Increased levels of IL-6 in the cerebrospinal fluid of patients with chronic schizophrenia - Significance for activation of the kynurenine pathway

Journal of Psychiatry and Neuroscience

Volumn 40, Issue 2, 2015, Pages 126-133

  Schwieler, Lilly ^a   Larsson, Markus K ^a   Skogh, Elisabeth ^b   Kegel, Magdalena E ^a   Orhan, Funda ^a   Abdelmoaty, Sally ^a   Finn, Anja ^a   Bhat, Maria ^a,c   Samuelsson, Martin ^b   Lundberg, Kristina ^b   Dahl, Marja Liisa ^d   Sellgren, Carl ^a   Schuppe Koistinen, Ina ^a,c   Svensson, Camilla I ^a   Erhardt, Sophie ^a   Engberg, Göran ^a  

^a KAROLINSKA INSTITUTE   (Sweden)

^b LINKÖPING UNIVERSITY   (Sweden)

^c SCIENCE FOR LIFE LABORATORY   (Sweden)

^d KAROLINSKA UNIVERSITY HOSPITAL   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

CHOLESTEROL; CYTOKINE; GLUCOSE; INSULIN; INTERLEUKIN 6; KYNURENIC ACID; KYNURENINE; LITHIUM; OLANZAPINE; TRIACYLGLYCEROL; TRYPTOPHAN; ZOPICLONE; IL6 PROTEIN, HUMAN; IL8 PROTEIN, HUMAN; INTERLEUKIN 8;

ADULT; ARTICLE; ASTROCYTE CULTURE; BRIEF PSYCHIATRIC RATING SCALE; CEREBROSPINAL FLUID ANALYSIS; CHEMOLUMINESCENCE; CLINICAL ARTICLE; CONTROLLED STUDY; DSM-IV; FEMALE; GLOBAL ASSESSMENT OF FUNCTIONING; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; HUMAN; LIQUID CHROMATOGRAPHY; MALE; MASS SPECTROMETRY; PHYSICAL EXAMINATION; QUESTIONNAIRE; SCHIZOPHRENIA; YOUNG ADULT; ASTROCYTE; BRAIN CORTEX; CELL CULTURE; CEREBROSPINAL FLUID; CHRONIC DISEASE; METABOLISM; MIDDLE AGED; SECRETION (PROCESS);

ADULT; ASTROCYTES; CELLS, CULTURED; CEREBRAL CORTEX; CHRONIC DISEASE; FEMALE; HUMANS; INTERLEUKIN-6; INTERLEUKIN-8; KYNURENIC ACID; KYNURENINE; MALE; MIDDLE AGED; SCHIZOPHRENIA; TRYPTOPHAN; YOUNG ADULT;

EID: 84923513405     PISSN: 11804882     EISSN: 14882434     Source Type: Journal    
DOI: 10.1503/jpn.140126     Document Type: Article

References (53)

