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Can BDNF and IL-2 be indicators for the diagnosis in schizophrenic patients with depressive symptoms?

Published online by Cambridge University Press:  27 May 2014

Salih Saygin Eker*
Affiliation:
Department of Psychiatry, Uludag University Medical Faculty, Bursa, Turkey
Ebru Oztepe Yavasci
Affiliation:
Department of Psychiatry, Uludag University Medical Faculty, Bursa, Turkey
Sengul Cangur
Affiliation:
Department of Biostatistics, Duzce University Medical Faculty, Duzce, Turkey
Selcuk Kirli
Affiliation:
Department of Psychiatry, Uludag University Medical Faculty, Bursa, Turkey
Emre Sarandol
Affiliation:
Department of Biochemistry, Uludag University Medical Faculty, Bursa, Turkey
*
Salih Saygin Eker, Uludag University Medical Faculty, Department of Psychiatry, Bursa, Turkey. Tel: 90.224.2951840; Fax: 90.224.4428852; E-mail: saygineker@yahoo.com

Abstract

Objective

The aim of the current study is to determine whether serum levels of brain-derived neurotrophic factor (BDNF) and interleukin-2 (IL-2) can be biological indicators for the diagnosis of schizophrenia in patients with depressive symptoms.

Method

Forty-seven patients (11 patients diagnosed with schizophrenia, 16 patients diagnosed with schizophrenia and comorbid depression and 20 patients diagnosed with major depressive disorder) and 20 healthy subjects were enrolled. The Positive and Negative Symptoms Scale, the Calgary Depression Scale for Schizophrenia and the Hamilton Depression Rating Scale were used for assessment. The serum BDNF and IL-2 levels of all the subjects were studied.

Results

Decreased levels of serum BDNF and increased levels of serum IL-2 were found in the patients diagnosed with either schizophrenia, schizophrenia with depression, or major depressive disorder (p = 0.049, p = 0.010; p = 0.001 and p = 0.044; p = 0.027, p = 0.003; respectively) compared with control group. There were no significant differences between the patient groups in their serum BDNF and IL-2 levels.

Conclusions

The present study suggests that neurotrophic factors and immune system changes are involved in the pathogenesis of schizophrenia with or without depressive symptomatology. However, the data do not clarify whether depressive symptoms in schizophrenia occur as a dimension of schizophrenia or as symptoms of major depression that is comorbid with schizophrenia.

Type
Original Articles
Copyright
Copyright © Scandinavian College of Neuropsychopharmacology 2014 

