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Cytokine, chemokine and BDNF levels in medication-free pediatric patients with obsessive–compulsive disorder

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Abstract

The aim of this study was to investigate whether the serum levels of IL-12, IL-17, TGFβ, TNF-alpha, sTNFR1, sTNFR2, IL-1β, CCL3, CCL24, CXCL8, and BDNF are associated with obsessive–compulsive disorder (OCD) in medication-free children. A total of 44 (22 boys/22 girls) medication-free children with OCD and 40 (23 boys/17 girls) healthy controls were included in this study. The severity of the OCD symptoms were assessed by the Children’s Yale–Brown Obsessive–Compulsive Scale and the Maudsley Obsessive–Compulsive Inventory. The Children’s Depression Inventory and the Screen for Child Anxiety-Related Emotional Disorders were applied to the children in order to determine depression and anxiety levels. IL-17, IL-12, TGF β, TNF-alpha, sTNFR1, sTNFR2, IL-1β, CCL3, CCL24, CXCL8, and BDNF levels were measured by enzyme-linked immunosorbent assay. Multivariate analysis of covariance (MANCOVA) revealed a significant main effect on both groups for the levels of serum cytokine, chemokine, and BDNF, an effect that was independent of severities of depression and anxiety [Pillai’s Trace V = 0.371, F (11, 70) = 3.756, p < 0.001, hp2 = 0.187]. Analysis of covariance (ANCOVA) indicated that serum TNF-alpha levels were significantly higher in the OCD group than in the control group (p < 0.001). In contrast, serum IL-12 levels were significantly lower in the OCD group than in the control group (p = 0.014). These findings suggest that TNF-alpha and IL-12 may play a role in the pathophysiology of OCD in children. The causal relationship between these proinflammatory cytokines and pediatric OCD requires further investigation.

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References

  1. Bipeta R, Yerramilli SS, Pingali S, Karredla AR, Ali MO (2013) A crosssectional study of insight and family accommodation in pediatric obsessive-compulsive disorder. Child Adolesc Psychiatry Ment Health 7:20

    Article  PubMed  PubMed Central  Google Scholar 

  2. Thomsen PH (2013) Obsessive–compulsive disorders. Eur Child Adolesc Psychiatry 22:23–28

    Article  Google Scholar 

  3. Gray SM, Bloch MH (2012) Systematic review of proinflammatory cytokines in obsessive-compulsive disorder. Curr Psychiatry Rep 14:220–228

    Article  PubMed  PubMed Central  Google Scholar 

  4. Oliveira S, Pelajo C (2010) Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection (PANDAS): a controversial diagnosis. Curr Infect Dis Rep 12:103–109

    Article  PubMed  Google Scholar 

  5. Rocha FF, Correa H, Teixeira AL (2008) Obsessive-compulsive disorder and immunology: a review. Prog Neuropsychopharmacol Biol Psychiatry 32:1139–1146

    Article  PubMed  CAS  Google Scholar 

  6. Mitchell RCB, Goldstein BI (2014) Inflammation in children and adolescents with neuropsychiatric disorders: a systematic review. J Am Acad Child Adolesc Psychiatry 53:274–296

    Article  PubMed  Google Scholar 

  7. Brambilla F, Perna G, Bellodi L, Arancio C, Bertani A, Perini G, Carraro C, Gava F (1997) Plasma interleukin-1β and tumor necrosis factor concentrations in obsessive-compulsive disorders. Biol Psychiatry 42:976–981

    Article  PubMed  CAS  Google Scholar 

  8. Monteleone P, Catapano F, Fabrazzo M, Tortorella A, Maj M (1998) Decreased blood levels of tumor necrosis factor-alpha in patients with obsessive-compulsive disorder. Neuropsychobiology 37:182–185

    Article  PubMed  CAS  Google Scholar 

  9. Denys D, Fluitman S, Kavelaars A, Heijnen C, Westenberg H (2004) Decreased TNF-α and NK activity in obsessive-compulsive disorder. Psychoneuroendocrinology 29:945–952

    Article  PubMed  CAS  Google Scholar 

  10. Konuk N, Tekin IO, Ozturk U, Atik L, Atasoy N, Bektas S, Erdogan A (2007) Plasma levels of tumor necrosis factor-alpha and interleukin-6 in obsessive compulsive disorder. Mediators Inflamm 2007:65704

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  11. Leckman JF, Katsovich L, Kawikova I, Lin H, Zhang H, Krönig H et al (2005) Increasedserum levels of interleukin-12 and tumor necrosis factor-alpha in Tourette’s syndrome. Biol Psychiatry 57:667–673