1. Yolken RH, Torrey EF. Are some cases of psychosis caused by microbial agents? A review of the evidence. Mol Psychiatry 2008;13:470-9.
2. Dalman C, Allebeck P, Gunnell D, et al. Infections in the CNS during childhood and the risk of subsequent psychotic illness: a cohort study of more than one million Swedish subjects. Am J Psychiatry 2008;165:59-65.
3. Benros ME, Nielsen PR, Nordentoft M, et al. Autoimmune diseases and severe infections as risk factors for schizophrenia: a 30-year population-based register study. Am J Psychiatry 2011;168:1303-10.
4. Aberg KA, Liu Y, Bukszár J, et al. A comprehensive family-based replication study of schizophrenia genes. JAMA Psychiatry 2013;70:573-81.
5. Doorduin J, de Vries EF, Willemsen AT, et al. Neuroinflammation in schizophrenia-related psychosis: a PET study. J Nucl Med 2009; 50:1801-7.
6. van Berckel BN, Bossong MG, Boellaard R, et al. Microglia activation in recent-onset schizophrenia: a quantitative (R)-[11C] PK11195 positron emission tomography study. Biol Psychiatry 2008;64:820-2.
7. Radewicz K, Garey LJ, Gentleman SM, et al. Increase in HLA-DR immunoreactive microglia in frontal and temporal cortex of chronic schizophrenics. J Neuropathol Exp Neurol 2000;59:137-50.
8. Busse S, Busse M, Schiltz K, et al. Different distribution patterns of lymphocytes and microglia in the hippocampus of patients with residual versus paranoid schizophrenia: Further evidence for disease course-related immune alterations? Brain Behav Immun 2012;26:1273-9.
9. Fillman SG, Cloonan N, Catts VS, et al. Increased inflammatory markers identified in the dorsolateral prefrontal cortex of individuals with schizophrenia. Mol Psychiatry 2013;18:206-14.
10. O’Connor MF, Bower JE, Cho HJ, et al. To assess, to control, to exclude: effects of biobehavioral factors on circulating inflammatory markers. Brain Behav Immun 2009;23:887-97.
11. Potvin S, Stip E, Sepehry AA, et al. Inflammatory cytokine alterations in schizophrenia: a systematic quantitative review. Biol Psychiatry 2008;63:801-8.
12. Miller BJ, Buckley P, Seabolt W, et al. Meta-analysis of cytokine alterations in schizophrenia: clinical status and antipsychotic effects. Biol Psychiatry 2011;70:663-71.
13. Söderlund J, Schröder J, Nordin C, et al. Activation of brain interleukin-1b in schizophrenia. Mol Psychiatry 2009;14:1069-71.
14. Garver DL, Tamas RL, Holcomb JA. Elevated interleukin-6 in the cerebrospinal fluid of a previously delineated schizophrenia subtype. Neuropsychopharmacology 2003;28:1515-20.
15. Sasayama D, Hattori K, Wakabayashi C, et al. Increased cerebrospinal fluid interleukin-6 levels in patients with schizophrenia and those with major depressive disorder. J Psychiatr Res 2013;47:401-6.
16. Asp L, Holtze M, Powell SB, et al. Neonatal infection with neurotropic influenza A virus induces the kynurenine pathway in early life and disrupts sensorimotor gating in adult Tap1-/- mice. Int J Neuropsychopharmacol 2010;13:475-85.
17. Liu X-C, Holtze M, Powell SB, et al. Behavioral disturbances in adult mice following neonatal virus infection or kynurenine treatment - role of brain kynurenic acid. Brain Behav Immun 2014;36:80-9.
18. Schwarcz R, Bruno JP, Muchowski PJ, et al. Kynurenines in the mammalian brain: when physiology meets pathology. Nat Rev Neurosci 2012;13:465-77.
19. Erhardt S, Blennow K, Nordin C, et al. Kynurenic acid levels are elevated in the cerebrospinal fluid of patients with schizophrenia. Neurosci Lett 2001;313:96-8.
20. Schwarcz R, Rassoulpour A, Wu HQ, et al. Increased cortical kynurenate content in schizophrenia. Biol Psychiatry 2001;50:521-30.
21. Nilsson LK, Linderholm KR, Engberg G, et al. Elevated levels of kynurenic acid in the cerebrospinal fluid of male patients with schizophrenia. Schizophr Res 2005;80:315-22.
22. Miller CL, Llenos IC, Dulay JR, et al. Upregulation of the initiating step of the kynurenine pathway in postmortem anterior cingulate cortex from individuals with schizophrenia and bipolar disorder. Brain Res 2006;1073-1074:25-37.
23. Olsson SK, Samuelsson M, Saetre P, et al. Elevated levels of kynurenic acid in the cerebrospinal fluid of patients with bipolar disorder. J Psychiatry Neurosci 2010;35:195-9.
24. Sathyasaikumar KV, Stachowski EK, Wonodi I, et al. Impaired kynurenine pathway metabolism in the prefrontal cortex of individuals with schizophrenia. Schizophr Bull 2011;37:1147-56.
25. Linderholm KR, Skogh E, Olsson SK, et al. Increased levels of kynurenine and kynurenic acid in the CSF of patients with schizophrenia. Schizophr Bull 2012;38:426-32.
26. Olsson SK, Sellgren C, Engberg G, et al. Cerebrospinal fluid kynurenic acid is associated with manic and psychotic features in patients with bipolar I disorder. Bipolar Disord 2012;14:719-26.
