Abstract
High levels of several proinflammatory components of the immune system, such as interleukin-6, C-reactive protein, tumor necrosis factor (TNF)-α, or neopterin in patients suffering from major depression (MD) point to the involvement of an inflammatory process in the pathophysiology of MD. The direct and indirect effects of cytokines on neurotransmitter storage and release - mediated by microglia cells and astrocytes - are discussed. The tryptophan/kynurenine metabolism is one of the indirect mechanisms because the enzyme indoleamine 2,3-dioxygenase - a key enzyme of this metabolism in the central nervous system - is driven by pro- and anti-inflammatory cytokines and degrades serotonin. Moreover, neuroactive kynurenines such as kynurenic acid and quinolinic acid act on the glutamatergic neurotransmission as N-methyl-D-aspartate antagonists and agonists, respectively. Alterations of the serotonergic, noradrenergic and glutamatergic neurotransmission have been shown with low-level neuroinflammation and may be involved in symptom generation. Epidemiological and clinical studies show a role for inflammation as a risk factor for MD. A large-scale epidemiological study in MD clearly demonstrates that severe infections and autoimmune disorders are lifetime risk factors for MD. The vulnerability-stress-inflammation model matches with this view as stress may increase proinflammatory cytokines and even contribute to a lasting proinflammatory state. Further support comes from the therapeutic benefit of anti-inflammatory medications such as the cyclo-oxygenase-2 inhibitors, TNF-α antagonists and others, and the anti-inflammatory and immunomodulatory intrinsic effects of antidepressants.
References
1.
Maes M: Cytokines in major depression. Biol Psychiatry 1994;36:498-499.
2.
Maes M, Stevens W, DeClerck L, Bridts C, Peeters D, Schotte C, Cosyns P: Immune disorders in depression: higher T helper/T suppressor-cytotoxic cell ratio. Acta Psychiatr Scand 1992;86:423-431.
3.
Müller N, Hofschuster E, Ackenheil M, Mempel W, Eckstein R: Investigations of the cellular immunity during depression and the free interval: evidence for an immune activation in affective psychosis. Prog Neuropsychopharmacol Biol Psychiatry 1993;17:713-730.
4.
Myint AM, Leonard BE, Steinbusch HW, Kim YK: Th1, Th2, and Th3 cytokine alterations in major depression. J Affect Disord 2005;88:167-173.
5.
Rothermundt M, Arolt V, Peters M, Gutbrodt H, Fenker J, Kersting A, Kirchner H: Inflammatory markers in major depression and melancholia. J Affect Disord 2001;63:93-102.
6.
Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctot KL: A meta-analysis of cytokines in major depression. Biol Psychiatry 2010;67:446-457.
7.
Howren MB, Lamkin DM, Suls J: Associations of depression with C-reactive protein, IL-1, and IL-6: a meta-analysis. Psychosom Med 2009;71:171-186.
8.
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: The inflammatory response system and the availability of plasma tryptophan in patients with primary sleep disorders and major depression. J Affect Disord 1998;49:211-219.
9.
Calabrese JR, Skwerer RG, Barna B, Gulledge AD, Valenzuela R, Butkus A, Subichin S, Krupp NE: Depression, immunocompetence, and prostaglandins of the E series. Psychiatry Res 1986;17:41-47.
10.
Linnoila M, Whorton AR, Rubinow DR, Cowdry RW, Ninan PT, Waters RN: CSF prostaglandin levels in depressed and schizophrenic patients. Arch Gen Psychiatry 1983;40:405-406.
11.
Nishino S, Ueno R, Ohishi K, Sakai T, Hayaishi O: Salivary prostaglandin concentrations: possible state indicators for major depression. Am J Psychiatry 1989;146:365-368.
12.
Ohishi K, Ueno R, Nishino S, Sakai T, Hayaishi O: Increased level of salivary prostaglandins in patients with major depression. Biol Psychiatry 1988;23:326-334.
13.
Brambilla R, Bracchi-Ricard V, Hu WH, Frydel B, Bramwell A, Karmally S, Green EJ, Bethea JR: Inhibition of astroglial nuclear factor κB reduces inflammation and improves functional recovery after spinal cord injury. J Exp Med 2005;202:145-156.
