New drug targets in depression: Inflammatory, cell-mediate immune, oxidative and nitrosative stress, mitochondrial, antioxidant, and neuroprogressive pathways. and new drug candidates-Nrf2 activators and GSK-3 inhibitors

Inflammopharmacology

Volumn 20, Issue 3, 2012, Pages 127-150

  Maes, Michael ^a   Fišar, Zdeněk ^b   Medina, Miguel ^c   Scapagnini, Giovanni ^d   Nowak, Gabriel ^e   Berk, Michael ^f,g,h  

^a Maes Clinics at TRIA   (Thailand)

^b CHARLES UNIVERSITY   (Czech Republic)

^c Noscira   (Spain)

^d UNIVERSITY OF MOLISE   (Italy)

^e JAGIELLONIAN UNIVERSITY MEDICAL COLLEGE   (Poland)

^f UNIVERSITY OF MELBOURNE   (Australia)

^g UNIVERSITY OF MELBOURNE   (Australia)

^h FLOREY INSTITUTE OF NEUROSCIENCE AND MENTAL HEALTH   (Australia)

Author keywords

Antidepressants; Cytokines; Depression; Inflammation; Neuroprogression; Oxidative and nitrosative stress; Serotonin

Indexed keywords

ACETYLCYSTEINE; ACETYLSALICYLIC ACID; AGOMELATINE; ANTIDEPRESSANT AGENT; CELECOXIB; CURCUMIN; CYCLOOXYGENASE 2 INHIBITOR; CYTOKINE RECEPTOR ANTAGONIST; ETANERCEPT; FENFLURAMINE; GLYCOGEN SYNTHASE KINASE 3 INHIBITOR; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; IMIPRAMINE; KETAMINE; LIQUIRITIN; LITHIUM; LOSMAPIMOD; MINOCYCLINE; NONSTEROID ANTIINFLAMMATORY AGENT; OMEGA 3 FATTY ACID; PLACEBO; RESVERATROL; SAPONIN; SEROTONIN UPTAKE INHIBITOR; SERTRALINE; TRANSCRIPTION FACTOR NRF2; UBIDECARENONE; UNINDEXED DRUG; VALPROIC ACID; ZINC;

ANTIDEPRESSANT ACTIVITY; ANTIINFLAMMATORY ACTIVITY; ANTIOXIDANT ACTIVITY; APOPTOSIS; BIPOLAR DISORDER; CELLULAR IMMUNITY; COMBINATION CHEMOTHERAPY; CYTOKINE PRODUCTION; DEPRESSION; DISORDERS OF MITOCHONDRIAL FUNCTIONS; DNA DAMAGE; DRUG DESIGN; DRUG EFFICACY; DRUG POTENTIATION; DRUG TARGETING; ELECTROCONVULSIVE THERAPY; ENZYME ACTIVITY; HUMAN; LIPID PEROXIDATION; NERVE CELL PLASTICITY; NERVE DEGENERATION; NERVOUS SYSTEM INFLAMMATION; NEUROPATHOLOGY; NEUROPROTECTION; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; REVIEW;

ANIMALS; ANTIOXIDANTS; DEPRESSION; DISEASE PROGRESSION; DRUG DELIVERY SYSTEMS; GLYCOGEN SYNTHASE KINASE 3; HUMANS; IMMUNITY, CELLULAR; INFLAMMATION MEDIATORS; MITOCHONDRIA; NF-E2-RELATED FACTOR 2; NITROSATION; OXIDATIVE STRESS;

EID: 84862769027     PISSN: 09254692     EISSN: 15685608     Source Type: Journal    
DOI: 10.1007/s10787-011-0111-7     Document Type: Review

References (297)

