Hostname: page-component-7c8c6479df-nwzlb Total loading time: 0 Render date: 2024-03-29T09:12:34.090Z Has data issue: false hasContentIssue false

Adjunctive use of interferon γ inducer for treatment of patients with schizophrenia

Published online by Cambridge University Press:  16 November 2015

Tamara Parfenovna Vetlugina*
Affiliation:
Department of Biological Psychiatry and Narcology, Mental Health Research Institute, Tomsk, Russian Federation
Olga Anatolyevna Lobacheva
Affiliation:
Laboratory of Psychoneuroimmunology, Mental Health Research Institute, Tomsk, Russian Federation
Svetlana Alexandrovna Sergeeva
Affiliation:
Open Joint-Stock Company ‘Russian Scientific Center for the Safety of Biologically Active Compounds’, Moscow, Russian Federation
Valentina Borisovna Nikitina
Affiliation:
Laboratory of Psychoneuroimmunology, Mental Health Research Institute, Tomsk, Russian Federation
Tatiana Ivanovna Nevidimova
Affiliation:
Laboratory of Psychoneuroimmunology, Mental Health Research Institute, Tomsk, Russian Federation
Arkady Valentinovich Semke
Affiliation:
Endogenous Disorders Department, Mental Health Research Institute, Tomsk, Russian Federation
*
Professor Tamara P. Vetlugina, Department of Biological Psychiatry and Narcology, Mental Health Research Institute, Tomsk, Russian Federation. Tel: +7 3822 724 415; Fax: +7 3822 724 425; E-mail: vetlug@mail.tomsknet.ru

Abstract

Objective

The present paper is devoted to evaluation of clinical and immunomodulatory effect of ultra-high dilutions of antibodies to human interferon γ, included in the complex therapy of patients with schizophrenia.

Materials and methods

The study was carried out at the Mental Health Research Institute, Tomsk, Russian Federation. This double-blind, placebo-controlled randomised in parallel-group study enrolled 40 patients. As a part of complex therapy, patients from the main group (n=20) received anaferon, a drug containing ultra-high dilutions of affinity-purified antibodies to human interferon γ as the active pharmaceutical ingredient; patients from the comparative group (n=20) received placebo. Duration of the therapy was 30±5 days. Assessment of severity of symptoms and changes in them were made using clinical scales: Positive and Negative Syndrome Scale, Clinical Global Impression, Abnormal Involuntary Movements Scale. Spontaneous and phytohemagglutinin-induced production of interferon γ by immunocompetent cells in supernatants of 48 h whole blood culture of patients was measured by enzyme-linked immunosorbent assay (ELISA) method.

Results

The reduction of interferon-producing potential by immunocompetent cells in comparison with reference normal value was shown in total group of patients (n=40) before combined therapy. During the treatment, increase of spontaneous interferon γ production and favourable changes in psychopathological symptoms as compared with placebo were shown in subjects receiving anaferon. It was found that favourable changes in clinical symptoms assessed using clinical scales with a high degree of confidence correlated with high level of spontaneous interferon γ production.

Conclusion

Anaferon as a part of complex therapy of patients with schizophrenia contributes to enhancement of its efficacy acting via mechanism of psychoimmunomodulation.