14.
Farina C, Aloisi F, Meinl E: Astrocytes are active players in cerebral innate immunity. Trends Immunol 2007;28:138-145.
15.
Gao HM, Hong JS: Why neurodegenerative diseases are progressive: uncontrolled inflammation drives disease progression. Trends Immunol 2008;29:357-365.
16.
Aronica E, Gorter JA, Ijlst-Keizers H, Rozemuller AJ, Yankaya B, Leenstra S, Troost D: Expression and functional role of mGluR3 and mGluR5 in human astrocytes and glioma cells: opposite regulation of glutamate transporter proteins. Eur J Neurosci 2003;17:2106-2118.
17.
Wildemann B, Oschmann P, Reiber H: Laboratory Diagnosis in Neurology. Stuttgart, Thieme, 2010.
18.
Schwartz M, Shechter R: Protective autoimmunity functions by intracranial immunosurveillance to support the mind: the missing link between health and disease. Mol Psychiatry 2010;15:342-354.
19.
Hampel H, Muller SF, Berger C, Haberl A, Ackenheil M, Hock C: Evidence of blood-cerebrospinal fluid-barrier impairment in a subgroup of patients with dementia of the Alzheimer type and major depression: a possible indicator for immunoactivation. Dementia 1995;6:348-354.
20.
Hampel H, Kotter HU, Moller HJ: Blood-cerebrospinal fluid barrier dysfunction for high molecular weight proteins in Alzheimer disease and major depression: indication for disease subsets. Alzheimer Dis Assoc Disord 1997;11:78-87.
21.
Hampel H, Kotter HU, Padberg F, Korschenhausen DA, Moller HJ: Oligoclonal bands and blood: cerebrospinal-fluid barrier dysfunction in a subset of patients with Alzheimer disease: comparison with vascular dementia, major depression, and multiple sclerosis. Alzheimer Dis Assoc Disord 1999;13:9-19.
22.
Bechter K, Reiber H, Herzog S, Fuchs D, Tumani H, Maxeiner HG: Cerebrospinal fluid analysis in affective and schizophrenic spectrum disorders: identification of subgroups with immune responses and blood-CSF barrier dysfunction. J Psychiatr Res 2010;44:321-330.
23.
Maxeiner HG, Rojewski MT, Schmitt A, Tumani H, Bechter K, Schmitt M: Flow cytometric analysis of T cell subsets in paired samples of cerebrospinal fluid and peripheral blood from patients with neurological and psychiatric disorders. Brain Behav Immun 2009;23:134-142.
24.
Kuehne LK, Reiber H, Bechter K, Hagberg L, Fuchs D: Cerebrospinal fluid neopterin is brain-derived and not associated with blood CSF barrier dysfunction in non-inflammatory affective and schizophrenic spectrum disorders. J Psychiatr Res 2013;47:1417-1422.
25.
Dantzer R: Cytokine-induced sickness behavior: where do we stand? Brain Behav Immun 2001;15:7-24.
26.
Dantzer R, O'Connor JC, Freund GG, Johnson RW, Kelley KW: From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci 2008;9:46-56.
27.
Reichenberg A, Yirmiya R, Schuld A, Kraus T, Haack M, Morag A, Pollmacher T: Cytokine-associated emotional and cognitive disturbances in humans. Arch Gen Psychiatry 2001;58:445-452.
28.
Reichenberg A, Kraus T, Haack M, Schuld A, Pollmacher T, Yirmiya R: Endotoxin-induced changes in food consumption in healthy volunteers are associated with TNF-α and IL-6 secretion. Psychoneuroendocrinology 2002;27:945-956.
29.
Lanquillon S, Krieg JC, Bening-Abu-Shach U, Vedder H: Cytokine production and treatment response in major depressive disorder. Neuropsychopharmacology 2000;22:370-379.
30.
Häfner S, Baghai TC, Eser D, Schüle C, Rupprecht R, Bondy B, Bedarida G, von SC: C-reactive protein is associated with polymorphisms of the angiotensin-converting enzyme gene in major depressed patients. J Psychiatr Res 2008;42:163-165.
