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Inflammation and depression: a causal or coincidental link to the pathophysiology?

  • Brian E. Leonard (a1)
Abstract

This review summarises the evidence that chronic low grade inflammation triggers changes that contribute to the mental and physical ill health of patients with major depression. Inflammation, and the activation of the hypothalamic pituitary axis by stress, are normal components of the stress response but when stress is prolonged and the endocrine and immune system become chronic resulting in the activation of the peripheral macrophages, the central microglia and hypercortisolemia, the neuronal networks are damaged and become dysfunctional. The proinflammatory cytokines, in addition to activating the hypothalamic–pituitary–adrenal axis and thereby increasing cortisol synthesis, also activate the tryptophan–kynurenine pathway. This results in the synthesis of the neurotoxic N-methyl-d-aspartate (NMDA) glutamate agonist quinolinic acid and 3-hydroxykynurenine thereby enhancing oxidative stress and contributes to neurodegeneration which characterise major depression particularly in late life.While antidepressants attenuate some of the endocrine and immune changes caused by inflammation, not all therapeutically effective antidepressants do so. This suggests that drugs which specifically target the immune, endocrine and neurotransmitter systems may be more effective antidepressants.The preliminary clinical evidence that some non-steroidal anti-inflammatory drugs, such as the cyclooxygenase 2 inhibitor celecoxib, can enhance the response to standard antidepressant treatment is therefore considered and a critical assessment made of the possible limitations of such an approach to novel antidepressant development.

Copyright
Corresponding author
Brian E. Leonard, Emeritus Professor of Pharmacology, National University of Ireland, University Road, Galway. Tel: +353-91-555292; Fax: +353-91-25700; E-mail: psycholeonard@gmail.com
References
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1. Quan, N, Banks, WA. Brain-immune communication pathways. Brain Behav Immun 2007;21:727735.
2. Lee, YJ, Han, SB, Nam, SY, Oh, KW, Hong, JT. Inflammation and Alzheimer’s disease. Arch Pharm Res 2010;33:15391556.
3. Abbas, AK, Lichtman, AH, Pillai, S. Cellular and molecular immunology. Philadelphia, PA: Elsevier Saunders, 2015.
4. Hickey, WF. Basic principles of immunological surveillance of the normal central nervous system. Glia 2001;36:118124.
5. Ermisch, A, Ruhle, HJ, Landgraf, R, Hess, J. Blood-brain barrier and peptides. J Cereb Blood Flow Metab 1985;5:350357.
6. Greenwood, J, Wang, Y, Calder, VL. Lymphocyte adhesion and transendothelial migration in the central nervous system: the role of LFA-1, ICAM-1, VLA-4 and VCAM-1. off. Immunology 1995;86:408415.
7. Ferrari, D, Pizzirani, C, Adinolfi, E et al. The P2×7 receptor: a key player in IL-1 processing and release. Journal of Immunol 2006;176(7):38773883.
8. Iwata, M, Ota, KT, Duman, RS. The inflammasome: pathways linking psychological stress, depression, and systemic illnesses. Brain Behav Immun 2013;31:105114.
9. Nimmerjahn, A, Kirchhoff, F, Helmchen, F. Resting microglial cells are highly dynamic surveillants of brain parenchyma in vivo. Science 2005;308:13141318.
10. Prinz, M, Priller, J. Tickets to the brain: role of CCR2 and CX3CR1 in myeloid cell entry in the CNS. J Neuroimmunol 2010;224:8084.
11. Godbout, JP, Moreau, M, Lestage, J et al. Aging exacerbates depressive-like behavior in mice in response to activation of the peripheral innate immune system. Neuropsychopharmacology 2008;33:23412351.
12. Wynne, AM, Henry, CJ, Huang, Y, Cleland, A, Godbout, JP. Protracted downregulation of CX3CR1 on microglia of aged mice after lipopolysaccharide challenge. Brain Behav Immun 2010;24:11901201.