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References

1.Leff, J. Depressive symptoms in the course of schizophrenia. In: Delusi, LE, editor. Depression in schizophrenia. Washington, DC: American Psychiatric Press, 1990;323.Google Scholar
2.Leff, J, Tress, K, Edwards, B. The clinical course of depressive symptoms in schizophrenia. Schizophr Res 1988;1:2530.Google Scholar
3.Peralta, V, Cuesta, MJ. How many and which are the psychopathological dimensions in schizophrenia? Issues influencing their ascertainment. Schizophr Res 2001;49:269285.Google Scholar
4.Buckley, PF, Mahadik, S, Pillai, A, Terry, A. Neurotrophins and schizophrenia. Schizophr Res 2007;94:111.CrossRefGoogle ScholarPubMed
5.Lee, BH, Kim, H, Park, SH, Kim, YK. Decreased plasma BDNF level in depressive patients. J Affect Disord 2007;101:239244.Google Scholar
6.Tuglu, C, Kara, SH. Depression, cytokines and immune system. Bull Clin Psychopharmacol 2003;13:142150.Google Scholar
7.Kronfol, Z, Remick, DG. Cytokines and the brain: implications for clinical psychiatry. Am J Psychiatry 2000;157:683694.Google Scholar
8.Krueger, JM. Somnogenic activity of immune response modifiers. Trends Pharmacol Sci 1990;11:122126.Google Scholar
9.Shintani, F, Kanba, S, Maruo, Net al. Serum interleukin-6 in schizophrenic patients. Life Sci 1991;49:661664.Google Scholar
10.Ganguli, R, Yang, Z, Shurin, Get al. Serum interleukin-6 concentration in schizophrenia: elevation associated with duration of illness. Psychiatry Res 1994;51:110.Google Scholar
11.Rapaport, MH, Torrey, EF, Mcallister, CGet al. Increased serum soluble interleukin-2 receptors in schizophrenic monozygotic twins. Eur Arch Psychiatry Clin Neurosci 1993;243:710.Google Scholar
12.Akiyama, K. Serum levels of soluble IL-2 receptor alpha, IL-6 and IL-1 receptor antagonist in schizophrenia before and during neuroleptic administration. Schizophr Res 1999;37:97106.Google Scholar
13.Licinio, J, Seibyl, JP, Altemus, M, Charney, DS, Krsytal, JH. Elevated CSF levels of interleukin-2 in neuroleptic-free schizophrenic patients. Am J Psychiatry 1993;150:14081410.Google Scholar
14.Kim, YK, Kim, L, LEE, MS. Relationships between interleukins, neurotransmitters and psychopathology in drug-free male schizophrenics. Schizophr Res 2000;44:165175.Google Scholar
15.Huang, TL, Lee, CT. Associations between serum brain-derived neurotrophic factor levels and clinical phenotypes in schizophrenia patients. J Psychiatr Res 2006;40:664668.Google Scholar
16.Reis, HJ, Nicolato, R, Barbosa, IG, Teixeria, PH, Romano-Silva, MA, Teixeria, AL. Increased serum levels of brain-derived neurotrophic factor in chronic institutionalized patients with schizophrenia. Neurosci Lett 2008;439:157159.Google Scholar
17.Pirildar, S, Gonul, AS, Taneli, F, Akdeniz, F. Low serum levels of brain-derived neurotrophic factor in patients with schizophrenia do not elevate after antipsychotic treatment. Prog Neuropsychopharmacol Biol Psychiatry 2004;28:709713.Google Scholar
18.Ikeda, Y, Yahatan, ITO Iet al. Low serum levels of brain-derived neurotrophic factor and epidermal growth factor in patients with chronic schizophrenia. Schizophr Res 2008;101:5866.Google Scholar
19.Rizos, EN, Papadopoulou, A, Laskose, et al. Reduced serum BDNF levels in patients with chronic schizophrenic disorder in relapse who were treated with typical or atypical antipsychotics. World J Biol Psychiatry 2010;11:251255.Google Scholar
20.Gama, CS, Andreazza, AC, Kunz, Met al. Serum levels of brain-derived neurotrophic factor in patients with schizophrenia and bipolar disorder. Neurosci Lett 2007;420:4548.Google Scholar
21.Jockers-Scherubl, MC, Danker-Hopfe, H, Mahlberg, Ret al. Brain-derived neurotrophic factor serum concentrations are increased in drug naive schizophrenic patients with chronic cannabis abuse and multiple substance abuse. Neurosci Lett 2004;371:7983.Google Scholar
22.Karege, F, Perret, G, Bondolfi, G, Schwald, M, Bertschy, G, Aubry, JM. Decreased serum brain-derived neurotrophic factor levels in major depressed patients. Psychiatry Res 2002;109:143148.Google Scholar
23.Gonul, AS, Akdeniz, F, Taneli, , Donat, O, Eker, C, Vahip, S. Effect of treatment on serum brain-derived neurotrophic factor levels in depressed patients. Eur Arch Psychiatry Clin Neurosci 2005;255:381386.Google Scholar