    Article  PubMed  CAS  Google Scholar 

  12. Matz J, Krause DL, Dehning S, Riedel M, Gruber R, Schwarz MJ, Müller N (2012) Altered monocyte activation markers in Tourette’s syndrome: a case-control study. BMC Psychiatry 12:29

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Bos-Veneman NG, Bijzet J, Limburg PC, Minderaa RB, Kallenberg CG, Hoekstra PJ (2010) Cytokines and soluble adhesion molecules in children and adolescents with a tic disorder. Prog Neuropsychopharmacol Biol Psychiatry 34:1390–1395

    Article  PubMed  CAS  Google Scholar 

  14. Gabbay V, Coffey BJ, Guttman LE, Gottlieb L, Katz Y, Babb JS, Hamamoto MM, Gonzalez CJ (2009) A cytokine study in children and adolescents with Tourette’s disorder. Neuropsychopharmacol Biol Psychiatry 33:967–971

    Article  CAS  Google Scholar 

  15. Şimşek Ş, Gençoğlan S, Yüksel T, Kaplan İ, Alaca R (2016) Cortisol and brain-derived neurotrophic factor levels prior to treatment in children with obsessive-compulsive disorder. J ClinPsychiatry 77:855–859

    Google Scholar 

  16. Kronfol Z, Remick DG (2000) Cytokines and the brain: implications for clinical psychiatry. Am Psychiatry 157:683–694

    Article  CAS  Google Scholar 

  17. Fontenelle LF, Barbosa IG, Luna JV, de Sousa LP, Abreu MN, Teixeira AL (2012) A cytokine study of adult patients with obsessive-compulsive disorder. Compr Psychiatry 53:797–804

    Article  PubMed  Google Scholar 

  18. Liu S, Liu Y, Yin Y, Zhang X, Ma X (2012) A case-control study of interleukin-12 1188A/C polymorphism in obsessive-compulsive disorder in Chinese population. Acta Neuropsychiatr 24:172–175

    Article  PubMed  Google Scholar 

  19. Maes M, Meltzer HY, Bosmans E (1994) Psychoimmune investigation in obsessive-compulsive disorder: assays of plasma transferrin, IL-2 and IL-6 receptor, and IL-1 beta and IL-6 concentrations. Neuropsychobiology 30:57–60

    Article  PubMed  CAS  Google Scholar 

  20. Takatori H, Kanno Y, Chen Z, O’Shea JJ (2008) New complexities in helper T cell fate determination and the implications for autoimmune diseases. Mod Rheumatol 18:533–541

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  21. Kebir H, Kreymborg K, Ifergan I, Dodelet-Devillers A, Cayrol R, Bernard M et al (2007) Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation. Nat Med 13:1173–1175

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Frydecka D, Misiak B, Beszlej JA, Karabon L, Pawlak-Adamska E, Tomkiewicz A, Jonkisz A, Kiejna A (2013) Genetic variants in transforming growth factor-beta gene (TGFB1) affect susceptibility to Schizophrenia. Mol Biol Rep 40:5607–5614

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Davami MH, Baharlou R, Ahmadi Vasmehjani A, Ghanizadeh A, Keshtkar M, Dezhkam I, Atashzar MR (2016) Elevated IL-17 and TGF-β serum levels: a positive correlation between T-helper 17 cell-related pro-inflammatory responses with major depressive disorder. Basic Clin Neurosci 7:137–142

    PubMed  PubMed Central  CAS  Google Scholar 

  24. Li H, Hong W, Zhang C, Wu Z, Wang Z, Yuan C, Li Z, Huang J, Lin Z, Fang Y (2015) IL-23 and TGF-β1 levels as potential predictive biomarkers in treatment of bipolar I disorder with acute manic episode. J Affect Disord 174:361–366

    Article  PubMed  CAS  Google Scholar 

  25. Şimşek Ş, Yüksel T, Çim A, Kaya S (2016) Serum cytokine profiles of children with obsessive-compulsive disorders shows the evidence of autoimmunity. Int J Neuropsychopharmacol 19:1–6

    Article  Google Scholar 

  26. Tokac D, Tuzun E, Gulec H, Yılmaz V, Bireller ES, Cakmakoglu B, Kucukali CI (2016) Chemokine and chemokine receptor polymorphisms in bipolar disorder. Psychiatry Investig 13:541–548

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Han YM, Cheung WK, Wong CK, Sze SL, Cheng TW, Yeung MK, Chan AS (2017) Distinct cytokine and chemokine profiles in autism spectrum disorders. Front Immunol 8:11