1. Abdel-Razaq W, Kendall DA, Bates TE (2011) The effects of antidepressants on mitochondrial function in a model cell system and isolated mitochondria. Neurochem Res 36(2):327-338
2. Albrecht P, Lewerenz J, Dittmer S, Noack R, Maher P, Methner A (2010) Mechanisms of oxidative glutamate toxicity: the gluta-mate/cystine antiporter system xc-as a neuroprotective drug target. CNS Neurol Disord Drug Targets 9:373-382
3. Ames BN (2003) Delaying the mitochondrial decay of aging-a metabolic tune-up. Alzheimer Dis Assoc Disord 17(Suppl 2): S54-S57
4. Amminger GP, Schäfer MR, Klier CM, Slavik J-M, Holzer I, Holub M, Goldstone S, Whitford TJ, Berk M (2011) Decreased nervonic acid levels in erythrocyte membranes predict psychosis in help-seeking ultra-high risk individuals. Mol Psychiatry (in press)
5. Anisman H, Merali Z (1999) Anhedonic and anxiogenic effects of cytokine exposure. Adv Exp Med Biol 461:199-233
6. Anttila S, Huuhka K, Huuhka M, Rontu R, Hurme M, Leinonen E, Lehtimaki T (2007) Interaction between 5-HT1A and BDNF genotypes increases the risk of treatment-resistant depression. J Neural Transm 114(8):1065-1068
7. Arakawa H, Blandino P Jr, Deak T (2009) Central infusion of interleukin-1 receptor antagonist blocks the reduction in social behavior produced by prior stressor exposure. Physiol Behav 98(1-2):139-146
8. Atlante A, Calissano P, Bobba A, Giannattasio S, Marra E, Passarella S (2001) Glutamate neurotoxicity, oxidative stress and mitochondria. FEBS Lett 497(1):1-5
9. Bachmann RF, Wang Y, Yuan P, Zhou R, Li X, Alesci S, Du J, Manji HK (2009) Common effects of lithium and valproate on mitochondrial functions: protection against methamphetamine-induced mitochondrial damage. Int J Neuropsychopharmacol 12(6):805-822
10. Baker DA, Xi ZX, Shen H et al (2002) The origin and neuronal function of in vivo nonsynaptic glutamate. J Neurosci 22:9134-9141
11. Baker DA, McFarland K, Lake RW, Shen H, Tang XC, Toda S, Kalivas PW (2003) Neuroadaptations in cystine-glutamate exchange underlie cocaine relapse. Nat Neurosci 6:743-749
12. Balaban RS, Nemoto S, Finkel T (2005) Mitochondria, oxidants, and aging. Cell 120(4):483-495
13. Bao Z, Lim S, Liao W, Lin Y, Thiemermann C, Leung BP et al (2007) Glycogen synthase kinase-3beta inhibition attenuates asthma in mice. Am J Respir Crit Care Med 176:431-438
14. Beasley CL, Pennington K, Behan A, Wait R, Dunn MJ, Cotter D (2006) Proteomic analysis of the anterior cingulate cortex in the major psychiatric disorders: evidence for disease-associated changes. Proteomics 6(11):3414-3425
15. Beaulieu JM, Zhang X, Rodriguiz RM, Sotnikova TD, Cools MJ, Wetsel WC, Gainetdinov RR, Caron MG (2008) Role of GSK3beta in behavioural abnormalities induced by serotonin deficiency. Proc Natl Acad Sci USA 105:1333-1338
16. Beckman KB, Ames BN (1996) Detection and quantification of oxidative adducts of mitochondrial DNA. Methods Enzymol 264:442-453
17. Ben-Shachar D, Karry R (2008) Neuroanatomical pattern of mito-chondrial complex I pathology varies between schizophrenia, bipolar disorder and major depression. PLoS One 3(11):e3676
18. Berk M, Wadee AA, Kuschke RH, O'Neill-Kerr A (1997) Acute phase proteins in major depression. J Psychosom Res 43(5): 529-534
19. Berk M, Mitchell VS, Plein H (1998) The platelet intracellular calcium response to serotonin in subsyndromal depression. Int Clin Psychopharmacol 13(3):107-110
20. Berk M, Plein H, Ferreira D (2001) Platelet glutamate receptor supersensitivity in major depressive disorder. Clin Neurophar-macol 24(3):129-132
21. Berk M, Copolov DL, Dean O, Lu K, Jeavons S, Schapkaitz I, Anderson-Hunt M, Bush AI (2008) N-Acetyl cysteine for depressive symptoms in bipolar disorder-a double-blind randomized placebo-controlled trial. Biol Psychiatry 64(6):468-475
22. Berk M, Dean O, Cotton SM, Gama CS, Kapczinski F, Fernandes BS, Kohlmann K, Jeavons S, Hewitt K, Allwang C, Cobb H, Bush AI, Schapkaitz I, Dodd S, Malhi GS (2011a) The efficacy of N-acetylcysteine as an adjunctive treatment in bipolar depression: an open label trial. J Affect Disord 135(1-3):389-394
23. Berk M, Kapczinski F, Andreazza AC, Dean OM, Giorlando F, Maes M, Yücel M, Gama CS, Dodd S, Dean B, Magalhães PV, Amminger P, McGorry P, Malhi GS (2011b) Pathways underlying neuroprogression in bipolar disorder: focus on inflammation, oxidative stress and neurotrophic factors. Neuro-sci Biobehav Rev 35(3):804-817
24. Beurel E (2011) Regulation by glycogen synthase kinase-3 of inflammation and T cells in CNS diseases. Front Mol Neurosci 4:18
25. Beurel E, Jope RS (2008) Differential regulation of STAT family members by glycogen synthase kinase-3. J Biol Chem 283:21934-21944
26. Beurel E, Jope RS (2010) Glycogen synthase kinase-3 regulates inflammatory tolerance in astrocytes. Neuroscience 169(3):1063-1070
27. Bilici M, Efe H, Köroǧlu MA, Uydu HA, Bekaroǧlu M, Deǧer O (2001) Antioxidative enzyme activities and lipid peroxidation in major depression: alterations by antidepressant treatments. J Affect Disord 64(1):43-51
28. Bjarnason I, Takeuchi K (2009) Intestinal permeability in the pathogenesis of NSAID-induced enteropathy. J Gastroenterol 44(Suppl 19):23-29
29. Bonaccorso S, Marino V, Puzella A, Pasquini M, Biondi M, Artini M, Almerighi C, Verkerk R, Meltzer H, Maes M (2002) Increased depressive ratings in patients with hepatitis C receiving interferon-alpha-based immunotherapy are related to inter-feron-alpha-induced changes in the serotonergic system. J Clin Psychopharmacol 22(1):86-90
30. Boyle JJ, Johns M, Lo J, Chiodini A, Ambrose N, Evans PC, Mason JC, Haskard DO (2011) Heme induces heme oxygenase 1 via Nrf2: role in the homeostatic macrophage response to intrapl-aque hemorrhage. Arterioscler Thromb Vasc Biol 31(11):2685-2691
31. Brand MD, Nicholls DG (2011) Assessing mitochondrial dysfunction in cells. Biochem J 435(2):297-312
32. Brown ES, Woolston D, Frol A, Bobadilla L, Khan DA, Hanczyc M, Rush AJ, Fleckenstein J, Babcock E, Cullum CM (2004) Hippocampal volume, spectroscopy, cognition, and mood in patients receiving corticosteroid therapy. Biol Psychiatry 55(5):538-545
33. Brustolim D, Ribeiro-dos-Santos R, Kast RE, Altschuler EL, Soares MB (2006) A new chapter opens in anti-inflammatory treatments: the antidepressant bupropion lowers production of tumor necrosis factor-alpha and interferon-gamma in mice. Int Immu-nopharmacol 6(6):903-907
34. Búrigo M, Roza CA, Bassani C, Fagundes DA, Rezin GT, Feier G, Dal-Pizzol F, Quevedo J, Streck EL (2006) Effect of electro-convulsive shock on mitochondrial respiratory chain in rat brain. Neurochem Res 31(11):1375-1379
35. Butler MG, Dasouki M, Bittel D, Hunter S, Naini A, DiMauro S (2003) Coenzyme Q10 levels in Prader-Willi syndrome: comparison with obese and non-obese subjects. Am J Med Genet A 119A(2):168-171
36. Calkins MJ, Jakel RJ, Johnson DA, Chan K, Kan YW, Johnson JA (2005) Protection from mitochondrial complex II inhibition in vitro and in vivo by Nrf2-mediated transcription. Proc Natl Acad Sci USA 102(1):244-249
37. Campbell S, MacQueen G (2006) An update on regional brain volume differences associated with mood disorders. Curr Opin Psychiatry 19(1):25-33
38. Cantley LC (2002) The phosphoinositide 3-kinase pathway. Science 296:1655-1657
39. Catena-Dell'Osso M, Bellantuono C, Consoli G, Baroni S, Rotella F, Marazziti D (2011) Inflammatory and neurodegenerative pathways in depression: a new avenue for antidepressant development? Curr Med Chem 18(2):245-255
40. Chen G, Huang LD, Jiang YM, Manji HK (1999) The mood-stabilizing agent valproate inhibits the activity of glycogen synthase kinase-3. J Neurochem 72(3):1327-1330
41. Chen K, Gunter K, Maines MD (2000) Neurons overexpressing heme oxygenase-1 resist oxidative stress-mediated cell death. J Neuro-chem 75:304-312
42. Chen G, Shi J, Hu Z et al (2008) Inhibitory effect on cerebral inflammatory response following traumatic brain injury in rats: a potential neuroprotective mechanism of N-acetylcysteine. Mediators Inflamm 2008:716458
43. Chen Y, Jiang T, Chen P, Ouyang J, Xu G, Zeng Z, Sun Y (2011) Emerging tendency towards autoimmune process in major depressive patients: a novel insight from Th17 cells. Psychiatry Res 188(2):224-230
44. Connor TJ, Song C, Leonard BE, Merali Z, Anisman H (1998) An assessment of the effects of central interleukin-1beta,-2,-6, and tumor necrosis factor-alpha administration on some behavioural, neurochemical, endocrine and immune parameters in the rat. Neuroscience 84(3):923-933