31.
Danner M, Kasl SV, Abramson JL, Vaccarino V: Association between depression and elevated C-reactive protein. Psychosom Med 2003;65:347-356.
32.
Ford DE, Erlinger TP: Depression and C-reactive protein in US adults: data from the Third National Health and Nutrition Examination Survey. Arch Intern Med 2004;164:1010-1014.
33.
Kling MA, Alesci S, Csako G, Costello R, Luckenbaugh DA, Bonne O, Duncko R, Drevets WC, Manji HK, Charney DS, Gold PW, Neumeister A: Sustained low-grade pro-inflammatory state in unmedicated, remitted women with major depressive disorder as evidenced by elevated serum levels of the acute phase proteins C-reactive protein and serum amyloid A. Biol Psychiatry 2007;62:309-313.
34.
Cizza G, Eskandari F, Coyle M, Krishnamurthy P, Wright EC, Mistry S, Csako G: Plasma CRP levels in premenopausal women with major depression: a 12-month controlled study. Horm Metab Res 2009;41:641-648.
35.
Gimeno D, Marmot MG, Singh-Manoux A: Inflammatory markers and cognitive function in middle-aged adults: the Whitehall II study. Psychoneuroendocrinology 2008;33:1322-1334.
36.
Maes M, Meltzer HY, Bosmans E, Bergmans R, Vandoolaeghe E, Ranjan R, Desnyder R: Increased plasma concentrations of interleukin-6, soluble interleukin-6, soluble interleukin-2 and transferrin receptor in major depression. J Affect Disord 1995;34:301-309.
37.
Maes M, Meltzer HY, Buckley P, Bosmans E: Plasma-soluble interleukin-2 and transferrin receptor in schizophrenia and major depression. Eur Arch Psychiatry Clin Neurosci 1995;244:325-329.
38.
Irwin M: Immune correlates of depression. Adv Exp Med Biol 1999;461:1-24.
39.
Nunes SOV, Reiche EMV, Morimoto HK, Matsuo T, Itano EN, Xavier ECD, Yamashita CM, Vieira VR, Menoli AV, Silva SS, Costa FB, Reiche FV, Silva FLV, Kaminami MS: Immune and hormonal activity in adults suffering from depression. Braz J Med Biol Res 2002;35:581-587.
40.
Müller N, Schwarz MJ: Immunology in anxiety and depression; in Kasper S, den Boer JA, Sitsen JMA (eds): Handbook of Depression and Anxiety. New York, Marcel Dekker, 2002, pp 267-288.
41.
Mikova O, Yakimova R, Bosmans E, Kenis G, Maes M: Increased serum tumor necrosis factor alpha concentrations in major depression and multiple sclerosis. Eur Neuropsychopharmacol 2001;11:203-208.
42.
Herbert TB, Cohen S: Depression and immunity: a meta-analytic review. Psychol Bull 1993;113:472-486.
43.
Seidel A, Arolt V, Hunstiger M, Rink L, Behnisch A, Kirchner H: Major depressive disorder is associated with elevated monocyte counts. Acta Psychiatr Scand 1996;94:198-204.
44.
Rothermundt M, Arolt V, Fenker J, Gutbrodt H, Peters M, Kirchner H: Different immune patterns in melancholic and non-melancholic major depression. Eur Arch Psychiatry Clin Neurosci 2001;251:90-97.
45.
Duch DS, Woolf JH, Nichol CA, Davidson JR, Garbutt JC: Urinary excretion of biopterin and neopterin in psychiatric disorders. Psychiatry Res 1984;11:83-89.
46.
Dunbar PR, Hill J, Neale TJ, Mellsop GW: Neopterin measurement provides evidence of altered cell-mediated immunity in patients with depression, but not with schizophrenia. Psychol Med 1992;22:1051-1057.
47.
Maes M, Scharpe S, Meltzer HY, Okayli G, Bosmans E, D'Hondt P, Vanden Bossche BV, Cosyns P: Increased neopterin and interferon-gamma secretion and lower availability of L-tryptophan in major depression: further evidence for an immune response. Psychiatry Res 1994;54:143-160.
48.