13. Leonard, BE. Inflammation, depression and dementia: are they connected? Neurochem Res 2007;32:17491756.
14. Galic, MA, Riazi, K, Pittman, QJ. Cytokines and brain excitability. Front Neuroendocrinol 2012;33:116125.
15. Rothermundt, M, Falkai, P, Ponath, G et al. Glial cell dysfunction in schizophrenia indicated by increased S100B in the CSF. Mol Psychiatry 2004;9:897899.
16. Parker, LC, Luheshi, GN, Rothwell, NJ, Pinteaux, E. IL-1 beta signalling in glial cells in wildtype and IL-1RI deficient mice. Br J Pharmacol 2002;136:312320.
17. Ericsson, A, Arias, C, Sawchenko, PE. Evidence for an intramedullary prostaglandin-dependent mechanism in the activation of stress-related neuroendocrine circuitry by intravenous interleukin-1. J Neurosci 1997;17:71667179.
18. Paakkari, I, Lindsberg, P. Nitric oxide in the central nervous system. Ann Med 1995;27:369377.
19. Pariante, CM, Miller, AH. Glucocorticoid receptors in major depression: relevance to pathophysiology and treatment. Biol Psychiatry 2001;49:391404.
20. Juruena, MF, Cleare, AJ, Papadopoulos, AS, Poon, L, Lightman, S, Pariante, CM. Different responses to dexamethasone and prednisolone in the same depressed patients. Psychopharmacology 2006;189:225235.
21. Pollak, Y, Yirmiya, R. Cytokine-induced changes in mood and behaviour: implications for ‘depression due to a general medical condition’, immunotherapy and antidepressive treatment. Int J Neuropsychopharmacol 2002;5:389399.
22. Raison, CL, Capuron, L, Miller, AH. Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol 2006;27:2431.
23. Segerstrom, SC, Miller, GE. Psychological stress and the human immune system: a meta-analytic study of 30 years of inquiry. Psychol Bull 2004;130:601630.
24. Quan, N, Avitsur, R, Stark, JL et al. Molecular mechanisms of glucocorticoid resistance in splenocytes of socially stressed male mice. J Neuroimmunol 2003;137:5158.
25. Pace, TW, Miller, AH. Cytokines and glucocorticoid receptor signaling. Relevance to major depression. Ann NY Acad Sci 2009;1179:86105.
26. Lucassen, PJ, Meerlo, P, Naylor, AS et al. Regulation of adult neurogenesis by stress, sleep disruption, exercise and inflammation: implications for depression and antidepressant action. Eur Neuropsychopharmacol 2010;20:117.
27. Zunszain, PA, Anacker, C, Cattaneo, A et al. Interleukin-1beta: a new regulator of the kynurenine pathway affecting human hippocampal neurogenesis. Neuropsychopharmacology 2012;37:939949.
28. Goshen, I, Kreisel, T, Ben-Menachem-Zidon, O et al. Brain interleukin-1 mediates chronic stress-induced depression in mice via adrenocortical activation and hippocampal neurogenesis suppression. Mol Psychiatry 2008;13:717728.
29. Stefanski, V. Social stress in laboratory rats: hormonal responses and immune cell distribution. Psychoneuroendocrinology 2000;25:389406.
30. Quan, N, Avitsur, R, Stark, JL et al. Social stress increases the susceptibility to endotoxic shock. J Neuroimmunol 2001;115:3645.
31. Quan, N, He, L, Lai, W, Shen, T, Herkenham, M. Induction of IkappaBalpha mRNA expression in the brain by glucocorticoids: a negative feedback mechanism for immune-to-brain signaling. J Neurosci 2000;20:64736477.
32. De Kloet, ER, Vreugdenhil, E, Oitzl, MS, Joels, M. Brain corticosteroid receptor balance in health and disease. Endocr Rev 1998;19:269301.
33. Sugama, S, Fujita, M, Hashimoto, M, Conti, B. Stress induced morphological microglial activation in the rodent brain: involvement of interleukin-18. Neuroscience 2007;146:13881399.