45. Correa F, Mallard C, Nilsson M, Sandberg M (2011) Activated microglia decrease histone acetylation and Nrf2-inducible anti-oxidant defence in astrocytes: restoring effects of inhibitors of HDACs, p38 MAPK and GSK3b. Neurobiol Dis 44:142-151
46. Crane FL (2001) Biochemical functions of coenzyme Q10. J Am Coll Nutr 20(6):591-598
47. Cumurcu BE, Ozyurt H, Etikan I, Demir S, Karlidag R (2009) Total antioxidant capacity and total oxidant status in patients with major depression: impact of antidepressant treatment. Psychiatry Clin Neurosci 63(5):639-645
48. Cuzzocrea S, Crisafulli C, Mazzon E, Esposito E, Muia C, Abdelrahman M et al (2006a) Inhibition of glycogen synthase kinase-3beta attenuates the development of carrageenan-induced lung injury in mice. Br J Pharmacol 149:687-702
49. Cuzzocrea S, Genovese T, Mazzon E, Crisafulli C, Di Paola R, Muia C et al (2006b) Glycogen synthase kinase-3 beta inhibition reduces secondary damage in experimental spinal cord trauma. J Pharmacol Exp Ther 318:79-89
50. Cuzzocrea S, Mazzon E, Di Paola R, Muia C, Crisafulli C, Dugo L et al (2006c) Glycogen synthase kinase-3beta inhibition attenuates the degree of arthritis caused by type II collagen in the mouse. Clin Immunol 120:57-67
51. Cuzzocrea S, Di Paola R, Mazzon E, Crisafulli C, Genovese T, Muia C et al (2007a) Glycogen synthase kinase 3beta inhibition reduces the development of nonseptic shock induced by zymosan in mice. Shock 27:97-107
52. Cuzzocrea S, Genovese T, Mazzon E, Esposito E, Muia C, Abdelrahman M et al (2007b) Glycogen synthase kinase-3beta inhibition attenuates the development of Bleomycin-induced lung injury. Int J Immunopathol Pharmacol 20:619-630
53. Cuzzocrea S, Mazzon E, Esposito E, Muia C, Abdelrahman M, Di Paola R et al (2007c) Glycogen synthase kinase-3beta inhibition attenuates the development of ischaemia/reperfusion injury of the gut. Intense Care Med 33:880-893
54. Daley-Yates PT, Powell AP, Smith LL (1988) Pulmonary indole-amine 2,3-dioxygenase activity and its significance in the response of rats, mice, and rabbits to oxidative stress. Toxicol Appl Pharmacol 96(2):222-232
55. Dang H, Chen Y, Liu X, Wang Q, Wang L, Jia W, Wang Y (2009) Antidepressant effects of ginseng total saponins in the forced swimming test and chronic mild stress models of depression. Prog Neuropsychopharmacol Biol Psychiatry 33(8):1417-1424
56. De Sarno P, Axtell RC, Raman C, Roth KA, Alessi DR, Jope RS (2008) Lithium reverts and ameliorates experimental autoimmune encephalomyelitis. J Immunol 181:338-345
57. de Vries HE, Witte M, Hondius D, Rozemuller AJ, Drukarch B, Hoozemans J, van Horssen J (2008) Nrf2-induced antioxidant protection: a promising target to counteract ROS-mediated damage in neurodegenerative disease? Free Radic Biol Med 45(10):1375-1383
58. Dean O, Giorlando F, Berk M (2011) N-Acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action. J Psychiatry Neurosci 36(2):78-86
59. Dimopoulos N, Piperi C, Psarra V, Lea RW, Kalofoutis A (2008) Increased plasma levels of 8-iso-PGF2alpha and IL-6 in an elderly population with depression. Psychiatry Res 161(1):59-66
60. Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctôt KL (2010) A meta-analysis of cytokines in major depression. Biol Psychiatry 67(5):446-457
61. Dragicevic N, Bradshaw PC, Mamcarz M, Lin X, Wang L, Cao C, Arendash GW (2011) Long-term electromagnetic field treatment enhances brain mitochondrial function of both Alzheimer's transgenic mice and normal mice: a mechanism for electromagnetic field-induced cognitive benefit? Neuroscience 185:135-149
62. Dubovsky S (2010) Depression is an inflammatory disease. J Watch Psychiatry 67:446
63. Dugo L, Abdelrahman M, Murch O, Mazzon E, Cuzzocrea S, Thiemermann C (2006) Glycogen synthase kinase-3beta inhibitors protect against the organ injury and dysfunction caused by hemorrhage and resuscitation. Shock 25:485-491
64. Duman RS (2004) Depression: a case of neuronal life and death? Biol Psychiatry 56(3):140-145
65. Dutton PL, Ohnishi T, Darrouzet E, Leonard MA, Sharp RE, Cibney BR, Daldal F, Moser CC (2000) Coenzyme Q oxidation reduction reactions in mitochondrial electron transport. In: Kagan VE, Quinn PJ (eds) Coenzyme Q: molecular mechanisms in health and disease. CRC Press, Boca Raton, pp 65-82
66. Dwivedi Y, Rizavi HS, Roberts RC, Conley RC, Tamminga CA, Pandey GN (2011) Reduced activation and expression of ERK1/2 MAP kinase in the post-mortem brain of depressed suicide subjects. J Neurochem 77(3):916-928
67. Edwards R, Peet M, Shay J, Horrobin D (1998) Omega-3 polyunsat-urated fatty acid levels in the diet and in red blood cell membranes of depressed patients. J Affect Disord 48(2-3):149-155
68. Eren I, Naziroglu M, Demirdas A (2007a) Protective effects of lamotrigine, aripiprazole and escitalopram on depression-induced oxidative stress in rat brain. Neurochem Res 32(7): 1188-1195
69. Eren I, Naziroglu M, Demirdas A, Celik O, Uguz AC, Altunbasak A, Ozmen I, Uz E (2007b) Venlafaxine modulates depression-induced oxidative stress in brain and medulla of rat. Neurochem Res 32(3):497-505
70. Fattal O, Budur K, Vaughan AJ, Franco K (2006) Review of the literature on major mental disorders in adult patients with mitochondrial diseases. Psychosomatics 47(1):1-7
71. Fišar Z, Hroudová J (2010) Intracellular signalling pathways and mood disorders. Folia Biol (Praha) 56(4):135-148
72. 0-deoxyguanosine in clinical depression. Psychosom Med 68(1): 1-7
73. Fuchs E, Czeh B, Kole MH, Michaelis T, Lucassen PJ (2004) Alterations of neuroplasticity in depression: the hippocampus and beyond. Eur Neuropsychopharmacol 14(Suppl 5):S481-S490
74. Gałecki P, Szemraj J, Bieńkiewicz M, Zboralski K, Gałecka E (2009a) Oxidative stress parameters after combined fluoxetine and acetylsalicylic acid therapy in depressive patients. Hum Psychopharmacol 24:277-286
75. Gałecki P, Szemraj J, Bieńkiewicz M, Florkowski A, Gałecka E (2009b) Lipid peroxidation and antioxidant protection in patients during acute depressive episodes and in remission after fluox-etine treatment. Pharmacol Rep 61(3):436-447
76. Gao HK, Yin Z, Zhou N, Feng XY, Gao F, Wang HC (2008) Glycogen synthase kinase-3 inhibition protects the heart from acute ischemia-reperfusion injury via inhibition of inflammation and apoptosis. J Cardiovasc Pharmacol 52:286-292
77. Garcia LS, Comim CM, Valvassori SS, Réus GZ, Barbosa LM, Andreazza AC, Stertz L, Fries GR, Gavioli EC, Kapczinski F, Quevedo J (2008) Acute administration of ketamine induces antidepressant-like effects in the forced swimming test and increases BDNF levels in the rat hippocampus. Prog Neuropsy-chopharmacol Biol Psychiatry 32(1):140-144
78. Gardner A, Boles RG (2008a) Symptoms of somatization as a rapid screening tool for mitochondrial dysfunction in depression. Biopsychosoc Med 2:7
79. Gardner A, Boles RG (2008b) Mitochondrial energy depletion in depression with somatization. Psychother Psychosom 77(2):127-129
80. Gardner A, Boles RG (2011) Beyond the serotonin hypothesis: mitochondria, inflammation and neurodegeneration in major depression and affective spectrum disorders. Prog. Neuro Psychopharmacol Biol Psychiatry 35(3):730-743
81. Gardner A, Johansson A, Wibom R, Nennesmo I, von Döbeln U, Hagenfeldt L, Hällström T (2003) Alterations of mitochondrial function and correlations with personality traits in selected major depressive disorder patients. J Affect Disord 76(1-3):55-68
82. Gawryluk JW, Wang JF, Andreazza AC, Shao L, Yatham LN, Young LT (2011) Prefrontal cortex glutathione S-transferase levels in patients with bipolar disorder, major depression and schizophrenia. Int J Neuropsychopharmacol 14(8):1069-1074
83. Gere-Paszti E, Jakus J (2009) The effect of N-acetylcysteine on amphetamine-mediated dopamine release in rat brain striatal slices by ion-pair reversed-phase high performance liquid chromatography. Biomed Chromatogr 23:658-664
84. Gould TD, Manji HK (2005) Glycogen synthase kinase-3: a putative molecular target for lithium mimetic drugs. Neuropsychophar-macology 30:1223-1237
85. Gould TD and Manji HK (2006) Glycogen synthase kinase 3: a target for novel mood disorder treatments. In: Wang B (ed) Glycogen synthase kinase 3 (GSK-3) and its inhibitors-drug discovery and development, Chap 7. Wiley Series in Drug Discovery and Development, New Jersey, pp 125-154