Bonaccorso S, Lin AH, Verkerk R, Van Hunsel F, Libbrecht I, Scharpe S, DeClerck L, Biondi M, Janca A, Maes M: Immune markers in fibromyalgia: comparison with major depressed patients and normal volunteers. J Affect Disord 1998;48:75-82.
49.
Müller N, Myint AM, Schwarz MJ: Inflammatory biomarkers and depression. Neurotox Res 2011;19:308-318.
50.
Maes M: Depression is an inflammatory disease, but cell-mediated immune activation is the key component of depression. Prog Neuropsychopharmacol Biol Psychiatry 2011;35:664-675.
51.
Benros ME, Waltoft BL, Nordentoft M, Ostergaard SD, Eaton WW, Krogh J, Mortensen PB: Autoimmune diseases and severe infections as risk factors for mood disorders: a nationwide study. JAMA Psychiatry 2013;70:812-820.
52.
Matussek N: Neurobiologie und Depression. Med Monatsschr 1966;3:109-112.
53.
Coppen A, Swade C: 5-HT and depression: the present position; in Briley M, Fillion G (eds): New Concepts in Depression: Pierre Fabre Monograph Series. London, MacMillan Press, 1988, pp 120-136.
54.
Anisman H, Merali Z: Anhedonic and anxiogenic effects of cytokine exposure. Adv Exp Med Biol 1999;461:199-233.
55.
Day HE, Curran EJ, Watson SJ Jr, Akil H: Distinct neurochemical populations in the rat central nucleus of the amygdala and bed nucleus of the stria terminalis: evidence for their selective activation by interleukin-1β. J Comp Neurol 1999;413:113-128.
56.
Linthorst AC, Flachskamm C, Muller Preuss P, Holsboer F, Reul JM: Effect of bacterial endotoxin and interleukin-1β on hippocampal serotonergic neurotransmission, behavioral activity, and free corticosterone levels: an in vivo microdialysis study. J Neurosci 1995;15:2920-2934.
57.
Merali Z, Lacosta S, Anisman H: Effects of interleukin-1β and mild stress on alterations of norepinephrine, dopamine and serotonin neurotransmission: a regional microdialysis study. Brain Res 1997;761:225-235.
58.
Shintani F, Nakaki T, Kanba S, Sato K, Yagi G, Shiozawa M, Aiso S, Kato R, Asai M: Involvement of interleukin-1 in immobilization stress-induced increase in plasma adrenocorticotropic hormone and in release of hypothalamic monoamines in the rat. J Neurosci 1995;15:1961-1970.
59.
Song C, Merali Z, Anisman H: Variations of nucleus accumbens dopamine and serotonin following systemic interleukin-1, interleukin-2 or interleukin-6 treatment. Neuroscience 1999;88:823-836.
60.
Zalcman S, Green-Johnson JM, Murray L, Nance DM, Dyck D, Anisman H, Greenberg AH: Cytokine-specific central monoamine alterations induced by interleukin-1, -2 and -6. Brain Res 1994;643:40-49.
61.
Asnis GM, De La GR, Kohn SR, Reinus JF, Henderson M, Shah J: IFN-induced depression: a role for NSAIDs. Psychopharmacol Bull 2003;37:29-50.
62.
Raison CL, Capuron L, Miller AH: Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol 2006;27:24-31.
63.
Schäfer M, Horn M, Schmidt F, Schmid-Wendtner MH, Volkenandt M, Ackenheil M, Müller N, Schwarz MJ: Correlation between sICAM-1 and depressive symptoms during adjuvant treatment of melanoma with interferon-α. Brain Behav Immun 2004;18:555-562.
64.
Müller N, Schwarz MJ, Riedel M: COX-2 inhibition in schizophrenia: focus on clinical effects of celecoxib therapy and the role of TNF-α; in Eaton WW (ed): Medical and Psychiatric Comorbidity over the Course of Life. Washington, American Psychiatric Publishing, 2005, pp 265-276.
65.
Müller N, Schwarz MJ: The immune-mediated alteration of serotonin and glutamate: towards an integrated view of depression. Mol Psychiatry 2007;12:988-1000.
66.
