Title: Assessment the Serum Level of IL6, IL10 versus Neuregulin 1 among Schizophrenic Patients in Iraq

Authors: Dr Manal M. Khadhim, Dr Ali O. Al-Hamzawi, Israa A. Dheeb

 DOI:  https://dx.doi.org/10.18535/jmscr/v5i3.95

Abstract

Background: Schizophrenia is a severe and chronic neuropsychiatric disorder with a lifetime prevalence of about one percent throughout the world. Supporting neuro developmental models, many biological environmental factors are consistently shown to be involved in Schizophrenia development. Relationship of NRG1 and cognition is important to providing a theoretical mechanism to explain NRG1’s potential role in Schizophrenia, it is thought to be associated with disruption of the cytokine milieu and the propensity for the production of proinflammatory cytokines.

Aim: The present study was carried out to investigate the association of selected pro-inflammatory markers (interleukin 6 and 10), and neuregulin 1 in the serum of selected sample of Iraqi patients with schizophrenia.

Methods: Blood samples were collected from participants and were immediately spun and frozen at −20°C. Inflammatory markers were assayed. Serum interleukin10 and 6 was measured by enzyme-linked immunosorbent assay, using Human IL10 &6 ELISA kit with its Components and remarks   (KOMABIO-TECH- INC. Korea). And serum NRG1 were assayed using Human Neuregulin 1 ELISA kit with its Components and Remarks (Bioassay Technology laboratory China).

Result: No important or statistically significant differences in mean age was observed between the 3 study groups. In addition males were more frequent than females in the 3 study groups. Again no statistically significant differences in gender. Significant positive differences that favors cases as compared to both control groups were observed for serum NRG1 and serum IL6, P value= <0.001. IL10 on the other hand showed only a marginal and statistically insignificant increase in cases with schizophrenia when compared to both control groups P value= 0.74.

Conclusion: Schizophrenia is associated with higher serum IL6 and Neuregulin 1 but not IL10 level, than general population

Keywords: Schizophrenia, IL6, IL10, Neuregulin 1.

References

1.      World health organization (WHO).;( 2015).Schizophrenia Fact sheet N°397".  Retrieved3 February 2016.

2.      Owen, M.; Sawa, A. and Mortensen, P.; (2016). "Schizophrenia.". Lancet; Jul 2;388(10039):86-97. 

3.      Sims, A.; (2002). Symptoms in the mind: an introduction to descriptive psycho-athology. Philadelphia: W. B. Saunders.

4.      National Institute of Mental Health (NIMH).;( 2016). Schizophrenia" January.

5.      Van Os, J. and Kapur, S.; (2009)." Schizo-phrenia". Lancet; 374 (9690):635–45.

6.      Picchioni, M. and Murray, R.; (2007). Schizophrenia. BMJ.;335(7610):91–5.

7.      Khandaker, G. ;Pearson, R. ; Zammit, S. ; Lewis, G. and Jones, P. ;( 2014). Association of serum interleukin-6 and c-reactive protein in childhood with depression and psychosis in young adult life: a population-based longitdunal study. JAMA Psychiatry. ;71:1121–28.

8.      Upthegrove, R.; Manzanares, N. and Barnes, N.;( 2014). Cytokine function in medication-naive first episode psychosis: a systematic review and meta-analysis.  Schizophr Res.; 155(1-3): 101–08.

9.      De Witte, L.; Tomasik, J.; Schwarz, E.; et al; (2014). Cytokine alterations in first-episode schizophrenia patients before and after antipsychotic treatment. Schizophr Res. ;154(1-3)::23–29.

10.  Al-Hakeim, H.; Al-Rammahi, D. and Al-Dujaili, A.;( 2015). IL-6, IL-18, sIL-2R, and TNFα proinflammatory markers in depression and schizophrenia patients who are free of overt inflammation. J Affect Disord.; 15;182:106-14.

11.  Tomasik, J.; Rahmoune, H.; Guest, P. and Bahn, S.; (2016). Neuroimmune bioma-rkers in schizophrenia. Schizophr Res.  176 (1):3-13.

