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Plasma kynurenine and related measures in tic disorder patients

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Abstract

Objective

Increased plasma kynurenine has been reported in tic disorder patients, and this observation has been suggested to be indicative of immune dysregulation. In the present study, we examined plasma levels of kynurenine and related molecules in a group of tic disorder patients.

Methods

Plasma concentrations of tryptophan, kynurenine, cortisol, and neopterin were determined in Dutch tic disorder patients (N = 59), and healthy volunteers (N = 32). Group means were compared and age-controlled intra-individual correlations between tic severity and plasma levels of these molecules were examined.

Results

No significant differences were found between patient and control groups in plasma levels of tryptophan, kynurenine, and cortisol concentrations, nor in the kynurenine/tryptophan ratio. However, neopterin was significantly (p = 0.035) higher in patients (mean = 5.13 nmol/l) than in controls (mean = 3.30 nmol/l). Plasma levels of these molecules did not correlate with tic severity, with the exception of tryptophan (r = −0.289, p = 0.049). In patients, plasma neopterin correlated with kynurenine (r = 0.438, p = 0.002); in healthy subjects, tryptophan correlated with kynurenine (r = 0.670, p < 0.001).

Conclusion

While the observed elevation in plasma neopterin is consistent with immune activation in a subset of tic disorder patients, metabolism of tryptophan through the kynurenine pathway appears to be unaltered in tic disorder patients.

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Abbreviations

IDO:

indoleamine 2,3-dioxygenase

K/T ratio:

kynurenine to tryptophan ratio

TDO:

tryptophan 2,3-dioxygenase

References

  1. American Psychiatric Association (1994) Diagnostic and statistical manual of mental disorders, 4th edn. American Psychiatric Press, Washington

    Google Scholar 

  2. Bender DA, Njagi ENM, Danielian PS (1991) Comparison of tryptophan metabolism in vivo and in isolated hepatocytes from vitamin B6 deficient mice. Adv Exp Med Biol 294:359–368

    PubMed  CAS  Google Scholar 

  3. Cardona F, Orefici G (2001) Group A streptococcal infections and tic disorders in an Italian pediatric population. J Pediatr 38(1):71–75

    Google Scholar 

  4. Church AJ, Dale RC, Lees AJ, Giovannoni G, Robertson MM (2003) Tourette’s syndrome: a cross sectional study to examine the PANDAS hypothesis. J Neurol Neurosurg Psychiatry 74(5):602–607

    Article  PubMed  CAS  Google Scholar 

  5. Comings DE (1990) Blood serotonin and tryptophan in Tourette syndrome. Am J Med Genet 36(4):418–430

    Article  PubMed  CAS  Google Scholar 

  6. Dale RC, Candler PM, Church AJ, Wait R, Pocock JM, Giovannoni G (2006a) Neuronal surface glycolytic enzymes are autoantigen targets in post-streptococcal autoimmune CNS disease. J Neuroimmunol 172(1–2):187–197

    Article  CAS  Google Scholar 

  7. Dale RC, Church AJ, Candler PM, Chapman M, Martino D, Giovannoni G (2006b) Serum autoantibodies do not differentiate PANDAS and Tourette syndrome from controls. Neurology 66(10):1612

    Article  CAS  Google Scholar 

  8. Dursun SM, Farrar G, Handley SL, Rickards H, Betts T, Corbett JA (1994) Elevated plasma kynurenine in Tourette syndrome. Mol Chem Neuropathol 21(1):55–60

    Article  PubMed  CAS  Google Scholar 

  9. Gaynor CM, Rickards EHG, Kariyawasam SH, Sidey FM, Robertson MM, Corbett JA (1997) Increased plasma kynurenine in Tourette syndrome may be due to induction of IDO. J Psychopharmacol 11:A23

    Google Scholar 

  10. Gaynor CM, Handley SL (2001) Effects of nicotine on head-shakes and tryptophan metabolites. Psychopharmacology (Berl.) 153(3):327–333

    Article  CAS  Google Scholar 

  11. Heyes MP, Brew BJ, Saito K, Quearry BJ, Price RW, Lee K, Bhalla RB, Der M, Markey SP (1992) Inter-relationships between quinolinic acid, neuroactive kynurenines, neopterin and β2 microglobulin in cerebrospinal fluid and serum of HIV-1-infected patients. J Neuroimmunol 40(1):71–80