34. Steiner, J, Bielau, H, Brisch, R et al. Immunological aspects in the neurobiology of suicide: elevated microglial density in schizophrenia and depression is associated with suicide. J Psychiatr Res 2008;42:151157.
35. Glaser, R, Robles, TF, Sheridan, J, Malarkey, WB, Kiecolt-Glaser, JK. Mild depressive symptoms are associated with amplified and prolonged inflammatory responses after influenza virus vaccination in older adults. Arch Gen Psychiatry 2003;60:10091014.
36. Ongur, D, Drevets, WC, Price, JL. Glial reduction in the subgenual prefrontal cortex in mood disorders. Proc Natl Acad Sci USA 1998;95:1329013295.
37. Myint, AM. Inflammation, neurotoxins and psychiatric disorders. Mod Trends Pharmacopsychiatri 2013;28:6174.
38. Duman, RS, Heninger, GR, Nestler, EJ. A molecular and cellular theory of depression. Arch Gen Psychiatry 1997;54:597606.
39. Yeager, MP, Pioli, PA, Guyre, PM. Cortisol exerts bi-phasic regulation of inflammation in humans. Dose Response 2011;9:332347.
40. Smyth, GP, Stapleton, PP, Freeman, TA et al. Glucocorticoid pretreatment induces cytokine overexpression and nuclear factor-kappaB activation in macrophages. J Surg Res 2004;116:253261.
41. Maes, M, Bosmans, E, De Jongh, R, Kenis, G, Vandoolaeghe, E, Neels, H. Increased serum IL-6 and IL-1 receptor antagonist concentrations in major depression and treatment resistant depression. Cytokine 1997;9:853858.
42. Maes, M, Yirmyia, R, Noraberg, J et al. The inflammatory & neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression. Metab Brain Dis 2009;24:2753.
43. Sheline, YI, Mittler, BL, Mintun, MA. The hippocampus and depression. Eur Psychiatry 2002;17(Suppl. 3):300305.
44. Myint, AM, Kim, YK. Cytokine-serotonin interaction through IDO: a neurodegeneration hypothesis of depression. Med Hypotheses 2003;61:519525.
45. Kent, S, Bluthe, RM, Kelley, KW, Dantzer, R. Sickness behavior as a new target for drug development. Trends Pharmacol Sci 1992;13:2428.
46. Hart, BL. Biological basis of the behavior of sick animals. Neurosci Biobehav Rev 1988;12:123137.
47. Raison, CL, Miller, AH. Malaise, melancholia and madness: the evolutionary legacy of an inflammatory bias. Brain Behav Immun 2013;31:18.
48. Janicki-Deverts, D, Cohen, S, Doyle, WJ, Turner, RB, Treanor, JJ. Infection-induced proinflammatory cytokines are associated with decreases in positive affect, but not increases in negative affect. Brain Behav Immun 2007;21:301307.
49. Yirmiya, R, Pollak, Y, Barak, O et al. Effects of antidepressant drugs on the behavioral and physiological responses to lipopolysaccharide (LPS) in rodents. Neuropsychopharmacology 2001;24:531544.
50. Kenis, G, Maes, M. Effects of antidepressants on the production of cytokines. Int J Neuropsychopharmacol 2002;5:401412.
51. Yaron, I, Shirazi, I, Judovich, R, Levartovsky, D, Caspi, D, Yaron, M. Fluoxetine and amitriptyline inhibit nitric oxide, prostaglandin E2, and hyaluronic acid production in human synovial cells and synovial tissue cultures. Arthritis Rheum 1999;42:25612568.
52. Song, C, Leonard, BE. The olfactory bulbectomised rat as a model of depression. Neurosci Biobehav Rev 2005;29:627647.
53. Myint, AM, O’Mahony, S, Kubera, M et al. Role of paroxetine in interferon-alpha-induced immune and behavioural changes in male Wistar rats. J Psychopharmacol 2007;21:843850.
