:74–78PubMedCrossRef

42.

Rothermundt M, Arolt V, Weitzsch C, Eckhoff D, Kirchner H (1996) Production of cytokines in acute schizophrenic psychosis. Biol Psychiatry 40:1294–1297PubMedCrossRef

43.

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

44.

Schwarz MJ, Krönig H, Riedel M, Dehning S, Douhet A, Spellmann I, Ackenheil M, Möller H-J, Müller N (2006) IL-2 and IL-4 polymorphisms as candidate genes in schizophrenia. Eur Arch Psychiatry Clin Neurosci 256:72–76PubMedCrossRef

45.

Sredni-Kenigsbuch D (2002) TH1/TH2 cytokines in the central nervous system. Int J Neurosci 112:665–703PubMedCrossRef

46.

Tancredi V, Zona C, Velotti F, Eusebi F, Santoni A (1990) Interleukin-2 suppresses established long-term potentiation and inhibits its induction in the rat hippocampus. Brain Res 525:149–151PubMedCrossRef

47.

Theodoropoulou S, Spanakos G, Baxevanis CN, Economou M, Gritzapis AD, Papamichail MP, Stefanis CN (2001) Cytokine serum levels, autologous mixed lymphocyte reaction and surface marker analysis in never medicated and chronically medicated schizophrenic patients. Schizophr Res 47:13–25PubMedCrossRef

48.

Villemain F, Chatenoud L, Galinowski A, Homo-Delarche F, Ginestet D, Loo H, Zarifian E, Bach J-F (1989) Aberrant T cell-mediated immunity in untreated schizophrenic patients: deficient interleukin-2 production. Am J Psychiatry 146:609–616PubMed

49.

Villemain F, Chatenoud L, Guillibert E, Pelicier Y, Bach JF (1987) Decreased production of interleukin-2 in schizophrenia. Ann NY Acad Sci 496:666–675CrossRef

50.

Watanabe Y, Muratake T, Kaneko N, Nunokawa A, Someya T (2006) No association between the brain-derived neurotrophic factor gene and schizophrenia in a Japanese population. Schizophr Res 84:29–35PubMedCrossRef

51.

Wilke I, Arolt V, Rothermundt M, Weitzsch CH, Hornberg M, Kirchner H (1996) Investigations of cytokine production in whole blood cultures of paranoid and residual schizophrenic patients. Eur Arch Psychiatry Clin Neurosci 246:279–284PubMedCrossRef

52.

Xu H-M, Wei J, Hemmings GP (1994) Changes of plasma concentrations of interleukin-1α and interleukin-6 with neuroleptic treatment for schizophrenia. Br J Psychiatry 164:251–253PubMedCrossRef

53.

Zhang XY, Zhou DF, Cao LY, Wu GY, Shen YC (2005) Cortisol and cytokines in chronic and treatment-resistant patients with schizophrenia: association with psychopathology and response to antipsychotics. Neuropsychopharmacology 30:1532–1538PubMedCrossRef

54.

Zhang XY, Zhou DF, Cao LY, Zhang PY, Wu GY, Shen YC (2004) Changes in serum interleukin-2, -6, and -8 levels before and during treatment with risperidone and haloperidol: relationship to outcome in schizophrenia. J Clin Psychiatry 65:940–947PubMedCrossRef

55.

Zhang XY, Zhou DF, Zhang PY, Wu GY, Cao LY, Shen YC (2002) Elevated interleukin-2, interleukin-6 and interleukin-8 serum levels in neuroleptic-free schizophrenia: association with psychopathology. Schizophr Res 57:247–2258PubMedCrossRef

Titel: Association study of interleukin 2 (IL2) and IL4 with schizophrenia in a Japanese population
verfasst von: Yuichiro Watanabe
Ayako Nunokawa
Masako Shibuya
Naoshi Kaneko
Hiroyuki Nawa
Toshiyuki Someya
Publikationsdatum: 01.10.2008
Verlag: D. Steinkopff-Verlag
Erschienen in: European Archives of Psychiatry and Clinical Neuroscience / Ausgabe 7/2008
Print ISSN: 0940-1334
Elektronische ISSN: 1433-8491
DOI: https://doi.org/10.1007/s00406-008-0813-z

Neu im Fachgebiet Psychiatrie

Demenzkranke durch Antipsychotika vielfach gefährdet

23.04.2024 Demenz Nachrichten

Wenn Demenzkranke aufgrund von Symptomen wie Agitation oder Aggressivität mit Antipsychotika behandelt werden, sind damit offenbar noch mehr Risiken verbunden als bislang angenommen.

Weniger postpartale Depressionen nach Esketamin-Einmalgabe

23.04.2024 Depression antepartal oder postpartal Nachrichten

Bislang gibt es kein Medikament zur Prävention von Wochenbettdepressionen. Das Injektionsanästhetikum Esketamin könnte womöglich diese Lücke füllen.

„Psychotherapie ist auch bei sehr alten Menschen hochwirksam!“

22.04.2024 DGIM 2024 Kongressbericht

Die Kombination aus Medikamenten und Psychotherapie gilt als effektivster Ansatz bei Depressionen. Das ist bei betagten Menschen nicht anders, trotz Besonderheiten.

Auf diese Krankheiten bei Geflüchteten sollten Sie vorbereitet sein

22.04.2024 DGIM 2024 Nachrichten

Um Menschen nach der Flucht aus einem Krisengebiet bestmöglich medizinisch betreuen zu können, ist es gut zu wissen, welche Erkrankungen im jeweiligen Herkunftsland häufig sind. Dabei hilft eine Internetseite der CDC (Centers for Disease Control and Prevention).

Update Psychiatrie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 7/2008

5-ht2c receptor and mao-a interaction analysis: no association with suicidal behaviour in bipolar patients

Increased NAA and reduced choline levels in the anterior cingulum following chronic methylphenidate

Executive performance of depressed suicide attempters: the role of suicidal ideation

Predicting caregiver burden in first admission psychiatric patients