86. Greco T, Fiskum G (2010) Neuroprotection through stimulation of mitochondrial antioxidant protein expression. J Alzheimers Dis 20(Suppl 2):S427-S437
87. Guha M, Mackman N (2002) The phosphatidylinositol 3-kinase-Akt pathway limits lipopolysaccharide activation of signaling pathways and expression of inflammatory mediators in human monocytic cells. J Biol Chem 277:32124-32132
88. Gutiérrez-Pérez A, Cortés-Rojo C, Noriega-Cisneros R, Calderón-Cortés E, Manzo-Avalos S, Clemente-Guerrero M, Godinez-Hernández D, Boldogh I, Saavedra-Molina A (2011) Protective effects of resveratrol on calcium-induced oxidative stress in rat heart mitochondria. J Bioenerg Biomembr 43(2):101-107
89. Halestrap AP, McStay GP, Clarke SJ (2002) The permeability transition pore complex: another view. Biochimie 84(2-3):153-166
90. Halestrap AP, Clarke SJ, Javadov SA (2004) Mitochondrial permeability transition pore opening during myocardial reperfusion-a target for cardioprotection. Cardiovasc Res 61(3):372-385
91. Hannestad J, Dellagioia N, Bloch M (2011) The effect of antidepres-sant medication treatment on serum levels of inflammatory cytokines: a meta-analysis. Neuropsychopharmacology 36(12): 2452-2459
92. Harvey CJ, Thimmulappa RK, Singh A, Blake DJ, Ling G, Wakabayashi N, Fujii J, Myers A, Biswal S (2009) Nrf2-regulated glutathione recycling independent of biosynthesis is critical for cell survival during oxidative stress. Free Radic Biol Med 46(4):443-445
93. Hashioka S, Klegeris A, Monji A, Kato T, Sawada M, McGeer PL, Kanba S (2007) Antidepressants inhibit interferon-gamma-induced microglial production of IL-6 and nitric oxide. Exp Neurol 206(1):33-42
94. Herken H, Gurel A, Selek S, Armutcu F, Ozen ME, Bulut M, Kap O, Yumru M, Savas HA, Akyol O (2007) Adenosine deaminase, nitric oxide, superoxide dismutase, and xanthine oxidase in patients with major depression: impact of antidepressant treatment. Arch Med Res 38(2):247-252
95. Hoeflich KP, Luo J, Rubie EA, Tsao MS, Jin O, Woodgett JR (2000) Requirement for glycogen synthase kinase-3beta in cell survival and NF-kappaB activation. Nature 406:86-90
96. Hroudová J, Fišar Z (2011) Connectivity between mitochondrial functions and psychiatric disorders. Psychiatry Clin Neurosci 65(2):130-141
97. Hu X, Paik PK, Chen J, Yarilina A, Kockeritz L, Lu TT et al (2006) IFN-gamma suppresses IL-10 production and synergizes with TLR2 by regulating GSK3 and CREB/AP-1 proteins. Immunity 24:563-574
98. Huang WC, Lin YS, Wang CY, Tsai CC, Tseng HC, Chen CL, Lu PJ, Chen PS, Qian L, Hong JS, Lin CF (2009) Glycogen synthase kinase-3 negatively regulates anti-inflammatory interleukin-10 for lipopolysaccharide-induced iNOS/NO biosynthesis and RANTES production in microglial cells. Immunology 128(1 Suppl):e275-e286
99. Hubbs AF, Benkovic SA, Miller DB, O'Callaghan JP, Battelli L, Schwegler-Berry D, Ma Q (2007) Vacuolar leukoencephalopa-thy with widespread astrogliosis in mice lacking transcription factor Nrf2. Am J Pathol 170(6):2068-2076
100. Hunter RL, Dragicevic N, Seifert K, Choi DY, Liu M, Kim HC, Cass WA, Sullivan PG, Bing G (2007) Inflammation induces mito-chondrial dysfunction and dopaminergic neurodegeneration in the nigrostriatal system. J Neurochem 100(5):1375-1386
101. Hybertson BM, Gao B, Bose SK, McCord JM (2011) Oxidative stress in health and disease: the therapeutic potential of Nrf2 activation. Mol Aspects Med 2011 Oct 15 (Epub ahead of print)
102. Innamorato NG, Rojo AI, García-Yagüe AJ, Yamamoto M, de Ceballos ML, Cuadrado A (2008) The transcription factor Nrf2 is a therapeutic target against brain inflammation. J Immunol 181(1):680-689
103. Irie M, Miyata M, Kasai H (2005) Depression and possible cancer risk due to oxidative DNA damage. J Psychiatr Res 39(6):553-560
104. Itoh K, Chiba T, Takahashi S, Ishii T, Igarashi K, Katoh Y, Oyake T, Hayashi N, Satoh K, Hatayama I, Yamamoto M, Nabeshima Y (1997) An Nrf2/small Maf heterodimer mediates the induction of phase II detoxifying enzyme genes through antioxidant response elements. Biochem Biophys Res Commun 236(2):313-322
105. Ivanov II, Mckenzie BS, Zhou L, Tadokoro CE, Lepelley A, Lafaille JJ, Cua DJ, Littman DR (2006) The orphan nuclear receptor RORgammat directs the differentiation program of proinflam-matory IL-17 ? Thelper cells. Cell 126:1121-1133
106. Jain AK, Jaiswal AK (2007) GSK-3b acts upstream of Fyn kinase in regulation of nuclear export and degradation of NF-E2 related factor 2. J Biol Chem 282(22):16502-16510
107. Jeng JY, Lee WH, Tsai YH, Chen CY, Chao SY, Hsieh RH (2009) Functional modulation of mitochondria by eicosapentaenoic acid provides protection against ceramide toxicity to C6 glioma cells. J Agric Food Chem 57(24):11455-11462
108. Jiang Y, Deacon R, Anthony DC, Campbell SJ (2008) Inhibition of peripheral TNF can block the malaise associated with CNS inflammatory diseases. Neurobiol Dis 32(1):125-132
109. Jimerson DC, Post RM, Carman JS, van Kammen DP, Wood JH, Goodwin FK, Bunney WE Jr (1979) CSF calcium: clinical correlates in affective illness and schizophrenia. Biol Psychiatry 14(1):37-51
110. Johnson JA, Johnson DA, Kraft AD, Calkins MJ, Jakel RJ, Vargas MR, Chen PC (2008) The Nrf2-ARE pathway: an indicator and modulator of oxidative stress in neurodegeneration. Ann NY Acad Sci 1147:61-69
111. Jones SP, Teshima Y, Akao M, Marbán E (2003) Simvastatin attenuates oxidant-induced mitochondrial dysfunction in cardiac myocytes. Circ Res 93(8):697-699
112. Jope RS (1999) Anti-bipolar therapy: mechanism of action of lithium. Mol Psychiatry 4(2):117-128
113. Jope RS (2011) Glycogen synthase kinase-3 in the etiology and treatment of mood disorders. Front Mol Neurosci 4:16
114. Jou SH, Chiu NY, Liu CS (2009) Mitochondrial dysfunction and psychiatric disorders. Chang Gung Med J 32(4):370-379
115. Kahl KG, Kruse N, Faller H, Weiss H, Rieckmann P (2002) Expression of tumor necrosis factor-alpha and interferon-gamma mRNA in blood cells correlates with depression scores during an acute attack in patients with multiple sclerosis. Psychoneuroen-docrinology 27(6):671-681
116. Kaidanovich-Beilin O, Milman A, Weizman A, Pick CG, Eldar-Finkelman H (2004) Rapid antidepressive-like activity of specific glycogen synthase kinase-3 inhibitor and its effect on beta-catenin in mouse hippocampus. Biol Psychiatry 55(8):781-784
117. Kanninen K, White AR, Koistinaho J, Malm T (2011) Targeting glycogen synthase kinase-3b for therapeutic benefit against oxidative stress in Alzheimer's disease: involvement of the Nrf2-ARE pathway. Int J Alzheimers Dis 2011:985085
118. Karry R, Klein E, Ben Shachar D (2004) Mitochondrial complex I subunits expression is altered in schizophrenia: a postmortem study. Biol Psychiatry 55:676-684
119. Kaspar JW, Niture SK, Jaiswal AK (2009) Nrf2:INrf2 (Keap1) signaling in oxidative stress. Free Radic Biol Med 47:1304-1309
120. Kato T (2007) Mitochondrial dysfunction as the molecular basis of bipolar disorder: therapeutic implications. CNS Drugs 21(1): 1-11
121. Kato T (2008) Role of mitochondrial DNA in calcium signaling abnormality in bipolar disorder. Cell Calcium 44(1):92-102
122. Kato T, Kato N (2000) Mitochondrial dysfunction in bipolar disorder. Bipolar Disord 2(3 Pt 1):180-190
123. Katyare SS, Rajan RR (1995) Effect of long-term in vivo treatment with imipramine on the oxidative energy metabolism in rat brain mitochondria. Comp Biochem Physiol C Pharmacol Toxicol Endocrinol 112(3):353-357
124. Khan M, Sekhon B, Jatana M et al (2004) Administration of N-acetylcysteine after focal cerebral ischemia protects brain and reduces inflammation in a rat model of experimental stroke. J Neurosci Res 76:519-527
125. Khanzode SD, Dakhale GN, Khanzode SS, Saoji A, Palasodkar R (2003) Oxidative damage and major depression: the potential antioxidant action of selective serotonin re-uptake inhibitors. Redox Rep 8(6):365-370
126. Kirsch I (2009) Antidepressants and the placebo response. Epidemiol Psychiatr Soc 18(4):318-322
127. Klein PS, Melton DA (1996) A molecular mechanism for the effect of lithium on development. Proc Natl Acad Sci USA 93(16):8455-8459
128. Klementiev B, Novikova T, Novitskaya V, Walmod PS, Dmytriyeva O, Pakkenberg B, Berezin V, Bock E (2007) A neural cell adhesion molecule-derived peptide reduces neuropathological signs and cognitive impairment induced by Abeta25-35. Neuro-science 145(1):209-224