    PubMed  PubMed Central  Google Scholar 

  28. Hong S, Lee EE, Martin AS, Soontornniyomkij B, Soontornniyomkij V, Achim CL, Reuter C, Irwin MR, Eyler LT, Jeste DV (2017) Abnormalities in chemokine levels in schizophrenia and their clinical correlates. Schizophr Res 181:63–69

    Article  PubMed  Google Scholar 

  29. Huang EJ, Reichardt LF (2001) Neurotrophins; roles in neuronal development and function. Annu Rev Neurosci 24:677–736

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Karege F, Bondolfi G, Gervasoni N, Schwald M, Aubry JM, Bertschy G (2005) Low brain-derived neurotrophic factor (BDNF) levels in serum of depressed patients probably results from lowered platelet BDNF release unrelated to platelet reactivity. Biol Psychiatry 57:1068–1072

    Article  PubMed  CAS  Google Scholar 

  31. Molendijk ML, Bus BA, Spinhoven P, Penninx BW, Kenis G, Prickaerts J, Voshaar RC, Elzinga BM (2011) Serum levels of brain-derived neurotrophic factor in major depressive disorder: state-trait issues, clinical features and pharmacological treatment. Mol Psychiatry 16:1088–1095

    Article  PubMed  CAS  Google Scholar 

  32. Maina G, Rosso G, Zanardini R, Bogetto F, Gennarelli M, Bocchio-Chiavetto L (2010) Serum levels of brain-derived neurotrophic factor in drug naive obsessive-compulsive patients: a case-control study. J Affect Disord 122:174–178

    Article  PubMed  CAS  Google Scholar 

  33. Wang Y, Mathews CA, Li Y, Lin Z, Xiao Z (2011) Brain-derived neurotrophic factor (BDNF) plasma levels in drug-naïve OCD patients are lower than those in healthy people, but are not lower than those in drug-treated OCD patients. J Affect Disord 133:305–310

    Article  PubMed  CAS  Google Scholar 

  34. Fontenelle LF, Barbosa IG, Luna JV, Rocha NP, Silva Miranda A, Teixeira AL (2012) Neurotrophic factors in obsessive-compulsive disorder. Psychiatry Res 199:195–200

    Article  PubMed  CAS  Google Scholar 

  35. Maes M, Song C, Lin AH, Bonaccorso S, Kenis G, DeJongh R, Bosmans E, Scharpé S (1999) Negative immuno regulatory effects of antidepressants: inhibition of interferon-gamma and stimulation of interleukin-10 secretion. Neuropsychopharmacology 20:370–379

    Article  PubMed  CAS  Google Scholar 

  36. Kenis G, Maes M (2002) Effects of antidepressants on the production of cytokines. Int J Neuropsychopharmacology 5:401–412

    Article  CAS  Google Scholar 

  37. Leonard BE, Myint A (2009) The psychoneuroimmunology of depression. Hum Psychopharmacol 24:165–175

    PubMed  CAS  Google Scholar 

  38. Kaufman J, Birmaher B, Brent D, Rao U, Flynn C, Moreci P, Williamson D, Ryan N (1997) Schedule for affective disorders and schizophrenia for school-age children-present and lifetime version (K-SADS-PL): initial reliability and validity data. J Am Acad Child Adolesc Psychiatry 36:980–988

    Article  PubMed  CAS  Google Scholar 

  39. Gökler B, Ünal F, Pehlivantürk B, Kültür EÇ, Akdemir D, Taner Y (2004) Reliability and validity of schedule for affective disorders and schizophrenia for school age children-present and lifetime version-turkish version (K-SADS-PL-T). Turk J Chıld Adolesc Ment Health 11:109–116

    Google Scholar 

  40. Rachman S, Hodgson RJ (1980) Obsessions and compulsions. Prentice Hall, Englewood Cliffs

    Google Scholar 

  41. Erol N, Savaşır I (1998) Turkish version of Maudsley Obsessive Compulsive Questionnaire. In: paper presented at the meeting of the Turkish National Psychiatry Congress, p 107–114

  42. Hodgson RJ, Rachman S (1977) Obsessional-Compulsive complaints. Behavioral and research. Therapy 15:389–395

    CAS  Google Scholar 

  43. Kovacs M (1985) The Children’s Depression, Inventory (CDI). Psychopharmacol Bull 21:995–998

    PubMed  CAS  Google Scholar 

  44. Oy B (1991) Children’s depression inventory: a study of reliability and validity. Turk Psychiatry Derg 2:137–140

    Google Scholar 

  45. Birmaher B, Brent DA, Chiappetta L, Bridge J, Monga S, Baugher M (1999) Psychometric properties of the Screen for Child Anxiety Related Emotional Disorders (SCARED): a replication study. J Am Acad Child Adolesc Psychiatry 38:1230–1236

