Abstract
Rationale
Over the last 15 years, an increasing body of evidence has suggested a causal relationship between depression and the immunological activation and hypersecretion of pro-inflammatory cytokines, such as interleukin-1, interleukin-6 and tumor necrosis factor-alpha (TNF-α). However, little is known about the probable relationship of serum TNF-α with major depressive disorder (MDD).
Objective
To assess whether serum TNF-α levels could be associated with the clinical course of MDD.
Subjects and methods
TNF-α and C-reactive protein (CRP) serum concentrations, erythrocyte sedimentation rate, and leukocyte count were measured in 26 MDD patients and in 17 controls. The measurements were repeated following 6 weeks of antidepressant treatment with selective serotonin re-uptake inhibitors. Psychopathological improvement and the severity of depression were evaluated with the Hamilton Depression Rating Scale (HAMD) and Beck Depression Inventory (BDI).
Results
On admission, serum TNF-α and leukocyte count were significantly higher in MDD patients compared to controls (P<0.001 and P=0.005, respectively). With the antidepressant treatment, both HAMD and BDI scores decreased significantly (P<0.001 for both). Comparison of pre- and post-treatment measurements revealed that TNF-α, CRP, and leukocyte count decreased to levels comparable with those of the control subjects (P<0.001, P=0.01, and P=0.01, respectively).
Conclusions
The results emphasized that some immunological parameters, such as CRP, leukocyte count and TNF-α, are significantly involved in the clinical course and treatment response in MDD. TNF-α in particular could be considered as a potential state marker in MDD.
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References
Ader R, Cohen N, Felten D (1995) Psychoneuroimmunology: interactions between the nervous system and the immune system. Lancet 345:99–103
Anisman H, Ravindran AV, Griffiths J, Merali Z (1999) Interleukin-1 beta production in dysthymia before and after pharmacotherapy. Biol Psychiatry 46:1649–1655
Beck A (1961) An inventory for measuring depression. Arch Gen Psychiatry 4:561–571
Berk M, Wadee AA, Kuschke RH, O'Neill-Kerr A (1997) Acute phase proteins in major depression. J Psychosom Res 43:529–534
Brambilla F, Maggioni M (1998) Blood levels of cytokines in elderly patients with major depressive disorder. Acta Psychiatr Scand 97:309–313
Capuron L, Dantzer R (2003) Cytokines and depression: the need for a new paradigm. Brain Behav Immun 17:119–124
Castanon N, Bluthe RM, Dantzer R (2001) Chronic treatment with the atypical antidepressant tianeptine attenuates sickness behavior induced by peripheral but not central lipopolysaccharide and interleukin-1beta in the rat. Psychopharmacology 154:50–60
Connor TJ, Leonard BE (1998) Depression, stress and immunological activation: the role of cytokines in depressive disorders. Life Sci 62:583–606
Dantzer R (2001) Cytokine-induced sickness behavior: where do we stand? Brain Behav Immun 15:7–24
Dantzer R, Wollman E, Vitkovic L, Yirmiya R (1999) Cytokines and depression: fortuitous or causative association? Mol Psychiatry 4:328–332
Frommberger UH, Bauer J, Haselbauer P, Fraulin A, Riemann D, Berger M (1997) Interleukin-6 (IL-6) plasma levels in depression and schizophrenia: comparison between the acute state and after remission. Eur Arch Psychiatry Clin Neurosci 247:228–233
Haack M, Hinze-Selch D, Fenzel T, Kraus T, Kuhn M, Schuld A, Pollmacher T (1999) Plasma levels of cytokines and soluble cytokine receptors in psychiatric patients upon hospital admission: effects of confounding factors and diagnosis. J Psychiatr Res 33:407–418
Hamilton M (1960) A rating scale for depression. J Neurol Neurosurg Psychiat 23:56–62
Kelley KW, Bluthe RM, Dantzer R, Zhou JH, Shen WH, Johnson RW, Broussard SR (2003) Cytokine-induced sickness behavior. Brain Behav Immun 17:S112–S118
Konsman JP, Parnet P, Dantzer R (2002) Cytokine-induced sickness behaviour: mechanisms and implications. Trends Neurosci 25:154–159
Kronfol Z, Remick DG (2000) Cytokines and the brain: implications for clinical psychiatry. Am J Psychiatry 157:683–694
Landmann R, Schaub B, Link S, Wacker HR (1997) Unaltered monocyte function in patients with major depression before and after three months of antidepressive therapy. Biol Psychiatry 41:675–681
Lanquillon S, Krieg JC, Bening-Abu-Shach U, Vedder H (2000) Cytokine production and treatment response in major depressive disorder. Neuropsychopharmacology 22:370–379