54. Jazayeri, S, Keshavarz, SA, Tehrani-Doost, M et al. Effects of eicosapentaenoic acid and fluoxetine on plasma cortisol, serum interleukin-1beta and interleukin-6 concentrations in patients with major depressive disorder. Psychiatry Res 2010;178:112115.
55. Maes, M, Meltzer, HY, Bosmans, E et al. Increased plasma concentrations of interleukin-6, soluble interleukin-6, soluble interleukin-2 and transferrin receptor in major depression. J Affect Disord 1995;34:301309.
56. Lee, HJ, Rao, JS, Ertley, RN, Chang, L, Rapoport, SI, Bazinet, RP. Chronic fluoxetine increases cytosolic phospholipase A(2) activity and arachidonic acid turnover in brain phospholipids of the unanesthetized rat. Psychopharmacology 2007;190:103115.
57. Geerlings, MI, den Heijer, T, Koudstaal, PJ, Hofman, A, Breteler, MM. History of depression, depressive symptoms, and medial temporal lobe atrophy and the risk of Alzheimer disease. Neurology 2008;70:12581264.
58. Jorm, AF. History of depression as a risk factor for dementia: an updated review. Aust NZ J Psychiatry 2001;35:776781.
59. Rapp, MA, Schnaider-Beeri, M, Grossman, HT et al. Increased hippocampal plaques and tangles in patients with Alzheimer disease with a lifetime history of major depression. Arch Gen Psychiatry 2006;63:161167.
60. Sun, X, Steffens, DC, Au, R et al. Amyloid-associated depression: a prodromal depression of Alzheimer disease? Arch Gen Psychiatry 2008;65:542550.
61. Leonard, BE. Changes in the immune system in depression and dementia: causal or co-incidental effects? Int J Dev Neurosci 2001;19:305312.
62. Leonard, BE, Myint, A. Changes in the immune system in depression and dementia: causal or coincidental effects? Dialogues Clin Neurosci 2006;8:163174.
63. Lapin, IP, Oxenkrug, GF. Intensification of the central serotoninergic processes as a possible determinant of the thymoleptic effect. Lancet 1969;1:132136.
64. Lapin, IP. Kynurenines as probable participants of depression. Pharmakopsychiatr Neuro-Psychopharmakol 1973;6:273279.
65. Satyanarayana, U, Rao, BS. Dietary tryptophan level and the enzymes of tryptophan NAD pathway. Br J Nutr 1980;43:107113.
66. Carlin, JM, Borden, EC, Sondel, PM, Byrne, GI. Interferon-induced indoleamine 2,3-dioxygenase activity in human mononuclear phagocytes. J Leukoc Biol 1989;45:2934.
67. Taylor, MW, Feng, GS. Relationship between interferon-gamma, indoleamine 2,3-dioxygenase, and tryptophan catabolism. FASEB J 1991;5:25162522.
68. Gal, EM, Sherman, AD. L-kynurenine: its synthesis and possible regulatory function in brain. Neurochem Res 1980;5:223239.
69. Perkins, MN, Stone, TW. An iontophoretic investigation of the actions of convulsant kynurenines and their interaction with the endogenous excitant quinolinic acid. Brain Res 1982;247:184187.
70. Grant, RS, Kapoor, V. Murine glial cells regenerate NAD, after peroxide-induced depletion, using either nicotinic acid, nicotinamide, or quinolinic acid as substrates. J Neurochem 1998;70:17591763.
71. Guillemin, GJ, Smythe, G, Takikawa, O, Brew, BJ. Expression of indoleamine 2,3-dioxygenase and production of quinolinic acid by human microglia, astrocytes, and neurons. Glia 2005;49:1523.
72. Guillemin, GJ, Smith, DG, Kerr, SJ et al. Characterisation of kynurenine pathway metabolism in human astrocytes and implications in neuropathogenesis. Redox Rep 2000;5:108111.
73. Guillemin, GJ, Wang, L, Brew, BJ. Quinolinic acid selectively induces apoptosis of human astrocytes: potential role in AIDS dementia complex. J Neuroinflammation 2005;2:16.