129. Kodydková J, Vávrová L, Zeman M, Jirák R, Macásek J, Stanková B, Tvrzická E, Zák A (2009) Antioxidative enzymes and increased oxidative stress in depressive women. Clin Biochem 42(13-14): 1368-1374
130. Koo JW, Duman RS (2008) IL-1beta is an essential mediator of the antineurogenic and anhedonic effects of stress. Proc Natl Acad Sci USA 105(2):751-756
131. Kroemer G, Zamzami N, Susin SA (1997) Mitochondrial control of apoptosis. Immunol Today 18(1):44-51
132. Kubera M, Symbirtsev A, Basta-Kaim A, Borycz J, Roman A, Papp M, Claesson M (1996) Effect of chronic treatment with imipramine on interleukin 1 and interleukin 2 production by splenocytes obtained from rats subjected to a chronic mild stress model of depression. Pol J Pharmacol 48(5):503-506
133. Kubera M, Holan V, Mathison R, Maes M (2000a) The effect of repeated amitriptyline and desipramine administration on cyto-kine release in C57BL/6 mice. Psychoneuroendocrinology 25(8):785-797
134. Kubera M, Kenis G, Bosmans E, Zieba A, Dudek D, Nowak G, Maes M (2000b) Plasma levels of interleukin-6, interleukin-10, and interleukin-1 receptor antagonist in depression: comparison between the acute state and after remission. Pol J Pharmacol 52(3):237-241
135. Kubera M, Simbirtsev A, Mathison R, Maes M (2000c) Effects of repeated fluoxetine and citalopram administration on cytokine release in C57BL/6 mice. Psychiatry Res 96(3):255-266
136. Kubera M, Obuchowicz E, Goehler L, Brzeszcz J, Maes M (2011) In animal models, psychosocial stress-induced (neuro)inflamma-tion, apoptosis and reduced neurogenesis are associated to the onset of depression. Prog Neuropsychopharmacol Biol Psychiatry 35(3):744-759
137. Kulkarni S, Dhir A, Akula KK (2009) Potentials of curcumin as an antidepressant. Sci World J 9:1233-1241
138. Kumar P, Kumar A (2009) Possible role of sertraline against 3-nitropropionic acid induced behavioral, oxidative stress and mitochondrial dysfunctions in rat brain. Prog Neuropsychophar-macol Biol Psychiatry 33(1):100-108
139. Lai J, Moxey A, Nowak G, Vashum K, Bailey K, McEvoy M (2011) The efficacy of zinc supplementation as therapy for depression: systematic review of randomized controlled trials. J Affect Disord. doi:10.1016/j.jad.2011.06.022
140. Langsjoen PH, Langsjoen JO, Langsjoen AM, Lucas LA (2005) Treatment of statin adverse effects with supplemental Coenzyme Q10 and statin drug discontinuation. Biofactors 25(1-4): 147-152
141. Lanquillon S, Krieg JC, Bening-Abu-Shach U, Vedder H (2000) Cytokine production and treatment response in major depressive disorder. Neuropsychopharmacology 22(4):370-379
142. Lante F, Meunier J, Guiramand J et al (2008) Late N-acetylcysteine treatment prevents the deficits induced in the offspring of dams exposed to an immune stress during gestation. Hippocampus 18:602-609
143. Leconte C, Bihel E, Lepelletier FX, Bouët V, Saulnier R, Petit E, Boulouard M, Bernaudin M, Schumann-Bard P (2011) Comparison of the effects of erythropoietin and its carbamylated derivative on behaviour and hippocampal neurogenesis in mice. Neuropharmacology 60(2-3):354-364
144. Lee KM, Kim YK (2006) The role of IL-12 and TGF-beta1 in the pathophysiology of major depressive disorder. Int Immunophar-macol 6(8):1298-1304
145. Lee JS, Surh YJ (2005) Nrf2 as a novel molecular target for chemoprevention. Cancer Lett 224(2):171-184
146. Lee JM, Shih AY, Murphy TH, Johnson JA (2003) NF-E2-related factor-2 mediates neuroprotection against mitochondrial complex I inhibitors and increased concentrations of intracellular calcium in primary cortical neurons. J Biol Chem 278(39):37948-37956
147. Lemasters JJ, Nieminen AL, Qian T, Trost LC, Elmore SP, Nishimura Y, Crowe RA, Cascio WE, Bradham CA, Brenner DA, Herman B (1998) The mitochondrial permeability transition in cell death: a common mechanism in necrosis, apoptosis and autophagy. Biochim Biophys Acta 1366(1-2):177-196
148. Lenox RH, Hahn CG (2000) Overview of the mechanism of action of lithium in the brain: fifty-year update. J Clin Psychiatry 61(Suppl 9):5-15
149. Leonard BE, Maes M (2011) Mechanistic explanations how activated inflammatory, oxidative and nitrosative stress pathways cause depression. Neurosci Biobehav Rev (Epub ahead of print)
150. Li X, Bijur GN, Jope RS (2002) Glycogen synthase kinase-3beta, mood stabilizers, and neuroprotection. Bipolar Disord 4(2):137-144
151. Li X, Zhu W, Roh MS, Friedman AB, Rosborough K, Jope RS (2004) In vivo regulation of glycogen synthase kinase-3beta (GSK3beta) by serotonergic activity in mouse brain. Neuropsy-chopharmacology 29:1426-1431
152. Li X, Rosborough KM, Friedman AB, Zhu W, Roth KA (2007) Regulation of mouse brain glycogen synthase kinase-3 by atypical antipsychotics. Int J Neuropsychopharmacol 10:7-19
153. Lin PY, Su KP (2007) A meta-analytic review of double-blind, placebo-controlled trials of antidepressant efficacy of omega-3 fatty acids. J Clin Psychiatry 68(7):1056-1061
154. Lipton P (1999) Ischemic cell death in brain neurons. Physiol Rev 79(4):1431-1568
155. Li-Smerin Y, Levitan ES, Johnson JW (2001) Free intracellular Mg(2+) concentration and inhibition of NMDA responses in cultured rat neurons. J Physiol 533:729-743
156. Loix S, De Kock M, Henin P (2011) The anti-inflammatory effects of ketamine: state of the art. Acta Anaesthesiol Belg 62(1):47-58
157. Lorenzetti V, Allen NB, Fornito A, Yucel M (2009) Structural brain abnormalities in major depressive disorder: a selective review of recent MRI studies. J Affect Disord 117(1-2):1-17
158. Luchetti F, Canonico B, Betti M, Arcangeletti M, Pilolli F, Piroddi M, Canesi L, Papa S, Galli F (2010) Melatonin signaling and cell protection function. FASEB J 24(10):3603-3624
159. MacAulay K, Woodgett JR (2008) Targeting glycogen synthase kinase-3 (GSK-3) in the treatment of type 2 diabetes. Expert Opin Ther Targets 12(10):1265-1274
160. Machado-Vieira R, Manji HK, Zarate CA Jr (2009) The role of lithium in the treatment of bipolar disorder: convergent evidence for neurotrophic effects as a unifying hypothesis. Bipolar Disord 11(Suppl 2):92-109
161. Maes M (1995) Evidence for an immune response in major depression: a review and hypothesis. Prog Neuropsychopharma-col Biol Psychiatry 19(1):11-38
162. Maes M (2011) Depression is an inflammatory disease, but cell-mediated immune activation is the key component of depression. Prog Neuropsychopharmacol Biol Psychiatry 35(3):664-675
163. Maes M, Meltzer HY (1995) The serotonin hypothesis of major depression. selected chapters on mood disorders. In: Bloom F, Kupfer D (eds) Psychopharmacology. The fourth generation of progress. Raven Press, USA, pp 933-944
164. Maes M, Bosmans E, Suy E, Vandervorst C, De Jonckheere C, Raus J (1990) Immune disturbances during major depression: upregu-lated expression of interleukin-2 receptors. Neuropsychobiology 24(3):115-120
165. Maes M, Scharpé 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(3):183-192
166. Maes M, Bosmans E, De Jongh R, Kenis G, Vandoolaeghe E, Neels H (1997a) Increased serum IL-6 and IL-1 receptor antagonist concentrations in major depression and treatment resistant depression. Cytokine 9(11):853-858
167. Maes M, Delange J, Ranjan R, Meltzer HY, Desnyder R, Cooremans W, Scharpé S (1997b) Acute phase proteins in schizophrenia, mania and major depression: modulation by psychotropic drugs. Psychiatry Res 66(1):1-11
168. Maes M, Christophe A, Delanghe J, Altamura C, Neels H, Meltzer HY (1999a) Lowered omega3 polyunsaturated fatty acids in serum phospholipids and cholesteryl esters of depressed patients. Psychiatry Res 85(3):275-291
169. Maes M, Song C, Lin AH, Bonaccorso S, Kenis G, De Jongh R, Bosmans E, Scharpe S (1999b) Negative immunoregulatory effects of antidepressants: inhibition of interferon-gamma and stimulation of interleukin-10 secretion. Neuropsychopharmacol 20(4):370-379
170. Maes M, De Vos N, Pioli R, Demedts P, Wauters A, Neels H, Christophe A (2000) Lower serum vitamin E concentrations in major depression. Another marker of lowered antioxidant defences in that illness. J Affect Disord 58(3):241-246
171. Maes M, Mihaylova I, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E (2009a) Increased 8-hydroxy-deoxyguanosine, a marker of oxidative damage to DNA, in major depression and myalgic encephalomyelitis/chronic fatigue syndrome. Neuro Endocrinol Lett 30(6):715-722