Leonard BE (2001) The immune system, depression and the action of antidepressants. Prog Neuropsychopharmacol Biol Psychiatry 25:767–780
Maes M, Scharpe S, Van Grootel L, Uyttenbroeck W, Cooreman W, Cosyns P, Suy E (1992) Higher alpha 1-antitrypsin, haptoglobin, ceruloplasmin and lower retinol binding protein plasma levels during depression: further evidence for the existence of an inflammatory response during that illness. J Affect Disord 24:183–192
Maes M, Meltzer HY, Bosmans E, Bergmans R, Vandoolaeghe E, Ranjan R, Desnyder R (1995) Increased plasma concentrations of interleukin-6, soluble interleukin-6, soluble interleukin-2 and transferrin receptor in major depression. J Affect Disord 34:301–309
Maes M, Song C, Lin AH, Bonaccorso S, Kenis G, De Jongh R, Bosmans E, Scharpe S (1999) Negative immunoregulatory effects of antidepressants: inhibition of interferon-gamma and stimulation of interleukin-10 secretion. Neuropsychopharmacology 20:370–379
Maier SF, Watkins LR (1998) Cytokines for psychologists: implications of bidirectional immune-to-brain communication for understanding behavior, mood, and cognition. Psychol Rev 105:83–107
Mikova O, Yakimova R, Bosmans E, Kenis G, Maes M (2001) Increased serum tumor necrosis factor alpha concentrations in major depression and multiple sclerosis. Eur Neuropsychopharmacol 11:203–208
Owen BM, Eccleston D, Ferrier IN, Young AH (2001) Raised levels of plasma interleukin-1beta in major and postviral depression. Acta Psychiatr Scand 103:226–228
Papanicolaou DA, Wilder RL, Manolagas SC, Chrousos GP (1998) The pathophysiologic roles of interleukin-6 in human disease. Ann Int Med 128:127–137
Rothermundt M, Arolt V, Peters M, Gutbrodt H, Fenker J, Kersting A, Kirchner H (2001) Inflammatory markers in major depression and melancholia. J Affect Disord 63:93–102
Seidel A, Arolt V, Hunstiger M, Rink L, Behnisch A, Kirchner H (1996a) Increased CD56+ natural killer cells and related cytokines in major depression. Clin Immunol Immunopathol 78:83–85
Seidel A, Arolt V, Hunstiger M, Rink L, Behnisch A, Kirchner H (1996b) Major depressive disorder is associated with elevated monocyte counts. Acta Psychiatr Scand 94:198–204
Shen Y, Connor TJ, Nolan Y, Kelly JP, Leonard BE (1999) Differential effect of chronic antidepressant treatments on lipopolysaccharide-induced depressive-like behavioural symptoms in the rat. Life Sci 65:1773–1786
Sluzewska A, Rybakowski J, Bosmans E, Sobieska M, Berghmans R, Maes M, Wiktorowicz K (1996a) Indicators of immune activation in major depression. Psychiatry Res 64:161–167
Sluzewska A, Rybakowski JK, Sobieska M, Wiktorowicz K (1996b) Concentration and microheterogeneity glycophorms of alpha-1-acid glycoprotein in major depressive disorder. J Affect Disord 39:149–155
Smith RS (1991) The macrophage theory of depression. Med Hypoth 35:298–306
Song C, Leonard BE (2000) Fundamentals of psychoneuroimmunology. Wiley, Chichester
Song C, Dinan T, Leonard BE (1994) Changes in immunoglobulin, complement and acute phase protein levels in the depressed patients and normal controls. J Affect Disord 30:283–288
Song C, Lin A, Bonaccorso S, Heide C, Verkerk R, Kenis G, Bosmans E, Scharpe S, Whelan A, Cosyns P, De Jongh R, Maes M (1998) The inflammatory response system and the availability of plasma tryptophan in patients with primary sleep disorders and major depression. J Affect Disord 49:211–219
Sorias S, Saygili R, Elbi H, et al (1988) DSM-III-R Yapilandirilmis Klinik Görüsmesi Türkce Versiyonu SCID-I ve SCID-II. Ege Universitesi Matbaasi, Bornova
Watkins LR, Maier SF, Goehler LE (1995) Cytokine-to-brain communication: a review and analysis of alternative mechanisms. Life Sci 57:1011–1026
Xia Z, DePierre JW, Nassberger L (1996) Tricyclic antidepressants inhibit IL-6, IL-1 beta and TNF-alpha release in human blood monocytes and IL-2 and interferon-gamma in T cells. Immunopharmacology 34:27–37
Yirmiya R (1996) Endotoxin produces a depressive-like episode in rats. Brain Res 711:163–174
Yirmiya R, Weidenfeld J, Barak O, Avitsur R, Pollak Y, Gallily R, Wohlman A, Ovadia H, Ben Hur T (1999) The role of brain cytokines in mediating the behavioral and neuroendocrine effects of intracerebral mycoplasma fermentans. Brain Res 829:28–38
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Tuglu, C., Kara, S.H., Caliyurt, O. et al. Increased serum tumor necrosis factor-alpha levels and treatment response in major depressive disorder. Psychopharmacology 170, 429–433 (2003). https://doi.org/10.1007/s00213-003-1566-z
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DOI: https://doi.org/10.1007/s00213-003-1566-z