Type
Original Articles
Copyright
© Scandinavian College of Neuropsychopharmacology 2015 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Lader, M. Neuroleptic-induced deficit syndrome: old problem, new challenge. J Psychopharmacol 1993;7:392393.Google Scholar
2. Staller, J. The effect of long-term antipsychotic treatment on prolactin. J Child Adolesc Psychopharmacol 2006;16:317326.Google Scholar
3. Műller, N, Riedel, M, Gruber, R, Ackenheil, M, Schwarz, MJ. The immune system and schizophrenia. An integrative view. Ann N Y Acad Sci 2000;917:456467.Google Scholar
4. Strous, RD, Shoenfeld, Y. Schizophrenia, autoimmunity and immune system dysregulation: a comprehensive model updated and revisited. J Autoimmun 2006;27:7180.Google Scholar
5. Műller, N, Schwarz, MJ. Immunology in schizophrenic disorders. Nervenarzt 2007;78:253256. 258–260, 262–263.Google Scholar
6. Vetlugina, TP, Lobacheva, OA, Al'perina, EL et al. Clinical and experimental research of immunomodulatory effect of amisulpride. Vestn Ross Akad Med Nauk 2012;12:1317. (in Russian).Google Scholar
7. Műller, N, Wagner, JK, Krause, D et al. Impaired monocyte activation in schizophrenia. Psychiatry Res 2012;198:341346.Google Scholar
8. Na, KS, Kim, YK. Monocytic, Th1 and Th2 cytokine alterations in the pathophysiology of schizophrenia. Neuropsychobiol 2007;56:5563.Google Scholar
9. Watanabe, Y, Someya, T, Nawa, H. Cytokine hypothesis of schizophrenia pathogenesis: evidence from human studies and animal models. Psychiatry Clin Neurosci 2010;64:217230.Google Scholar
10. Goeb, JL, Cailleau, A, Lainé, P et al. Acute delirium, delusion, and depression during IFN-beta-1a therapy for multiple sclerosis: a case report. Clin Neuropharmacol 2003;26:57.Google Scholar
11. Kalyoncu, OA, Tan, D, Mirsal, H, Pektas, O, Beyazyurek, M. Major depressive disorder with psychotic features induced by interferon-alpha treatment for hepatitis C in a polydrug abuser. J Psychopharmacol 2005;19:102105.Google Scholar
12. Myint, AM, Schwarz, MJ, Steinbusch, HW, Leonard, BE. Neuropsychiatric disorders related to interferon and interleukins treatment. Metab Brain Dis 2009;24:5568.Google Scholar
13. Bell, IR, Koithan, M. A model for homeopathic remedy effects: low dose nanoparticles, allostatic cross-adaptation, and time-dependent sensitization in a complex adaptive system. BMC Complement Altern Med 2012;12:191.Google Scholar
14. Bokhan, NA, Abolonin, AF, Krylov, EN, Vetlugina, TP, Ivanova, SA, Epstein, OI. Comparative efficiency of Proproten-100 during the therapy of patients with alcoholism in the stage of therapeutic remission. Bull Exp Biol Med 2003;135(Suppl. 7):171175.Google Scholar
15. Epstein, ОI, Shtark, МB, Dygay, et al. Pharmacology of ultralow doses of antibodies to endogenous function regulators. Moscow, ID: Publishing House of RAMSci, 2005; (in Russian).Google Scholar
16. Epstein, ОI. Ultralow doses (the story of one study). Moscow, ID: Publishing House of RAMSci, 2008; (in Russian).Google Scholar
17. Kondrat’Eva, EI, Matveeva, LA, Shemyakina, TA, Logvinenko, YUI, Golikova, EV, Kutuzova, EB. The use of anaferon (paediatric formulation) for prophylaxis of acute respiratory viral infections in preschool children. Bull Exp Biol Med 2009;148:266269.Google Scholar
18. Tarasov, SA, Kachanova, MV, Zhavbert, ES, Dugina, YL, Epstein, OI, Sergeeva, SA. Application of ultralow doses of antibodies to interferon-gamma in complex therapy of bacterial infections and prophylaxis of bacterial complications. Bull Exp Biol Med 2009;148:295296.Google Scholar
19. Tarasov, SA, Zarubaev, VV, Gorbunov, EA, Sergeeva, SA, Epstein, OI. Activity of ultra-low doses of antibodies to gamma-interferon against lethal influenza A(H1N1)2009 virus infection in mice. Antiviral Res 2012;93:219224.Google Scholar
20. Vetlugina, TP, Lobacheva, OA, Semke, AV, Sergeeva, SA, Ehpshtejn, OI, Mal’tseva, JL. Method of treating patients with schizophrenia. Ru Patent 2415666 C1 2011. Oficial’nyj bjulleten’ “Federal'nogo instituta promyshlennoj sobstvennosti” “Izobretenija. Poleznye modeli” [Official Bulletin of the Federal Institute of Industrial Property “Inventions. Useful Models”]. 2011; No. 10. http://www1.fips.ru/Archive/PAT/2011FULL/2011.04.10/DOC/RUNWC1/000/000/002/415/666/document.pdf (In Russian).Google Scholar
21. Krasnov, VN, Gurovich, IYA, Mosolov, SN, Shmukler, AB. eds Standards for medical assistance to subjects with schizophrenia. Moscow, ID: Publishing House of Psychiatry Research Institute of Roszdrav, 2006; (in Russian).Google Scholar
22. YK, Kim, Myint, AM, BH, Lee et al. Th1, Th2 and Th3 cytokine alteration in schizophrenia. Prog Neuropsychopharmacol Biol Psychiatry 2004;28:11291134.Google Scholar
23. Steiner, J, Jacobs, R, Panteli, B et al. Acute schizophrenia is accompanied by reduced T cell and increased B cell immunity. Eur Arch Psychiatry Clin Neurosci 2010;260:509518.Google Scholar
24. Reale, M, Patruno, A, De Lutiis, MA et al. Dysregulation of chemo-cytokine production in schizophrenic patients versus healthy controls. BMC Neurosci 2011;25:13 doi: 10.1186/1471-2202-12-13.Google Scholar
25. Epstein, OI. The phenomenon of release activity and the hypothesis of ‘spatial’ homeostasis. Usp Fiziol Nauk 2013;44:5476.Google Scholar
26. Zhu, J, Yamane, H, Paul, WE. Differentiation of effector CD4 T cell populations. Annu Rev Immunol 2010;28:445489.Google Scholar
27. Margolese, HC, Chouinard, G, Kolivakis, TT, Beauclair, L, Miller, R. Tardive dyskinesia in the era of typical and atypical antipsychotics. Part 1: pathophysiology and mechanisms of induction. Can J Psychiatry 2005;50:541547.Google Scholar
28. Yoshida, K, Bies, RR, Suzuki, T et al. Tardive dyskinesia in relation to estimated dopamine D2 receptor occupancy in patients with schizophrenia: analysis of the CATIE data. Schizophr Res 2014;153:184188.Google Scholar
29. HM, An, YL, Tan, Shi, J et al. Altered IL-2, IL-6 and IL-8 serum levels in schizophrenia patients with tardive dyskinesia. Schizophr Res 2015;162:261268.Google Scholar