24.Aydemir, C, Yalcin, ES, Aksaray, Set al. Brain-derived neurotrophic factor (BDNF) changes in the serum of depressed women. Prog Neuropsychopharmacol Biol Psychiatry 2006;30:12561260.Google Scholar
25.Williams, BW. A structured interview guide for Hamilton Depression Rating Scale. Arch Gen Psychiatry 1988;45:742747.Google Scholar
26.Oksay, SO, Aksaray, G, Kaptanoglu, C, Bal, C. Validity and reliability of the Turkish version of Calgary Depression Scale in schizophrenic patients. Turk Psikiyatri Derg 2000;11:278284.Google Scholar
27.Rizos, EN, Michalopoulou, PG, Siafakas, Net al. Association of serum brain-derived neurotrophic Factor and duration of untreated psychosis in first-episode patients with schizophrenia. Neuropsychobiology 2010;62:8790.Google Scholar
28.Chen, DACWang, J, Wang, Bet al. Decreased levels of serum brain-derived neurotrophic factor in drug-naive first-episode schizophrenia: relationship to clinical phenotypes. Psychopharmacology (Berl) 2009;207:375380.Google Scholar
29.Muller, N, Hofschuster, E, Ackenheil, M, Eckstein, R. T-cells and psychopathology in schizophrenia: relationship to the outcome of neuroleptic therapy. Acta Psychiatr Scand 1993;87:6671.Google Scholar
30.Ganglui, R, Rabin, BS, Belle, SH. Decreased interleukin-2 production in schizophrenic patients. Biol Psychiatry 1989;26:427430.Google Scholar
31.Arolt, V, Rothermundt, M, Wandinger, KP, Kirchner, H. Decreased in vitro production of interferon-gamma and interleukin- 2 in whole blood of patients with schizophrenia during treatment. Mol Psychiatry 2000;5:150158.Google Scholar
32.Frommbergeru, H, Bauer, J, Haselbauer, P, Fraulin, A, Riemann, D, Berger, M. Interleukin-6 plasma levels in depression and schizophrenia: comparison between the acute state and after remission. Eur Arch Psychiatry Clin Neurosci 1997;247:228233.Google Scholar
33.Na, KS, Kim, YK. Monocytic Th1 and Th2 cytokine alterations in the pathophysiology of schizophrenia. Neuropsychobiology 2007;56:5563.Google Scholar
34.Villemain, F, Chatenoud, L, Galinowski, Aet al. Aberrant T cell-immunity in untreated schizophrenic patients: deficient interleukin-2 production. Am J Psychiatry 1989;146:609616.Google Scholar
35.Lin, A, Kenis, G, Bignotti, Set al. The inflammatory response system in treatment-resistant schizophrenia: increased serum interleukin-6. Schizophr Res 1998;32:915.Google Scholar
36.Maes, M, Bocchio, L, Bignotti, Set al. Effects of atypical antipsychotics on the inflammatory response system in schizophrenic patients resistant to treatment with typical neuroleptics. Eur Neuropsychopharmacol 2000;10:119124.Google Scholar
37.Mcallister, CG, Van Kammen, DP, Rehn, TJet al. Increases in CSF levels of interleukin-2 in schizophrenia: effects of recurrence of psychosis and medication status. Am J Psychiatry 1995;152:12911297.Google Scholar
38.Sen, S, Duman, R, Sanacora, G. Serum brain-derived neurotrophic factor, depression, and antidepressant medications: meta-analyses and implications. Biol Psychiatry 2008;64:527532.Google Scholar
39.Maes, M, Bosmans, E, Suy, E, Vandervorst, C, de Jonckheere, C, Raus, J. Immune disturbances during major depression: upregulated expression of interleukin-2 receptors. Neuropsychobiology 1990–1991;24:115120.Google Scholar
40.Anisman, H, Merali, Z, Poulter, MO, Hayley, S. Cytokines as a precipitant of depressive illness: animal and human studies. Curr Pharm Des 2005;11:963972.Google Scholar
41.Pavon, L, Sandoval-Lopez, G, Eugenia, Met al. Th2 cytokine response in major depressive disorder patients before treatment. J Neuroimmunol 2006;172:156165.Google Scholar
42.Brietzke, E, Stertz, L, Fernandes, BSet al. Comparison of cytokine levels in depressed, manic and euthymic patients with bipolar disorder. J Affect Disord 2009;116:214217.Google Scholar
43.Dowlati, Y, Herrmann, N, Swardfager, Wet al. A meta-analysis of cytokines in major depression. Biol Psychiatry 2010;67:446457.Google Scholar
44.Xiong, P, Zeng, Y, Wan, Jet al. The role of NGF and IL-2 serum level in assisting the diagnosis in first episode schizophrenia. Psychiatry Res 2011;189:7276.Google Scholar
45.Esen-Danaci, A, Aydemir, O, Deveci, A, Taneli, F, Taskin, O. Serum brain-derived neurotrophic factor (BDNF) levels in schizophrenic patients with depressive symptoms: a preliminary study. Bull Clin Psychopharmacol 2009;19:236240.Google Scholar