Braun D, Longman RS, Albert ML: A two-step induction of indoleamine 2,3 dioxygenase (IDO) activity during dendritic-cell maturation. Blood 2005;106:2375-2381.
67.
Kwidzinski E, Bunse J, Aktas O, Richter D, Mutlu L, Zipp F, Nitsch R, Bechmann I: Indolamine 2,3-dioxygenase is expressed in the CNS and down-regulates autoimmune inflammation. FASEB J 2005;19:1347-1349.
68.
Robinson CM, Hale PT, Carlin JM: The role of IFN-γ and TNF-α-responsive regulatory elements in the synergistic induction of indoleamine dioxygenase. J Interferon Cytokine Res 2005;25:20-30.
69.
Kim JS, Schmid-Burgk W, Claus D, Kornhuber HH: Increased serum glutamate in depressed patients. Arch Psychiatr Nervenkr 1982;232:299-304.
70.
Altamura CA, Mauri MC, Ferrara A, Moro AR, D'Andrea G, Zamberlan F: Plasma and platelet excitatory amino acids in psychiatric disorders. Am J Psychiatry 1993;150:1731-1733.
71.
Mauri MC, Ferrara A, Boscati L, Bravin S, Zamberlan F, Alecci M, Invernizzi G: Plasma and platelet amino acid concentrations in patients affected by major depression and under fluvoxamine treatment. Neuropsychobiology 1998;37:124-129.
72.
Maes M, Verkerk R, Vandoolaeghe E, Lin A, Scharpe S: Serum levels of excitatory amino acids, serine, glycine, histidine, threonine, taurine, alanine and arginine in treatment-resistant depression: modulation by treatment with antidepressants and prediction of clinical responsivity. Acta Psychiatr Scand 1998;97:302-308.
73.
Kugaya A, Sanacora G: Beyond monoamines: glutamatergic function in mood disorders. CNS Spectr 2005;10:808-819.
74.
Sanacora G, Gueorguieva R, Epperson CN, Wu YT, Appel M, Rothman DL, Krystal JH, Mason GF: Subtype-specific alterations of γ-aminobutyric acid and glutamate in patients with major depression. Arch Gen Psychiatry 2004;61:705-713.
75.
Maj J, Rogoz Z, Skuza G, Sowinska H: Effects of MK-801 and antidepressant drugs in the forced swimming test in rats. Eur Neuropsychopharmacol 1992;2:37-41.
76.
Trullas R, Skolnick P: Functional antagonists at the NMDA receptor complex exhibit antidepressant actions. Eur J Pharmacol 1990;185:1-10.
77.
Yilmaz A, Schulz D, Aksoy A, Canbeyli R: Prolonged effect of an anesthetic dose of ketamine on behavioral despair. Pharmacol Biochem Behav 2002;71:341-344.
78.
Ossowska G, Klenk-Majewska B, Szymczyk G: The effect of NMDA antagonists on footshock-induced fighting behavior in chronically stressed rats. J Physiol Pharmacol 1997;48:127-135.
79.
Huber TJ, Dietrich DE, Emrich HM: Possible use of amantadine in depression. Pharmacopsychiatry 1999;32:47-55.
80.
Stryjer R, Strous RD, Shaked G, Bar F, Feldman B, Kotler M, Polak L, Rosenzcwaig S, Weizman A: Amantadine as augmentation therapy in the management of treatment-resistant depression. Int Clin Psychopharmacol 2003;18:93-96.
81.
Crane G: Cyloserine as an antidepressant agent. Am J Psychiatry 1959;115:1025-1026.
82.
Song C, Leonard BE: Fundamentals of psychoneuroimmunology. Chichester, J Wiley and Sons, 2000.
83.
Besedovsky H, del RA, Sorkin E, Da PM, Burri R, Honegger C: The immune response evokes changes in brain noradrenergic neurons. Science 1983;221:564-566.
84.
Schwarz MJ, Chiang S, Müller N, Ackenheil M: T-helper-1 and T-helper-2 responses in psychiatric disorders. Brain Behav Immun 2001;15:340-370.
85.
Myint AM, Kim YK: Cytokine-serotonin interaction through IDO: a neurodegeneration hypothesis of depression. Med Hypotheses 2003;61:519-525.