172. Maes M, Mihaylova I, Kubera M, Uytterhoeven M, Vrydags N, Bosmans E (2009b) Lower plasma Coenzyme Q10 in depression: a marker for treatment resistance and chronic fatigue in depression and a risk factor to cardiovascular disorder in that illness. Neuro Endocinol Lett 30:462-469
173. Maes M, Yirmyia R, Noraberg J, Brene S, Hibbeln J, Perini G, Kubera M, Bob P, Lerer B, Maj M (2009c) The inflammatory & neurodegenerative (I&ND) hypothesis of depression: leads for future research and new drug developments in depression. Metab Brain Dis 24(1):27-53
174. MaesM,MihaylovaI,KuberaM,UytterhoevenM,VrydagsN,Bosmans E (2010) Increased plasma peroxides and serum oxidized low density lipoprotein antibodies in major depression: markers that further explain the higher incidence of neurodegeneration and coronary artery disease. J Affect Disord 125(1-3):287-294
175. Maes M, Galecki P, Chang YS, Berk M (2011a) A review on the oxidative and nitrosative stress (O&NS) pathways in major depression and their possible contribution to the (neuro)degen-erative processes in that illness. Prog Neuropsychopharmacol Biol Psychiatry 35(3):676-692
176. Maes M, Leonard B, Fernandez A, Kubera M, Nowak G, Veerhuis R, Gardner A, Ruckoanich P, Geffard M, Altamura C, Galecki P, Berk M (2011b) (Neuro)inflammation and neuroprogression as new pathways and drug targets in depression: from antioxidants to kinase inhibitors. Prog Neuropsychopharmacol Biol Psychiatry 35(3):659-663
177. Maes M, Leonard BE, Myint AM, Kubera M, Verkerk R (2011c) The new '5-HT' hypothesis of depression: cell-mediated immune activation induces indoleamine 2,3-dioxygenase, which leads to lower plasma tryptophan and an increased synthesis of detrimental tryptophan catabolites (TRYCATs), both of which contribute to the onset of depression. Prog Neuropsychophar-macol Biol Psychiatry 35(3):702-721
178. Maes M, Mihaylova I, Kubera M, Leunis JC, Geffard M (2011d) IgM-mediated autoimmune responses directed against multiple neoepitopes in depression: new pathways that underpin the inflammatory and neuroprogressive pathophysiology. J Affect Disord 135(1-3):414-418
179. Maes M, Mihaylova I, Kubera M, Ringel K (2011e) Activation of cell-mediated immunity in depression: association with inflammation, melancholia, clinical staging and the fatigue and somatic symptom cluster of depression. Prog Neuropsychopharmacol Biol Psychiatry. PMID: 21945535 (Epub ahead of print)
180. Maier SF, Watkins LR (1995) Intracerebroventricular interleukin-1 receptor antagonist blocks the enhancement of fear conditioning and interference with escape produced by inescapable shock. Brain Res 695(2):279-282
181. Malberg JE, Monteggia LM (2008) VGF, a new player in antide-pressant action? Sci Signal 1(18):pe19
182. Malhi GS, Berk M (2007) Does dopamine dysfunction drive depression? Acta Psychiatr Scand Suppl 433:116-124
183. Malhi GS, Berk M (2011) Balance restored: lithium remains a safe and sound choice. Lancet (in press)
184. Malhotra D, Portales-Casamar E, Singh A, Srivastava S, Arenillas D, Happel C, Shyr C, Wakabayashi N, Kensler TW, Wasserman WW, Biswal S (2010) Global mapping of binding sites for Nrf2 identifies novel targets in cell survival response through ChIP-Seq profiling and network analysis. Nucleic Acids Res 38(17): 5718-5734
185. Martin M, Rehani K, Jope RS, Michalek SM (2005) Toll-like receptor-mediated cytokine production is differentially regulated by glycogen synthase kinase 3. Nat Immunol 6:777-7784
186. Maurer IC, Schippel P, Volz HP (2009) Lithium-induced enhancement of mitochondrial oxidative phosphorylation in human brain tissue. Bipolar Disord 11(5):515-522
187. McKinnon MC, Yucel K, Nazarov A, MacQueen GM (2009) A meta-analysis examining clinical predictors of hippocampal volume in patients with major depressive disorder. J Psychiatry Neurosci (Meta Anal Rev) 34(1):41-54
188. Medina M, Avila J (2010) Glycogen synthase kinase-3 (GSK-3) inhibitors for the treatment of Alzheimer's disease. Curr Pharm Des 16(25):2790-2798
189. Medina M, Castro A (2008) Glycogen synthase kinase-3 (GSK-3) inhibitors reach the clinic. Curr Opin Drug Discov Dev 11(4): 533-543
190. Medina M, Wandosell FJ (2011) Deconstructing GSK-3: the fine regulation of its activity. Int J Alz Dis 479249. doi:10.4061/2011/479249
191. Medina M, Garrido JJ, Wandosell FJ (2011) Modulation of GSK-3 as a therapeutic strategy on Tau pathologies. Front Mol Neurosci 4:24
192. Michel TM, Camara S, Tatschner T, Frangou S, Sheldrick AJ, Riederer P, Grunblatt E (2008) Increased xanthine oxidase in the thalamus and putamen in depression. World J Biol Psychiatry 12:1-7
193. Miura T, Tanno M, Sato T (2010) Mitochondrial kinase signalling pathways in myocardial protection from ischaemia/reperfusion-induced necrosis. Cardiovasc Res 88(1):7-15
194. Mizuno S, Yamamoto M, Sugawara I (2010) Significant reduction of granulomas in Nrf2-deficient mice infected with Mycobacterium tuberculosis. Indian J Tuberc 57(2):108-113
195. Moghaddam B (2002) Stress activation of glutamate neurotransmis-sion in the prefrontal cortex: implications for dopamine-associated psychiatric disorders. Biol Psychiatry 51(10):775-787
196. Mohr DC, Boudewyn AC, Goodkin DE, Bostrom A, Epstein L (2001a) Comparative outcomes for individual cognitive-behavior therapy, supportive-expressive group psychotherapy, and sertraline for the treatment of depression in multiple sclerosis. J Consult Clin Psychol 69(6):942-949
197. Mohr DC, Goodkin DE, Islar J, Hauser SL, Genain CP (2001b) Treatment of depression is associated with suppression of nonspecific and antigen-specific T(H)1 responses in multiple sclerosis. Arch Neurol 58(7):1081-1086
198. Molina-Hernández M, Tellez-Alcántara NP, Pérez-Garćia J, Olivera-Lopez JI, Jaramillo-Jaimes MT (2008) Antidepressant-like actions of minocycline combined with several glutamate antagonists. Prog Neuropsychopharmacol Biol Psychiatry 32(2):380-386
199. Moncrieff J, Wessely S, Hardy R (2004) Active placebos versus antidepressants for depression. Cochrane Database Syst Rev 1:CD003012
200. Müller N, Schwarz MJ, Dehning S, Douhe A, Cerovecki A, Goldstein-Müller B, Spellmann I, Hetzel G, Maino K, Kleind-ienst N, Möller HJ, Arolt V, Riedel M (2006) 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 11(7):680-684
201. Murphy MP (2009) Mitochondria-a neglected drug target. Curr Opin Investig Drugs 10(10):1022-1024
202. Nahon E, Israelson A, Abu-Hamad S, Varda SB (2005) Fluoxetine (Prozac) interaction with the mitochondrial voltage-dependent anion channel and protection against apoptotic cell death. FEBS Lett 579(22):5105-5110
203. Nerland DE (2007) The antioxidant/electrophile response element motif. Drug Metab Rev 39(1):235-248
204. Nestler EJ, Carlezon WA Jr (2006) The mesolimbic dopamine reward circuit in depression. Biol Psychiatry 59(12):1151-1159
205. Nicholls DG (2008) Oxidative stress and energy crises in neuronal dysfunction. Ann NY Acad Sci 1147:53-60
206. Nowak G, Siwek M, Dudek D, Zieba A, Pilc A (2003) Effect of zinc supplementation on antidepressant therapy in unipolar depression: a preliminary placebo-controlled study. Pol J Pharmacol 55:1143-1147
207. O'Shea JJ, Paul WE (2010) Mechanisms underlying lineage commitment and plasticity of helper CD4? T cells. Science 327:1098-1102
208. O'Brien SM, Scully P, Fitzgerald P, Scott LV, Dinan TG (2007) Plasma cytokine profiles in depressed patients who fail to respond to selective serotonin reuptake inhibitor therapy. J Psychiatr Res 41(3-4):326-331
209. O'Connor JC, André C, Wang Y, Lawson MA, Szegedi SS, Lestage J, Castanon N, Kelley KW, Dantzer R (2009) Interferon-gamma and tumor necrosis factor-alpha mediate the upregulation of indoleamine 2,3-dioxygenase and the induction of depressive-like behavior in mice in response to bacillus Calmette-Guerin. J Neurosci 29(13):4200-4209
210. Owen AJ, Batterham MJ, Probst YC, Grenyer BF, Tapsell LC (2005) Low plasma vitamin E levels in major depression: diet or disease? Eur J Clin Nutr 59(2):304-306
211. Ozcan ME, Gulec M, Ozerol E, Polat R, Akyol O (2004) Antioxidant enzyme activities and oxidative stress in affective disorders. Int Clin Psychopharmacol 19(2):89-95
212. Pae CU, Marks DM, Han C, Patkar AA (2008) Does minocycline have antidepressant effect? Biomed Pharmacother 62(5):308-311
213. Paintlia MK, Paintlia AS, Khan M et al (2008) Modulation of peroxisome proliferator-activated receptor-alpha activity by N-acetyl cysteine attenuates inhibition of oligodendrocyte development in lipo-polysaccharide stimulated mixed glial cultures. J Neurochem 105:956-970