12.  Stojanovic, A.; Martorell, L.; Montalvo, I.; et al.;( 2014). Increased serum interleukin-6 levels in early stages of psychosis: associations with at risk mental states and the severity of psychotic symptoms. Psychoneuroendocrinology. ;41:23–32. 

13.  Marín, O.;(2012)."Interneuron dysfunction in psychiatric disorders". Nature Reviews Neuroscience.; 13 (2): 107–20

14.  Lundgaard,I.; Luzhynskaya,A.; Stockley, J.; etal.; (2013). "Neuregulin and BDNF induce a switch to NMDA receptor-depen-dent myelination by oligodendrocytes".  PLoS Biology.; 11(12): e1001743.

15.  Haraldsson, H.; Ettinger, U.; Magnusd-ottir, B.; et al.; (2010).'Neuregulin-1 Genotypes and Eye Movements in Schizophrenia'. Eur Arch Psychiatry Clin Neurosci.; 260: 77-85.

16.  Jessica, L. ; Konasale, M. ; Kodavali ,V. ; et al.;(2012). Genetic Associations betw-een Neuregulin-1 SNPs and Neuroco-gnitive Function in Multigenerational, Multiplex Schizophrenia Families. Psychiatr  Genet.; 22(2): 70–81.

17.  Horacek, J.; Fleg, J.;Tintera, J.; et al.; (2011). Latent toxoplasmosis reduces gray matter density in schizophrenia but not in controls: Voxel-based-morphometry (VBM)  study. World J. Biol. Psychiatry . ; 13(7):501-9.

18.  Na, K.; Jung, H. and Kim, Y.;( 2014). The role of pro-inflammatory cytokines in the neuroinflammation and neurogenesis of schizophrenia. Prog Neuropsychoph-armacol Biol Psychiatry.  3; 48:277-86.

19.  Potvin, S.; Stip, E.; Sepehry, A.; Gendron, A.; Bah, R. and Kouassi, E.;( 2008). Inflammatory cytokine alterations in schizophrenia: a systematic quantitative review. Biol Psychiatry. ; 15;63(8):801-8.

20.  Chiang, S.; Riedel, M.; Schwarz, M. and Mueller, N.;( 2013). Is T-helper type 2 shift schizophrenia-specific? Primary results from a comparison of related psychiatric disorders and healthy controls. Psychiatry Clin Neurosci. ; 67(4):228-36.

21.  Marco D.; Annamaria C.; Nilay H.; et al.;( 2013). Serum and gene expression profile of cytokines in first-episode psychosis. Brain Behav Immun.; 31: 90–95.

22.  Kunz, M.; Cereser, K.; Goi, P.; et al. ;( 2011): Serum levels of IL-6, IL-10 and TNF-alpha in patients with bipolar disorder and schizophrenia: differences in pro- and anti-inflammatory balance. Rev. Bras. Psiquiatr.;33(3):268-274.

23.  Schwarz, M.; Muller, N.; Riedel, M.; et al.;(2001). The Th2-hypothesis of schiz-ophrenia: a strategy to identify a subgroup of schizophrenia caused by immune mechanisms. Med Hypotheses. ; 56:483–6.

24.   Xiu, M.; Yang, G.; Tan, Y.; et al.;( 2014). Decreased interleukin-10 serum levels in first-episode drug-naïve schizophrenia: relationship to psychopathology. Schizophr Res.; 156(1):9-14.

25.  Wang, R.; Wang, Y.; Hu, R.; Chen, X.;  Song, M. and Wang, X.;( 2015). Decre-ased plasma levels of neureglin-1 in drug naïve patients and chronic patients with schizophrenia. Neurosci Lett.;8;606:220-4.

26.  Shibuya, M.; Komi, E.; Wang, R.; et al.;( 2010). Measurement and comparison of serum neuregulin 1 immunoreactivity in control subjects and patients with schizophrenia: an influence of its genetic polymorphism. J Neural Transm (Vienna). 117(7):887-95.

Corresponding Author

Dr Manal M. Khadhim

Assistant Professor, Department of Medical Microbiology, College of Medicine,

University of Al-Qadisiyah, Diwaniyah, Iraq

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