    Article  PubMed  CAS  Google Scholar 

  12. Hoekstra PJ, Anderson GM, Limburg PC, Korf J, Kallenberg CG, Minderaa RB (2004a) Neurobiology and neuroimmunology of Tourette’s syndrome: an update. Cell Mol Life Sci 61(7–8):886–898

    CAS  Google Scholar 

  13. Hoekstra PJ, Steenhuis MP, Troost PW, Korf J, Kallenberg CG, Minderaa RB (2004b) Relative contribution of attention-deficit hyperactivity disorder, obsessive-compulsive disorder, and tic severity to social and behavioural problems in tic disorders. J Dev Behav Pediatr 25(4):272–279

    Article  Google Scholar 

  14. Hoekstra PJ, Minderaa RB (2005) Tic disorders and obsessive-compulsive disorder: is autoimmunity involved? Int Rev Psychiatry 17(6):497–502

    Article  PubMed  Google Scholar 

  15. Kirvan CA, Swedo SE, Kurahara D, Cunningham MW (2006) Streptococcal mimicry and antibody-mediated cell signaling in the pathogenesis of Sydenham’s chorea. Autoimmunity 39(1):21–29

    Article  PubMed  CAS  Google Scholar 

  16. Kurlan R (2004) The PANDAS hypothesis: losing its bite? Mov Disord 19(4):371–374

    Article  PubMed  Google Scholar 

  17. Leckman JF, Anderson GM, Cohen DJ, Ort S, Harcherik DF, Hoder EL, Shaywitz BA (1984) Whole blood serotonin and tryptophan levels in Tourette’s disorder: effects of acute and chronic clonidine treatment. Life Sci 35(25):2497–2503

    Article  PubMed  CAS  Google Scholar 

  18. Leckman JF, Riddle MA, Hardin MT, Ort SI, Swartz KL, Stevenson J, Cohen DJ (1989) The Yale Global Tic Severity Scale: initial testing of a clinician-rated scale of tic severity. J Am Acad Child Adolesc Psychiatry 28(4):566–573

    Article  PubMed  CAS  Google Scholar 

  19. Lepage N, McDonald N, Dallaire L, Lambert M (1997) Age-specific distribution of plasma amino acid concentrations in a healthy pediatric population. Clin Chem 43(12):2397–2402

    PubMed  CAS  Google Scholar 

  20. Luo F, Leckman JF, Katsovich L, Findley D, Grantz H, Tucker DM, Lombroso PJ, King RA, Bessen DE (2004) Prospective longitudinal study of children with tic disorders and/or obsessive-compulsive disorder: relationship of symptom exacerbations to newly acquired streptococcal infections. Pediatrics 113(6):e578–e585

    Article  PubMed  Google Scholar 

  21. Maes M, Verkerk R, Bonaccorso S, Ombelet W, Bosmans E, Scharpe S (2002) Depressive and anxiety symptoms in the early puerperium are related to increased degradation of tryptophan into kynurenine, a phenomenon which is related to immune activation. Life Sci 71(16):1837–1848

    Article  PubMed  CAS  Google Scholar 

  22. McCreary AC, Handley SL (1995) Kynurenine potentiates the DOI headshake in mice. J Psychopharmacol 9:68–69

    Google Scholar 

  23. Mell LK, Davis RL, Owens D (2005) Association between streptococcal infection and obsessive-compulsive disorder, Tourette’s syndrome, and tic disorder. Pediatrics 116(1):56–60

    Article  PubMed  Google Scholar 

  24. Millner MM, Franthal W, Thalhammer GH, Berghold A, Aigner RM, Fuger GF, Reibnegger G (1998) Neopterin concentrations in cerebrospinal fluid and serum as an aid in differentiating central nervous system and peripheral infections in children. Clin Chem 44(1):161–167

    PubMed  CAS  Google Scholar 

  25. Muller N, Riedel M, Straube A, Gunther W, Wilske B (2000) Increased anti-streptococcal antibodies in patients with Tourette’s syndrome. Psychiatry Res 94(1):43–49