214. Pan H, Wang H, Zhu L, Mao L, Qiao L, Su X (2011) Depletion of nrf2 enhances inflammation induced by oxyhemoglobin in cultured mice astrocytes. Neurochem Res 36(12):2434-2441
215. Pasco JA, Jacka FN, Williams LJ, Henry MJ, Nicholson GC, Kotowicz MA, Berk M (2010) Clinical implications of the cytokine hypothesis of depression: the association between use of statins and aspirin and the risk of major depression. Psychother Psychosom 79(5):323-325
216. Passi S, Stancato A, Aleo E, Dmitrieva A, Littarru GP (2003) Statins lower plasma and lymphocyte ubiquinol/ubiquinone without affecting other antioxidants and PUFA. Biofactors 18(1-4): 113-124
217. Peineau S, Bradley C, Taghibiglou C, Doherty A, Bortolotto ZA, Wang YT, Collingridge GL (2008) The role of GSK-3 in synaptic plasticity. Br J Pharmacol 153:S428-S437
218. Periyasamy S, Sánchez ER (2002) Antagonism of glucocorticoid receptor transactivity and cell growth inhibition by transforming growth factor-beta through AP-1-mediated transcriptional repression. Int J Biochem Cell Biol 34(12):1571-1585
219. Piantadosi CA, Withers CM, Bartz RR, MacGarvey NC, Fu P, Sweeney TE, Welty-Wolf KE, Suliman HB (2011) Heme oxygenase-1 couples activation of mitochondrial biogenesis to anti-inflammatory cytokine expression. J Biol Chem 286(18): 16374-16385
220. Plein H, Berk M (2000) Changes in the platelet intracellular calcium response to serotonin in patients with major depression treated with electroconvulsive therapy: state or trait marker status. Int Clin Psychopharmacol 15(2):93-98
221. Polter AM, Li X (2011) Glycogen synthase kinase-3 is an intermediate modulator of serotonin neurotransmission. Front Mol Neurosci 4:31
222. Popoli M (2009) Agomelatine: innovative pharmacological approach in depression. CNS Drugs 23(Suppl 2):27-34
223. Qian HR, Yang Y (2009) Neuron differentiation and neuritogenesis stimulated by N-acetylcysteine (NAC). Acta Pharmacol Sin 30(7):907-912
224. Quiroz JA, Gray NA, Kato T, Manji HK (2008) Mitochondrially mediated plasticity in the pathophysiology and treatment of bipolar disorder. Neuropsychopharmacology 33(11):2551-2565
225. Ramsey CP, Glass CA, Montgomery MB, Lindl KA, Ritson GP, Chia LA, Hamilton RL, Chu CT, Jordan-Sciutto KL (2007) Expression of Nrf2 in neurodegenerative diseases. J Neuropathol Exp Neurol 66:75-85
226. Rasola A, Sciacovelli M, Chiara F, Pantic B, Brusilow WS, Bernardi P (2010) Activation of mitochondrial ERK protects cancer cells from death through inhibition of the permeability transition. Proc Natl Acad Sci USA 107(2):726-731
227. Ray WJ Jr, Szymanki ES, Ng L (1978) The binding of lithium and of anionic metabolites to phosphoglucomutase. Biochim Biophys Acta 522(2):434-442
228. Rehani K, Wang H, Garcia CA, Kinane DF, Martin M (2009) Tolllike receptor-mediated production of IL-1Ra is negatively regulated by GSK3 via the MAPK ERK1/2. J Immunol 182(1):547-553
229. Rodríguez-Hernández A, Cordero MD, Salviati L, Artuch R, Pineda M, Briones P, Gómez Izquierdo L, Cotán D, Navas P, Sánchez-Alcázar JA (2009) Coenzyme Q deficiency triggers mitochondria degradation by mitophagy. Autophagy 5(1):19-32
230. Rojo AI, Rada P, Egea J, Rosa AO, Lopez MG, Cuadrado A (2008a) Functional interference between glycogen synthase kinase-3 beta and the transcription factor Nrf2 in protection against kainate-induced hippocampal cell death. Mol Cell Neurosci 39:125-132
231. Rojo AI, Sagarra MR, Cuadrado A (2008b) GSK-3b down-regulates the transcription factor Nrf2 after oxidant damage: relevance to exposure of neuronal cells to oxidative stress. J Neurochem 105(1):192-202
232. Romeo L, Intrieri M, D'Agata V, Mangano NG, Oriani G, Ontario ML, Scapagnini G (2009) The major green tea polyphenol, (-)-epigallocatechin-3- gallate, induces heme oxygenase in rat neurons and acts as an effective neuroprotective agent against oxidative stress. J Am Coll Nutr 28(Suppl):492S-499S
233. Rosa AO, Kaster MP, Binfaré RW, Morales S, Martín-Aparicio E, Navarro-Rico ML, Martínez A, Medina M, Garćia AG, Lopez MG, Rodrigues ALS (2008) Antidepressant-like effects of the novel thiadiazolidinone NP031115 in mice. Prog Neuro Psy-chopharm Biol Psychiatry 32:1549-1556
234. Rosenberg G (2007) The mechanisms of action of valproate in neuropsychiatric disorders: can we see the forest for the trees? Cell Mol Life Sci 64(16):2090-2103
235. Rowe MK, Wiest C, Chuang DM (2007) GSK-3 is a viable potential target for therapeutic intervention in bipolar disorder. Neurosci Biobehav Rev 31:920-931
236. Sachdeva AK, Kuhad A, Chopra K (2011) Epigallocatechin gallate ameliorates behavioral and biochemical deficits in rat model of load-induced chronic fatigue syndrome. Brain Res Bull 86(3-4):165-172
237. Sakić B, Szechtman H, Braciak T, Richards C, Gauldie J, Denburg JA (1997) Reduced preference for sucrose in autoimmune mice: a possible role of interleukin-6. Brain Res Bull 44(2):155-165
238. Sakić B, Gauldie J, Denburg JA, Szechtman H (2001) Behavioral effects of infection with IL-6 adenovector. Brain Behav Immun 15(1):25-42
239. Samavati L, Rastogi R, Du W, Huttemann M, Fite A, Franchi L (2009) STAT3 tyrosine phosphorylation is critical for interleukin 1 beta and interleukin-6 production in response to lipopolysac-charide and live bacteria. Mol Immunol 46:1867-1877
240. Sandi C (2004) Stress, cognitive impairment and cell adhesion molecules. Nat Rev Neurosci 5:917-930
241. Sandi C, Bisaz R (2007) A model for the involvement of neural cell adhesion molecules in stress-related mood disorders. Neuroen-docrinology 85(3):158-176
242. Scapagnini G, D'Agata V, Calabrese V, Pascale A, Colombrita C, Alkon D, Cavallaro S (2002) Gene expression profiles of heme oxygenase isoforms in the rat brain. Brain Res 954(1):51-59
243. Scapagnini G, Caruso C, Calabrese V (2010) Therapeutic potential of dietary polyphenols against brain ageing and neurodegenerative disorders. Adv Exp Med Biol 698:27-35
244. Scapagnini G, Caruso C, Calabrese V (2011a) Therapeutic potential of dietary polyphenols against brain ageing and neurodegener-ative disorders. Adv Exp Med Biol 698:27-35
245. Scapagnini G, Vasto S, Abraham NG, Caruso C, Zella D, Fabio G (2011b) Modulation of Nrf2/ARE pathway by food polyphenols: a nutritional neuroprotective strategy for cognitive and neuro-degenerative disorders. Mol Neurobiol 44(2):192-201
246. Schmidt HD, Duman RS (2007) The role of neurotrophic factors in adult hippocampal neurogenesis, antidepressant treatments and animal models of depressive-like behavior. Behav Pharmacol 18(5-6):391-418
247. Schmidt AJ, Heiser P, Hemmeter UM, Krieg JC, Vedder H (2008) Effects of antidepressants on mRNA levels of antioxidant enzymes in human monocytic U-937 cells. Prog Neuropsycho-pharmacol Biol Psychiatry 32(6):1567-1573
248. Seidel A, Arolt V, Hunstiger M, Rink L, Behnisch A, Kirchner H (1995) Cytokine production and serum proteins in depression. Scand J Immunol 41(6):534-538
249. Shah PJ, Glabus MF, Goodwin GM, Ebmeier KP (2002) Chronic, treatment-resistant depression and right fronto-striatal atrophy. Br J Psychiatr 180:434-440
250. Shaldubina A, Agam G, Belmaker RH (2001) The mechanism of lithium action: state of the art, ten years later. Prog Neuropsy-chopharmacol Biol Psychiatry 25(4):855-866
251. Shao L, Martin MV, Watson SJ, Schatzberg A, Akil H, Myers RM, Jones EG, Bunney WE, Vawter MP (2008) Mitochondrial involvement in psychiatric disorders. Ann Med 40(4):281-295
252. Shih AY, Johnson DA, Wong G, Kraft AD, Jiang L, Erb H, Johnson JA, Murphy TH (2003) Coordinate regulation of glutathione biosynthesis and release by Nrf2-expressing glia potently protects neurons from oxidative stress. J Neurosci 23:3394-3406
253. SirianniRW, OlaussonP,Chiu AS,Taylor JR,SaltzmanWM(2010)The behavioral and biochemical effects of BDNF containing polymers implanted in the hippocampus of rats. Brain Res 1321:40-50
254. Siwek M, Dudek D, Paul IA, Sowa-Kucma M, Zieba A, Popik P, Pilc A, Nowak G (2009) Zinc supplementation augments efficacy of imipramine in treatment resistant patients: a double blind, placebo-controlled study. J Affect Disord 118:187-195
255. Smith RAJ, Murphy MP (2011) Mitochondrial-targeted antioxidants as therapies. Disc Med 11(57):106-114