46.Noto, CS, Gadelha, A, Belangero, SIet al. Association of biomarkers and depressive symptoms in schizophrenia. Neurosci Lett 2011;505:282285.Google Scholar
47.Fernandes, BS, Gama, CS, Kaunt-Sant'anna, M, Lobato, MI, Belmonte-de-Abreu, P, Kapcinski, F. Serum brain-derived neurotrophic factor in bipolar and unipolar depression: a potential adjunctive tool for differential diagnosis. J Psychiatric Res 2009;43:12001204.Google Scholar
48.Buckley, PF, Pillai, A, Evans, D, Stirewalt, E, Mahadik, S. Brain derived neurotrophic factor in first-episode psychosis. Schizophr Res 2007;91:15.Google Scholar
49.Zhang, XY, Tan, YL, Zhou, DFet al. Serum BDNF levels weight gain in schizophrenic patients on long-term treatment with antipsychotic. J Psychiatr Res 2007;41:9971004.Google Scholar
50.Rizos, EN, Rontos, I, Laskos, Eet al. Investigation of serum BDNF levels in drug-naive patients with schizophrenia. Prog Neuro-psychopharmacol Biol Psychiatry 2008;32:13081311.Google Scholar
51.Bus, BA, Tendolkar, I, Franke, Bet al. Serum brain-derived neurotrophic factor: determinants and relationship with depressive symptoms in a community population of middle-aged and elderly people. World J Biol Psychiatry 2012;13:3947.Google Scholar
52.Bus, BA, Molendijk, ML, Penninx, BJet al. Determinants of serum brain-derived neurotrophic factor. Psychoneuroendocrinology 2011;36:228239.Google Scholar
53.Lee, AH, Lange, C, Ricken, R, Hellweg, R, Lang, UE. Reduced brain-derived neurotrophic factor serum concentrations in acute schizophrenic patients increase during antipsychotic treatment. J Clin Psychopharmacol 2011;31:334336.Google Scholar
54.Xiu, MH, Hui, L, Dang, YFet al. Decreased serum BDNF levels in chronic institutionalized schizophrenia on long-term treatment with typical and atypical antipsychotics. Prog Neuropsychopharmacol Biol Psychiatry 2009;33:15081512.Google Scholar
55.Sozeri-Varma, G, Enli, Y, Toker-Ugurlu, Tet al. Decreased serum BDNF levels in major depressive patients. Neurology Psychiatry and Brain Res 2011;17:8488.Google Scholar
56.Haack, M, Hinze-Selch, T, Fenzel, Tet al. Plasma levels of cytokines and soluble cytokine receptors in psychiatric patients upon hospital admission: effects of confounding factors and diagnosis. J Psychiatr Res 1999;33:407418.Google Scholar
57.Erbagci, AB, Herken, H, Koyluogluo, , Yilmaz, N, Tarakcioglu, M. Serum IL-1b, sIL-2R, IL-6, IL-8 and TNF-a in schizophrenic patients, relation with symptomatology and responsiveness to risperidone treatment. Mediators Inflamm 2001;10:109115.Google Scholar
58.Mahendran, R, Mahendran, R, Chan, YH. Interleukin-2 levels in chronic schizophrenia patients. Ann Acad Med Singapore 2004;33:320323.Google Scholar
59.Bresee, C, Rapaport, MH. Persistently increased serum soluble interleukin-2 receptors in continuously ill patients with schizophrenia. Int J Neuropsychopharmacol 2009;12:861865.Google Scholar
60.Eller, T, Aluoja, A, Maroni, E, Vasar, V. Soluble interleukin-2 receptor and tumor necrosis factor levels in depressed patients in Estonia. Medicina (Kaunas) 2009;45:971977.Google Scholar
61.Maes, M, Meltzer, H, Bosmans, Eet al. Increased plasma concentrations of interleukin-6, soluble interleukin-6 receptor, soluble interleukin-2 receptor and transferrin receptor in major depression. J Affect Disord 1995;34:301309.Google Scholar
62.Akiyama, K. Serum levels of soluble IL-2 receptor alpha, IL-6 and IL-1 receptor antagonist in schizophrenia before and during neuroleptic administration. Schizophr Res 1999;37:97106.Google Scholar
63.Lanquillon, S, Krieg, JC, Benning-Abu-Sach, U, Vedder, H. Cytokine production and treatment response in major depressive disorder. Neuropsychopharmacology 2000;22:370379.Google Scholar
64.Jezierski, MK, Sohrabji, F. Region- and peptide-specific regulation of the neurotrophins by estrogen. Brain Res Mol Brain Res 2000;85:7784.Google Scholar
65.Sohrabji, F, Lewis, DK. Estrogen-BDNF interactions: implications for neurodegenerative diseases. Front Neuroendocrinol 2006;27:404414.Google Scholar
66.Piccinni, A, Marazziti, D, Del, DAet al. Diurnal variation of plasma brain derived neurotrophic factor (BDNF) in humans: an analysis of sex differences. Chronobiol Int 2008;25:819826.Google Scholar