    Article  PubMed  CAS  Google Scholar 

  46. Karaceylan F (2005) Reliability and validity of SCARED in Turkish children. Dissertation, Kocaeli University, Kocaeli

    Google Scholar 

  47. Lin H, Katsovich L, Ghebremichael M, Findley DB, Grantz H, Lombroso PJ, King RA, Zhang H, Leckman JF (2007) Psychosocial stress predicts future symptom severities in children and adolescents with Tourette syndrome and/or obsessive-compulsive disorder. J Child Psychol Psychiatry 48(2):157–166

    Article  PubMed  PubMed Central  Google Scholar 

  48. Lo Faravelli C, Sauro C, Godini L, Lelli L, Benni L, Pietrini F, Lazzeretti L, Talamba GA, Fioravanti G, Ricca V (2012) Childhood stressful events, HPA axis and anxiety disorders. World J Psychiatry 2:13–25

    Article  Google Scholar 

  49. Blackmore ER, Moynihan JA, Rubinow DR, Pressman EK, Gilchrist M, O’Connor TG (2011) Psychiatric symptoms and proinflammatory cytokines in pregnancy. Psychosom Med 7:656–663

    Article  CAS  Google Scholar 

  50. Danese A, Pariante CM, Caspi A, Taylor A, Poulton R (2007) Childhood maltreatment predicts adult inflammation in a life-course study. Proc Natl Acad Sci 4:1319–1324

    Article  CAS  Google Scholar 

  51. Shaashua L, Sominsky L, Levi B, Sorski L, Reznick M, Page GG, Ben-Eliyahu S (2012) In vivo suppression of plasma IL-12 levels by acute and chronic stress paradigms: potential mediating mechanisms and sex differences. Brain Behav Immun 26:996–1005

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  52. Dhabhar FS, Saul AN, Holmes TH, Daugherty C, Neri E, Tillie JM, Kusewitt D, Oberyszyn TM (2012) High-anxious individuals show increased chronic stress burden, decreased protective immunity, and increased cancer progression in a mouse model of squamous cell carcinoma. PLoS ONE 7:1–14

    Article  CAS  Google Scholar 

  53. Shaashua L, Rosenne E, Neeman E, Sorski L, Sominsky L, Matzner P, Page GG, Ben-Eliyahu S (2014) Plasma IL-12 levels are suppressed in vivo by stress and surgery through endogenous release of glucocorticoids and prostaglandins but not catecholamines or opioids. Psychoneuroendocrinology 42:11–23

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  54. Ma X (2001) TNF-alpha and IL-12: a balancing act in macrophage functioning. Microbes Infect 3:121–129

    Article  PubMed  CAS  Google Scholar 

  55. Barbosa IG, Huguet RB, Mendonça VA, Sousa LP, Neves FS, Bauer ME, Teixeira AL (2011) Increased plasma levels of soluble TNF receptor I in patients with bipolar disorder. Eur Arch Psychiatry Clin Neurosci 261:139–143

    Article  PubMed  Google Scholar 

  56. Scalzo P, Kummer A, Cardoso F, Teixeira AL (2009) Increased serum levels of soluble tumor necrosis factor-alpha receptor-1 in patients with Parkinson’s disease. J Neuroimmunol 216:122–125

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

We would like to thank our patients and their parents for taking part in this study. Funding for this study was provided by a grant from the Scientific Research Project Coordination Unit of Necmettin Erbakan University (Project No: 161518001).

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Authors and Affiliations

  1. Department of Child and Adolescent Psychiatry, Meram Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey

    Rukiye Çolak Sivri & Ayhan Bilgiç

  2. Department of Biochemistry, Meram Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey

    İbrahim Kılınç

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  1. Rukiye Çolak Sivri
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  2. Ayhan Bilgiç
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Correspondence to Rukiye Çolak Sivri.

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The study was financially supported by Scientific Research Project Coordination Unit of Necmettin Erbakan University (Project No: 161518001).

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Çolak Sivri, R., Bilgiç, A. & Kılınç, İ. Cytokine, chemokine and BDNF levels in medication-free pediatric patients with obsessive–compulsive disorder. Eur Child Adolesc Psychiatry 27, 977–984 (2018). https://doi.org/10.1007/s00787-017-1099-3

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