86.
Myint AM, Kim YK, Verkerk R, Scharpe S, Steinbusch H, Leonard B: Kynurenine pathway in major depression: evidence of impaired neuroprotection. J Affect Disord 2007;98:143-151.
87.
Frodl T, Meisenzahl EM, Zetzsche T, Born C, Groll C, Jager M, Leinsinger G, Bottlender R, Hahn K, Moller HJ: Hippocampal changes in patients with a first episode of major depression. Am J Psychiatry 2002;159:1112-1118.
88.
Frodl TS, Koutsouleris N, Bottlender R, Born C, Jager M, Scupin I, Reiser M, Moller HJ, Meisenzahl EM: Depression-related variation in brain morphology over 3 years: effects of stress? Arch Gen Psychiatry 2008;65:1156-1165.
89.
Cotter D, Pariante C, Rajkowska G: Glial pathology in major psychiatric disorders; in Agam G, Belmaker RH, Everall I (eds): The Post-Mortem Brain in Psychiatric Research. Boston, Kluwer Academic Pub, 2002, pp 291-324.
90.
Ongur D, Drevets WC, Price JL: Glial reduction in the subgenual prefrontal cortex in mood disorders. Proc Natl Acad Sci USA 1998;95:13290-13295.
91.
Rajkowska G, Miguel-Hidalgo JJ, Wei J, Dilley G, Pittman SD, Meltzer HY, Overholser JC, Roth BL, Stockmeier CA: Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression. Biol Psychiatry 1999;45:1085-1098.
92.
Rajkowska G, Halaris A, Selemon LD: Reductions in neuronal and glial density characterize the dorsolateral prefrontal cortex in bipolar disorder. Biol Psychiatry 2001;49:741-752.
93.
Rajkowska G: Depression: what we can learn from postmortem studies. Neuroscientist 2003;9:273-284.
94.
Johnston-Wilson NL, Sims CD, Hofmann J-P, Anderson L, Shore AD, Torrey EF, Yolken RH: Disease-specific alterations in frontal cortex brain proteins in schizophrenia, bipolar disorder, and major depressive disorder. Mol Psychiatry 2000;5:142-149.
95.
Miguel-Hidalgo JJ, Baucom C, Dilley G, Overholser JC, Meltzer HY, Stockmeier CA, Rajkowska G: Glial fibrillary acidic protein immunoreactivity in the prefrontal cortex distinguishes younger from older adults in major depressive disorder. Biol Psychiatry 2000;48:861-873.
96.
Si X, Miguel-Hidalgo JJ, O'Dwyer G, Stockmeier CA, Rajkowska G: Age-dependent reductions in the level of glial fibrillary acidic protein in the prefrontal cortex in major depression. Neuropsychopharmacology 2004;29:2088-2096.
97.
Davis S, Thomas A, Perry R, Oakley A, Kalaria RN, O'Brien JT: Glial fibrillary acidic protein in late life major depressive disorder: an immunocytochemical study. J Neurol Neurosurg Psychiatry 2002;73:556-560.
98.
Sandrini M, Vitale G, Pini LA: Effect of rofecoxib on nociception and the serotonin system in the rat brain. Inflamm Res 2002;51:154-159.
99.
Myint AM, Steinbusch HW, Goeghegan L, Luchtman D, Kim YK, Leonard BE: Effect of the COX-2 inhibitor celecoxib on behavioural and immune changes in an olfactory bulbectomised rat model of depression. Neuroimmunomodulation 2007;14:65-71.
100.
Brunello N, Alboni S, Capone G, Benatti C, Blom JM, Tascedda F, Kriwin P, Mendlewicz J: Acetylsalicylic acid accelerates the antidepressant effect of fluoxetine in the chronic escape deficit model of depression. Int Clin Psychopharmacol 2006;21:219-225.
101.
Müller N, Schwarz MJ, Dehning S, Douhet A, Cerovecki A, Goldstein-Müller B, Spellmann I, Hetzel G, Maino K, Kleindienst N, Möller HJ, Arolt V, Riedel M: The cyclooxygenase-2 inhibitor celecoxib has therapeutic effects in major depression: results of a double-blind, randomized, placebo controlled, add-on pilot study to reboxetine. Mol Psychiatry 2006;11:680-684.