74. Bremner, JD, Narayan, M, Anderson, ER, Staib, LH, Miller, HL, Charney, DS. Hippocampal volume reduction in major depression. Am J Psychiatry 2000;157:115118.
75. van Erp, TG, Saleh, PA, Huttunen, M et al. Hippocampal volumes in schizophrenic twins. Arch Gen Psychiatry 2004;61:346353.
76. Steiner, J, Walter, M, Gos, T et al. Severe depression is associated with increased microglial quinolinic acid in subregions of the anterior cingulate gyrus: evidence for an immune-modulated glutamatergic neurotransmission? J Neuroinflammation 2011;8:94.
77. Myint, AM, Schwarz, MJ, Muller, N. The role of the kynurenine metabolism in major depression. J Neural Transm 2012;119:245251.
78. Han, Q, Cai, T, Tagle, DA, Li, J. Structure, expression, and function of kynurenine aminotransferases in human and rodent brains. Cell Mol Life Sci 2010;67:353368.
79. Oxenkrug, G. Insulin resistance and dysregulation of tryptophan-kynurenine and kynurenine-nicotinamide adenine dinucleotide metabolic pathways. Mol Neurobiol 2013;48:294301.
80. Lee, S, Tong, M, Hang, S, Deochand, C, de la Monte, S. CSF and brain indices of insulin resistance, oxidative stress and neuro-inflammation in early versus late Alzheimer’s disease. J Alzheimers Dis Parkinsonism 2013;3:128.
81. Sas, K, Robotka, H, Toldi, J, Vecsei, L. Mitochondria, metabolic disturbances, oxidative stress and the kynurenine system, with focus on neurodegenerative disorders. J Neurol Sci 2007;257:221239.
82. Maes, M, Meltzer, HY. The serotonin hypothesis of major depression. In: Bloom FE, editor. Psychopharmacology the 3rd generation of progress. NY: Raven Press, 1995; p. 946993.
83. Nutt, DJ. The neuropharmacology of serotonin and noradrenaline in depression. International Clinical Psychopharmacology 2002;17(Suppl. 1):S1S12.
84. Tang, SW, Helmeste, DM, Leonard, B. Antidepressant compounds: a critical review. Mod Trends Pharmacopsychiatry 2010;27:119.
85. Wong, ML, Kling, MA, Munson, PJ et al. Pronounced and sustained central hypernoradrenergic function in major depression with melancholic features: relation to hypercortisolism and corticotropin-releasing hormone. Proc Natl Acad Sci USA 2000;97:325330.
86. Manji, HK, Drevets, WC, Charney, DS. The cellular neurobiology of depression. Nat Med 2001;7:541547.
87. Malberg, JE, Blendy, JA. Antidepressant action: to the nucleus and beyond. Trends Pharmacol Sci 2005;26:631638.
88. Wong, ML, Whelan, F, Deloukas, P et al. Phosphodiesterase genes are associated with susceptibility to major depression and antidepressant treatment response. Proc Natl Acad Sci USA 2006;103:1512415129.
89. Castanon, N, Leonard, BE, Neveu, PJ, Yirmiya, R. Effects of antidepressants on cytokine production and actions. Brain Behav Immun 2002;16:569574.
90. Maes, M, Song, C, Lin, AH et al. Negative immunoregulatory effects of antidepressants: inhibition of interferon-gamma and stimulation of interleukin-10 secretion. Neuropsychopharmacology 1999;20:370379.
91. Xia, Z, DePierre, JW, Nassberger, L. 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 1996;34:2737.
92. Hashioka, S, Klegeris, A, Monji, A et al. Antidepressants inhibit interferon-gamma-induced microglial production of IL-6 and nitric oxide. Exp Neurol 2007;206:3342.
93. Baumann, P, Hiemke, C, Ulrich, S et al. Therapeutic monitoring of psychotropic drugs: an outline of the AGNP-TDM expert group consensus guideline. Ther Drug Monit 2004;26:167170.
