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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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