    Article  PubMed  CAS  Google Scholar 

  26. Murphy TK, Goodman WK, Ayoub EM, Voeller KK (2000) On defining Sydenham’s chorea: where do we draw the line? Biol Psychiatry 47(10):851–857

    Article  PubMed  CAS  Google Scholar 

  27. Peterson BS, Leckman JF, Tucker D, Scahill L, Staib L, Zhang H, King R, Cohen DJ, Gore JC, Lombroso P (2000) Preliminary findings of antistreptococcal antibody titers and basal ganglia volumes in tic, obsessive-compulsive, and attention deficit/hyperactivity disorders. Arch Gen Psychiatry 57(4):364–372

    Article  PubMed  CAS  Google Scholar 

  28. Rickards H, Dursun SM, Farrar G, Betts T, Corbett JA, Handley SL (1996) Increased plasma kynurenine and its relationship to neopterin and tryptophan in Tourette’s syndrome. Psychol Med 26(4):857–862

    Article  PubMed  CAS  Google Scholar 

  29. Schennach H, Murr C, Gachter E, Mayersbach P, Schonitzer D, Fuchs D (2002) Factors influencing serum neopterin concentrations in a population of blood donors. Clin Chem 48(4):643–645

    PubMed  CAS  Google Scholar 

  30. Singer HS, Hong JJ, Yoon DY, Williams PN (2005) Serum autoantibodies do not differentiate PANDAS and Tourette syndrome from controls. Neurology 65(11):1701–1717

    Article  PubMed  CAS  Google Scholar 

  31. Swedo SE, Leonard HL, Garvey M, Mittleman B, Allen AJ, Perlmutter S, Lougee L, Dow S, Zamkoff J, Dubbert BK (1998) Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases. Am J Psychiatry 155(2):264–271

    PubMed  CAS  Google Scholar 

  32. Waldrep DA (2002) Two cases of ADHD following GABHS infection: a PANDAS subgroup? J Am Acad Child Adolesc Psychiatry 41(11):1273–1274

    Article  PubMed  Google Scholar 

  33. Walker KG, Lawrenson J, Wilmshurst JM (2005) Neuropsychiatric movement disorders following streptococcal infection. Dev Med Child Neurol 47(11):771–775

    Article  PubMed  CAS  Google Scholar 

  34. Widner B, Werner ER, Schennach H, Wachter H, Fuchs D (1997) Simultaneous measurement of serum tryptophan and kynurenine by HPLC. Clin Chem 43(12):2424–2426

    PubMed  CAS  Google Scholar 

  35. Widner B, Laich A, Sperner-Unterweger B, Ledochowski M, Fuchs D (2002) Neopterin production, tryptophan degradation, and mental depression-What is the link? Brain, Behav Immun 16(5):590–595

    Article  CAS  Google Scholar 

  36. Yamazaki F, Kuroiwa T, Takikawa T, Kido R (1985) Human indoleamine 2,3 dioxygenase, its tissue distribution, and characterization of the placental enzyme. Biochem J 230(3):635–638

    PubMed  CAS  Google Scholar 

  37. Yasui H, Takai K, Yoshida R, Hayaishi O (1986) Interferon enhances tryptophan metabolism by inducing pulmonary indoleamine 2,3-dioxygenase: its possible occurrence in cancer patients. Proc Natl Acad Sci U S A 83(17):6622–6626

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Psychiatry, University Medical Center Groningen, University of Groningen, P.O. Box 660, 9700 AR, Groningen, The Netherlands

    Pieter J. Hoekstra, Pieter W. Troost & Ruud B. Minderaa

  2. Yale Child Study Center, 230 South Frontage Road, New Haven, CT, 06520, USA

    George M. Anderson

  3. Department of Clinical Immunology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands

    Cees G. M. Kallenberg

Authors
  1. Pieter J. Hoekstra
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  2. George M. Anderson
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  3. Pieter W. Troost
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  4. Cees G. M. Kallenberg
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  5. Ruud B. Minderaa
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Correspondence to Pieter J. Hoekstra.

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Hoekstra, P.J., Anderson, G.M., Troost, P.W. et al. Plasma kynurenine and related measures in tic disorder patients. Eur Child Adolesc Psychiatry 16 (Suppl 1), 71–77 (2007). https://doi.org/10.1007/s00787-007-1009-1

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