94. Anisman, H, Merali, Z, Hayley, S. Neurotransmitter, peptide and cytokine processes in relation to depressive disorder: comorbidity between depression and neurodegenerative disorders. Prog Neurobiol 2008;85:174.
95. Harkin, AJ, Bruce, KH, Craft, B, Paul, IA. Nitric oxide synthase inhibitors have antidepressant-like properties in mice. 1. Acute treatments are active in the forced swim test. Eur J Pharmacol 1999;372:207213.
96. Manji, HK, Quiroz, JA, Sporn, J et al. Enhancing neuronal plasticity and cellular resilience to develop novel, improved therapeutics for difficult-to-treat depression. Biol Psychiatry 2003;53:707742.
97. Wegener, G, Mathé, AA. Nitric oxide signaling in depression and antidepressant action. In: Lopez-Munoz F, Alamo C, editors. Neurobiology of depression. Frontiers in neuroscience. Boca Raton: CRC Press, 2012; p. 341370.
98. Wegener, G, Volke, V. Nitric oxide synthase inhibitors as antidepressants. Pharmaceuticals 2010;3:273299.
99. Muller, N. 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;11:680684.
100. Ekdahl, CT, Claasen, JH, Bonde, S, Kokaia, Z, Lindvall, O. Inflammation is detrimental for neurogenesis in adult brain. Proc Natl Acad Sci USA 2003;100:1363213637.
101. Joca, SR, Guimaraes, FS. Inhibition of neuronal nitric oxide synthase in the rat hippocampus induces antidepressant-like effects. Psychopharmacology 2006;185:298305.
102. Heiberg, IL, Wegener, G, Rosenberg, R. Reduction of cGMP and nitric oxide has antidepressant-like effects in the forced swimming test in rats. Behav Brain Res 2002;134:479484.
103. Volke, V, Wegener, G, Bourin, M, Vasar, E. Antidepressant- and anxiolytic-like effects of selective neuronal NOS inhibitor 1-(2-trifluoromethylphenyl)-imidazole in mice. Behav Brain Res 2003;140:141147.
104. Harkin, A, Connor, TJ, Walsh, M, St John, N, Kelly, JP. Serotonergic mediation of the antidepressant-like effects of nitric oxide synthase inhibitors. Neuropharmacology 2003;44:616623.
105. Horikawa, H, Kato, TA, Mizoguchi, Y et al. Inhibitory effects of SSRIs on IFN-gamma induced microglial activation through the regulation of intracellular calcium. Prog Neuropsychopharmacol Biol Psychiatry 2010;34:13061316.
106. O’Sullivan, JB, Ryan, KM, Curtin, NM, Harkin, A, Connor, TJ. Noradrenaline reuptake inhibitors limit neuroinflammation in rat cortex following a systemic inflammatory challenge: implications for depression and neurodegeneration. Int J Neuropsychopharmacol 2009;12:687699.
107. Weber, J, Lyseng-Williamson, KA, Scott, LJ. Aripiprazole: in major depressive disorder. CNS Drugs 2008;22:807813.
108. Kato, T, Mizoguchi, Y, Monji, A et al. Inhibitory effects of aripiprazole on interferon-gamma-induced microglial activation via intracellular Ca2+ regulation in vitro. J Neurochem 2008;106:815825.
109. Honda, T, Segi-Nishida, E, Miyachi, Y, Narumiya, S. Prostacyclin-IP signaling and prostaglandin E2-EP2/EP4 signaling both mediate joint inflammation in mouse collagen-induced arthritis. J Exp Med 2006;203:325335.
110. Narumiya, S. Prostanoids and inflammation: a new concept arising from receptor knockout mice. J Mol Med 2009;87:10151022.
111. Aoki, T, Narumiya, S. Prostaglandins and chronic inflammation. Trends Pharmacol Sci 2012;33:304311.
112. van Gijn, J, Kerr, RS, Rinkel, GJ. Subarachnoid haemorrhage. Lancet 2007;369:306318.