256. Smith MA, Makino S, Kvetnansky R, Post RM (1995) Stress and glucocorticoids affect the expression of brain-derived neurotro-phic factor and neurotrophin-3 mRNAs in the hippocampus. J Neurosci 15:1768-1777
257. Song C, Wang H (2011) Cytokines mediated inflammation and decreased neurogenesis in animal models of depression. Prog Neuropsychopharmacol Biol Psychiatry 35(3):760-768
258. Song C, Horrobin DF, Leonard BE (2006) The comparison of changes in behavior, neurochemistry, endocrine, and immune functions after different routes, doses and durations of administrations of IL-1beta in rats. Pharmacopsychiatry 39(3):88-99
259. Stafford L, Berk M (2011) The use of statins after a cardiac intervention is associated with reduced risk of subsequent depression: proof of concept for the inflammatory and oxidative hypotheses of depression? J Clin Psychiatry 72(9):1229-1235
260. Stambolic V, Woodgett JR (1994) Mitogen inactivation of glycogen synthase kinase-3 beta in intact cells via serine 9 phosphoryla-tion. Biochem J 303(3):701-704
261. Stavrovskaya IG, Narayanan MV, Zhang W, Krasnikov BF, Heems-kerk J, Young SS, Blass JP, Brown AM, Beal MF, Friedlander RM, Kristal BS (2004) Clinically approved heterocyclics act on a mitochondrial target and reduce stroke-induced pathology. J Exp Med 200(2):211-222
262. Stockmeier CA, Mahajan GJ, Konick LC, Overholser JC, Jurjus GJ, Meltzer HY, Uylings HB, Friedman L, Rajkowska G (2004) Cellular changes in the postmortem hippocampus in major depression. Biol Psychiatry 56(9):640-650
263. Stork C, Renshaw PF (2005) Mitochondrial dysfunction in bipolar disorder: evidence from magnetic resonance spectroscopy research. Mol Psychiatry 10(10):900-919
264. Sun Z, Zhang S, Chan JY, Zhang DD (2007) Keap1 controls postinduction repression of the Nrf2-mediated antioxidant response by escorting nuclear export of Nrf2. Mol Cell Biol 27(18):6334-6349
265. Suomalainen A, Majander A, Haltia M, Somer H, Lönnqvist J, Savontaus ML, Peltonen L (1992) Multiple deletions of mito-chondrial DNA in several tissues of a patient with severe retarded depression and familial progressive external ophthal-moplegia. J Clin Invest 90(1):61-66
266. Szewczyk B, Poleszak E, Sowa-Kucma M, Siwek M, Dudek D, Ryszewska-Pokraśniewicz B, Radziwoń-Zaleska M, Opoka W, Czekaj J, Pilc A, Nowak G (2008) Antidepressant activity of zinc and magnesium in view of current hypotheses of antidepressant action. Pharmacol Rep 60:588-599
267. Szewczyk B, Kubera M, Nowak G (2011) The role of zinc in neurodegenerative inflammatory pathways in depression. Progr Neuro Psychopharmacol Biol Psychiatry 35:693-701
268. Tsuboi H, Tatsumi A, Yamamoto K, Kobayashi F, Shimoi K, Kinae N (2006) Possible connections among job stress, depressive symptoms, lipid modulation and antioxidants. J Affect Disord 91(1):63-70
269. Turner CA, Akil H, Watson SJ, Evans SJ (2006) The fibroblast growth factor system and mood disorders. Biol Psychiatry 59(12):1128-1135
270. Ungvari Z, Sonntag WE, de Cabo R, Baur JA, Csiszar A (2011) Mitochondrial protection by resveratrol. Exerc Sport Sci Rev 39(3):128-132
271. Vaidya VA, Duman RS (2001) Depression-emerging insights from neurobiology. Br Med Bull 57:61-79
272. Valvassori SS, Rezin GT, Ferreira CL, Moretti M, Gonçalves CL, Cardoso MR, Streck EL, KapczinskiF, Quevedo J (2010) Effects of mood stabilizersonmitochondrial respiratory chain activity inbrain of rats treated with d-amphetamine. J Psychiatr Res 44(14):903-909
273. Vargas MR, Johnson DA, Sirkis DW, Messing A, Johnson JA (2008) Nrf2 activation in astrocytes protects against neurodegeneration in mouse models of familial amyotrophic lateral sclerosis. J Neurosci 50:13574-13581
274. Venugopal R, Jaiswal AK (1996) Nrf1 and Nrf2 positively and c-Fos and Fra1 negatively regulate the human antioxidant response element-mediated expression of NAD(P)H:quinone oxidoreduc-tase1 gene. Proc Natl Acad Sci USA 93(25):14960-14965
275. Wang X, Ryter SW, Dai C, Tang ZL, Watkins SC, Yin XM, Song R, Choi AM (2003) Necrotic cell death in response to oxidant stress involves the activation of the apoptogenic caspase-8/bid pathway. J Biol Chem 278(31):29184-29191
276. Wang X, Zhang J, Kim HP, Wang Y, Choi AM, Ryter SW (2004) Bcl-XL disrupts death-inducing signal complex formation in plasma membrane induced by hypoxia/reoxygenation. FASEB J 18(15):1826-1833
277. Wang D, Noda Y, Tsunekawa H, Zhou Y, Miyazaki M, Senzaki K, Nabeshima T (2007) Behavioural and neurochemical features of olfactory bulbectomized rats resembling depression with comor-bid anxiety. Behav Brain Res 178(2):262-273
278. Wang JF, Shao L, Sun X, Young LT (2009) Increased oxidative stress in the anterior cingulate cortex of subjects with bipolar disorder and schizophrenia. Bipolar Disord 11(5):523-529
279. Wang H, Brown J, Martin M (2011a) Glycogen synthase kinase 3: a point of convergence for the host inflammatory response. Cytokine 53:130-140
280. Wang X, de Rivero Vaccari JP, Wang H, Diaz P, German R, Marcillo AE, Keane RW (2011b) Activation of the nuclear factor E2-related factor 2/antioxidant response element pathway is neuroprotective after spinal cord injury. J Neurotrauma Sep 21 (Epub ahead of print)
281. Wang Y, Yang F, Liu YF, Gao F, Jiang W (2011c) Acetylsalicylic acid as an augmentation agent in fluoxetine treatment resistant depressive rats. Neurosci Lett 499(2):74-79
282. Wang Y, Xiao Z, Liu X, Berk M (2011d) Venlafaxine modulates depression-induced behaviour and the expression of Bax mRNA and Bcl-xl mRNA in both hippocampus and myocardium. Hum Psychopharmacol 26(2):95-101
283. Wei QY, Chen WF, Zhou B, Yang L, Liu ZL (2006) Inhibition of lipid peroxidation and protein oxidation in rat liver mitochondria by curcumin and its analogues. Biochim Biophys Acta 1760(1):70-77
284. Whatley SA, Curti D, Marchbanks RM (1996) Mitochondrial involvement in schizophrenia and other functional psychoses. Neurochem Res 21:995-1004
285. Whittle BJ, Varga C, Posa A, Molnar A, Collin M, Thiemermann C (2006) Reduction of experimental colitis in the rat by inhibitors of glycogen synthase kinase-3beta. Br J Pharmacol 147:575-582
286. Witte ME, Geurts JJ, de Vries HE, van der Valk P, van Horssen J (2010) Mitochondrial dysfunction: a potential link between neuroinflammation and neurodegeneration? Mitochondrion 10(5): 411-418
287. Wojda U, Salinska E, Kuznicki J (2008) Calcium ions in neuronal degeneration. IUBMB Life 60(9):575-590
288. Wrynn AS, Mac Sweeney CP, Franconi F, Lemaire L, Pouliquen D, Herlidou S, Leonard BE, Gandon J, de Certaines JD (2000) An in vivo magnetic resonance imaging study of the olfactory bulbectomized rat model of depression. Brain Res 879(1-2): 193-199
289. 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. Immuno-pharmacology 34:27-37
290. Xia ZW, Zhong WW, Xu LQ, Sun JL, Shen QX, Wang JG, Shao J, Li YZ, YuSC (2006) Heme oxygenase-1-mediated CD4?CD25high regulatory T cells suppress allergic airway inflammation. J Immunol 177(9):5936-5945
291. Xu Y, Ku BS, Yao HY, Lin YH, Ma X, Zhang YH, Li XJ (2005) Antidepressant effects of curcumin in the forced swim test and olfactory bulbectomy models of depression in rats. Pharmacol Biochem Behav 82(1):200-206
292. Xu Y, Ku B, Cui L, Li X, Barish PA, Foster TC, Ogle WO (2007) Curcumin reverses impaired hippocampal neurogenesis and increases serotonin receptor 1A mRNA and brain-derived neurotrophic factor expression in chronically stressed rats. Brain Res 1162:9-18
293. Xu Y, Wang Z, You W, Zhang X, Li S, Barish PA, Vernon MM, Du X, Li G, Pan J, Ogle WO (2010) Antidepressant-like effect of trans-resveratrol: involvement of serotonin and noradrenaline system. Eur Neuropsychopharmacol 20(6):405-413
294. Yamamoto T, Suzuki T, Kobayashi A, Wakabayashi J, Maher J, Motohashi H, Yamamoto M (2008) Physiological significance of reactive cysteine residues of Keap1 in determining Nrf2 activity. Mol Cell Biol 28(8):2758-2770
295. York JD, Ponder JW, Majerus PW (1995) Definition of a metal-dependent/Li(?)-inhibited phosphomonoesterase protein family based upon a conserved three-dimensional core structure. Proc Natl Acad Sci USA 92(11):5149-5153
296. Zafir A, Ara A, Banu N (2009) Invivo antioxidant status: a putative target of antidepressant action. Prog Neuropsychopharmacol Biol Psychiatry 33(2):220-228
297. Zhang WH, Wang H, Wang X, Narayanan MV, Stavrovskaya IG, Kristal BS, Friedlander RM (2008) Nortriptyline protects mitochondria and reduces cerebral ischemia/hypoxia injury. Stroke 39(2):455-462