102.
Akhondzadeh S, Jafari S, Raisi F, Ghoreishi A, Salehi B, Mohebbi-Rasa S, Raznahan M, Kamalipour A: Clinical trial of adjunctive celecoxib treatment in patients with major depression: a double blind and placebo controlled trial. Depress Anxiety:2009;26:607-611.
103.
Abbasi SH, Hosseini F, Modabbernia A, Ashrafi M, Akhondzadeh S: Effect of celecoxib add-on treatment on symptoms and serum IL-6 concentrations in patients with major depressive disorder: randomized double-blind placebo-controlled study. J Affect Disord 2012;141:308-314.
104.
Tyring S, Gottlieb A, Papp K, Gordon K, Leonardi C, Wang A, Lalla D, Woolley M, Jahreis A, Zitnik R, Cella D, Krishnan R: Etanercept and clinical outcomes, fatigue, and depression in psoriasis: double-blind placebo-controlled randomised phase III trial. Lancet 2006;367:29-35.
105.
Raison CL, Rutherford RE, Woolwine BJ, Shuo C, Schettler P, Drake DF, Haroon E, Miller AH: A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry 2013;70:31-41.
106.
Benicky J, Sanchez-Lemus E, Honda M, Pang T, Orecna M, Wang J, Leng Y, Chuang DM, Saavedra JM: Angiotensin II AT1 receptor blockade ameliorates brain inflammation. Neuropsychopharmacology 2011;36:857-870.
107.
Saavedra JM, Sanchez-Lemus E, Benicky J: Blockade of brain angiotensin II AT1 receptors ameliorates stress, anxiety, brain inflammation and ischemia: therapeutic implications. Psychoneuroendocrinology 2011;36:1-18.
108.
Craddock N, Owen MJ: The Kraepelinian dichotomy - going, going... but still not gone. Br J Psychiatry 2010;196:92-95.
109.
Müller N: Immunology of schizophrenia. Neuroimmunomodulation 2014;21:109-116.
110.
Dutt A, Ganguly T, Shaikh M, Walshe M, Schulze K, Marshall N, Constante M, McDonald C, Murray RM, Allin MP, Bramon E: Association between hippocampal volume and P300 event related potential in psychosis: support for the Kraepelinian divide. Neuroimage 2012;59:997-1003.
111.
Radonic E, Rados M, Kalember P, Bajs-Janovic M, Folnegovic-Smalc V, Henigsberg N: Comparison of hippocampal volumes in schizophrenia, schizoaffective and bipolar disorder. Coll Antropol 2011;35(suppl 1):249-252.
112.
Savitz JB, Nugent AC, Bogers W, Roiser JP, Bain EE, Neumeister A, Zarate CA Jr, Manji HK, Cannon DM, Marrett S, Henn F, Charney DS, Drevets WC: Habenula volume in bipolar disorder and major depressive disorder: a high-resolution magnetic resonance imaging study. Biol Psychiatry 2011;69:336-343.
113.
Winter C, Vollmayr B, Djodari-Irani A, Klein J, Sartorius A: Pharmacological inhibition of the lateral habenula improves depressive-like behavior in an animal model of treatment resistant depression. Behav Brain Res 2011;216:463-465.
114.
Müller N, Schwarz MJ: A psychoneuroimmunological perspective to Emil Kraepelins dichotomy: schizophrenia and major depression as inflammatory CNS disorders. Eur Arch Psychiatry Clin Neurosci 2008;258(suppl 2):97-106.
115.
Müller N: Infectious diseases and mental health; in Sartorius N, Maj M, Holt R (eds): Comorbidity of Mental and Physical Disorders. Key Issues Ment Health. Basel, Karger, 2014, vol 180 (in press).
116.
Müller N, Bechter K: The mild encephalitis concept for psychiatric disorders revisited in the light of current psychoneuroimmunological findings. Neurology, Psychiatry and Brain Research 2013;19:87-101.
© 2014 S. Karger AG, Basel
2014
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.