113. Phillis, JW, Horrocks, LA, Farooqui, AA. Cyclooxygenases, lipoxygenases, and epoxygenases in CNS: their role and involvement in neurological disorders. Brain Res Rev 2006;52:201243.
114. Niwa, K, Araki, E, Morham, SG, Ross, ME, Iadecola, C. Cyclooxygenase-2 contributes to functional hyperemia in whisker-barrel cortex. J Neurosci 2000;20:763770.
115. Zhang, Y, Desai, A, Yang, SY et al. TISSUE REGENERATION. Inhibition of the prostaglandin-degrading enzyme 15-PGDH potentiates tissue regeneration. Science 2015;348:aaa2340.
116. Bertolini, A, Ottani, A, Sandrini, M. Selective COX-2 inhibitors and dual acting anti-inflammatory drugs: critical remarks. Curr Med Chem 2002;9:10331043.
117. Pepicelli, O, Fedele, E, Berardi, M et al. Cyclo-oxygenase-1 and -2 differently contribute to prostaglandin E2 synthesis and lipid peroxidation after in vivo activation of N-methyl-D-aspartate receptors in rat hippocampus. J Neurochem 2005;93:15611567.
118. Blais, V, Turrin, NP, Rivest, S. Cyclooxygenase 2 (COX-2) inhibition increases the inflammatory response in the brain during systemic immune stimuli. J Neurochem 2005;95:15631574.
119. Muller, N. COX-2 inhibitors as antidepressants and antipsychotics: clinical evidence. Curr Opin Investig Drugs 2010;11:3142.
120. Mattsson, N, Yaong, M, Rosengren, L et al. Elevated cerebrospinal fluid levels of prostaglandin E2 and 15-(S)-hydroxyeicosatetraenoic acid in multiple sclerosis. J Intern Med 2009;265:459464.
121. Ahmad, M, Rose, ME, Vagni, V et al. Genetic disruption of cyclooxygenase-2 does not improve histological or behavioral outcome after traumatic brain injury in mice. J Neurosci Res 2008;86:36053612.
122. Mendlewicz, J, Kriwin, P, Oswald, P, Souery, D, Alboni, S, Brunello, N. Shortened onset of action of antidepressants in major depression using acetylsalicylic acid augmentation: a pilot open-label study. Int Clin Psychopharmacol 2006;21:227231.
123. Serhan, CN, Chiang, N. Endogenous pro-resolving and anti-inflammatory lipid mediators: a new pharmacologic genus. Br J Pharmacol 2008;153(Suppl. 1):S200S215.
124. Kozak, KR, Crews, BC, Morrow, JD et al. Metabolism of the endocannabinoids, 2-arachidonylglycerol and anandamide, into prostaglandin, thromboxane, and prostacyclin glycerol esters and ethanolamides. J Biol Chem 2002;277:4487744885.
125. Wolf, SA, Ullrich, O. Endocannabinoids and the brain immune system: new neurones at the horizon? J Neuroendocrinol 2008;20(Suppl. 1):1519.
126. Jiang, J, Dingledine, R. Prostaglandin receptor EP2 in the crosshairs of anti-inflammation, anti-cancer, and neuroprotection. Trends Pharmacol Sci 2013;34:413423.
127. Johansson, D, Falk, A, Marcus, MM, Svensson, TH. Celecoxib enhances the effect of reboxetine and fluoxetine on cortical noradrenaline and serotonin output in the rat. Prog Neuropsychopharmacol Biol Psychiatry 2012;39:143148.
128. Molina-Hernandez, M, Tellez-Alcantara, NP, Perez-Garcia, J, Olivera-Lopez, JI, Jaramillo-Jaimes, MT. Antidepressant-like actions of minocycline combined with several glutamate antagonists. Prog Neuropsychopharmacol Biol Psychiatry 2008;32:380386.
129. Levine, J, Cholestoy, A, Zimmerman, J. Possible antidepressant effect of minocycline. Am J Psychiatry 1996;153:582.
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