27. Josefsson M, Roman M, Skogh E, et al. Liquid chromatography/ tandem mass spectrometry method for determination of olanzapine and N-desmethylolanzapine in human serum and cerebrospinal fluid. J Pharm Biomed Anal 2010;53:576-82.
28. Skogh E, Sjödin I, Josefsson M, et al. High correlation between serum and cerebrospinal fluid olanzapine concentrations in patients with schizophrenia or schizoaffective disorder medicating with oral olanzapine as the only antipsychotic drug. J Clin Psychopharmacol 2011;31:4-9.
29. First MB, Spitzer RI, Gibbon M, et al. Structured Clinical Interview for DMS-IV Axis I Disorders, Clinician Version (SCID-CV). Washington (DC): American Psychiatric Press; 1996.
30. First MB, Spitzer RI, Gibbon M, et al. Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II). Washington (DC): American Psychiatric Press; 1997.
31. Maier B, Laurer H-L, Rose S, et al. Physiological levels of pro-and anti-inflammatory mediators in cerebrospinal fluid and plasma: a normative study. J Neurotrauma 2005;22:822-35.
32. Hori H, Yoshimura R, Yamada Y, et al. Effects of olanzapine on plasma levels of catecholamine metabolites, cytokines, and brain-derived neurotrophic factor in schizophrenic patients. Int Clin Psychopharmacol 2007;22:21-7.
33. Kluge M, Schuld A, Schacht A, et al. Effects of clozapine and olanzapine on cytokine systems are closely linked to weight gain and drug-induced fever. Psychoneuroendocrinology 2009;34:118-28.
34. Carpenter LL, Heninger GR, Malison RT, et al. Cerebrospinal fluid interleukin (IL)-6 in unipolar major depression. J Affect Disord 2004;79:285-9.
35. Martinez JM, Garakani A, Yehuda R, et al. Proinflammatory and “resiliency” proteins in the CSF of patients with major depression. Depress Anxiety 2012;29:32-8.
36. Söderlund J, Olsson SK, Samuelsson M, et al. Elevation of cerebrospinal fluid interleukin-1b in bipolar disorder. J Psychiatry Neurosci 2011;36:114-8.
37. Lindqvist D, Janelidze S, Hagell P, et al. Interleukin-6 is elevated in the cerebrospinal fluid of suicide attempters and related to symptom severity. Biol Psychiatry 2009;66:287-92.
38. McAllister-Sistilli CG, van Kammen DP, Kelley ME, et al. Elevated interleukin-6 in schizophrenia. Psychiatry Res 1999;87:129-36.
39. de Jager W, Bourcier K, Rijkers GT, et al. Prerequisites for cytokine measurements in clinical trials with multiplex immunoassays. BMC Immunol 2009;10:52.
40. Kegel ME, Svensson CI, Erhardt S. IL-1b induces IDO and TDO transcription and provokes the release of kynurenic acid from human astrocytes in vitro. Soc Neurosci Abstr 240.19/E7; 2011.
41. Mándi Y, Vécsei L. The kynurenine system and immunoregulation. J Neural Transm 2012;119:197-209.
42. Kim H, Chen L, Lim G, et al. Brain indoleamine 2,3-dioxygenase contributes to the comorbidity of pain and depression. J Clin Invest 2012;122:2940-54.
43. Miller CL, Llenos IC, Dulay JR, et al. Expression of the kynurenine pathway enzyme tryptophan 2,3-dioxygenase is increased in the frontal cortex of individuals with schizophrenia. Neurobiol Dis 2004;15:618-29.
44. Erhardt S, Olsson SK, Engberg G. Pharmacological manipulation of kynurenic acid: potential in the treatment of psychiatric disorders. CNS Drugs 2009;23:91-101.
45. Erhardt S, Schwieler L, Emanuelsson C, et al. Endogenous kynurenic acid disrupts prepulse inhibition. Biol Psychiatry 2004;56:255-60.
46. Shepard PD, Joy B, Clerkin L, et al. Micromolar brain levels of kynurenic acid are associated with a disruption of auditory sensory gating in the rat. Neuropsychopharmacology 2003;28:1454-62.
47. Chess AC, Landers AM, Bucci DJ. L-kynurenine treatment alters contextual fear conditioning and context discrimination but not cue-specific fear conditioning. Behav Brain Res 2009;201:325-31.
48. Chess AC, Simoni MK, Alling TE, et al. Elevations of endogenous kynurenic acid produce spatial working memory deficits. Schizophr Bull 2007;33:797-804.
49. Pocivavsek A, Wu HQ, Potter MC, et al. Fluctuations in endogenous kynurenic acid control hippocampal glutamate and memory. Neuropsychopharmacology 2011;36:2357-67.
50. Alexander KS, Wu HQ, Schwarcz R, et al. Acute elevations of brain kynurenic acid impair cognitive flexibility: normalization by the alpha7 positive modulator galantamine. Psychopharmacology (Berl) 2012;220:627-37.
51. Kozak R, Campbell BM, Strick CA, et al. Reduction of brain kynurenic acid improves cognitive function. J Neurosci 2014;34:10592-602.
52. Swartz KJ, Matson WR, MacGarvey U, et al. Measurement of kynurenic acid in mammalian brain extracts and cerebrospinal fluid by high-performance liquid chromatography with fluorometric and coulometric electrode array detection. Anal Biochem 1990;185:363-76.
53. Agorastos A, Hauger RL, Barkauskas DA, et al. Circadian rhythmicity, variability and correlation of interleukin-6 levels in plasma and cerebrospinal fluid of healthy men. Psychoneuroendocrinology 2014;44:71-82.