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Depression and treatment response: dynamic interplay of signaling pathways and altered neural processes

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Abstract

Since the 1960s, when the first tricyclic and monoamine oxidase inhibitor antidepressant drugs were introduced, most of the ensuing agents were designed to target similar brain pathways that elevate serotonin and/or norepinephrine signaling. Fifty years later, the main goal of the current depression research is to develop faster-acting, more effective therapeutic agents with fewer side effects, as currently available antidepressants are plagued by delayed therapeutic onset and low response rates. Clinical and basic science research studies have made significant progress towards deciphering the pathophysiological events within the brain involved in development, maintenance, and treatment of major depressive disorder. Imaging and postmortem brain studies in depressed human subjects, in combination with animal behavioral models of depression, have identified a number of different cellular events, intracellular signaling pathways, proteins, and target genes that are modulated by stress and are potentially vital mediators of antidepressant action. In this review, we focus on several neural mechanisms, primarily within the hippocampus and prefrontal cortex, which have recently been implicated in depression and treatment response.

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References

  1. Kessler RC, Berglund P, Demler O, Jin R, Koretz D, Merikangas KR, Rush AJ, Walters EE, Wang PS (2003) The epidemiology of major depressive disorder: results from the National Comorbidity Survey Replication (NCS-R). JAMA 289(23):3095–3105

    Article  PubMed  Google Scholar 

  2. Greenberg PE, Kessler RC, Birnbaum HG, Leong SA, Lowe SW, Berglund PA, Corey-Lisle PK (2003) The economic burden of depression in the United States: how did it change between 1990 and 2000? J Clin Psychiatry 64(12):1465–1475

    Article  PubMed  Google Scholar 

  3. Simon GE (2003) Social and economic burden of mood disorders. Biol Psychiatry 54(3):208–215

    Article  PubMed  Google Scholar 

  4. Fava M, Davidson KG (1996) Definition and epidemiology of treatment-resistant depression. Psychiatr Clin N Am 19(2):179–200

    Article  CAS  Google Scholar 

  5. Little A (2009) Treatment-resistant depression. Am Fam Physician 80(2):167–172

    PubMed  Google Scholar 

  6. Krishnan V, Nestler EJ (2010) Linking molecules to mood: new insight into the biology of depression. Am J Psychiatry 167(11):1305–1320

    Article  PubMed  Google Scholar 

  7. 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

    Article  PubMed  Google Scholar 

  8. Sheline YI, Wang PW, Gado MH, Csernansky JG, Vannier MW (1996) Hippocampal atrophy in recurrent major depression. Proc Natl Acad Sci USA 93(9):3908–3913

    Article  PubMed  CAS  Google Scholar 

  9. Sheline YI, Gado MH, Kraemer HC (2003) Untreated depression and hippocampal volume loss. Am J Psychiatry 160(8):1516–1518

    Article  PubMed  Google Scholar 

  10. Neumeister A, Wood S, Bonne O, Nugent AC, Luckenbaugh DA, Young T, Bain EE, Charney DS, Drevets WC (2005) Reduced hippocampal volume in unmedicated, remitted patients with major depression versus control subjects. Biol Psychiatry 57(8):935–937

    Article  PubMed  Google Scholar 

  11. Campbell S, Marriott M, Nahmias C, MacQueen GM (2004) Lower hippocampal volume in patients suffering from depression: a meta-analysis. Am J Psychiatry 161(4):598–607

    Article  PubMed  Google Scholar 

  12. Videbech P, Ravnkilde B (2004) Hippocampal volume and depression: a meta-analysis of MRI studies. Am J Psychiatry 161(11):1957–1966

    Article  PubMed  Google Scholar 

  13. Bremner JD, Narayan M, Anderson ER, Staib LH, Miller HL, Charney DS (2000) Hippocampal volume reduction in major depression. Am J Psychiatry 157(1):115–118

    PubMed  CAS  Google Scholar 

  14. Cole J, Costafreda SG, McGuffin P, Fu CH (2011) Hippocampal atrophy in first episode depression: a meta-analysis of magnetic resonance imaging studies. J Affect Disord 134(1–3):483–487

    Article  PubMed  Google Scholar 

  15. Kempton MJ, Salvador Z, Munafo MR, Geddes JR, Simmons A, Frangou S, Williams SC (2011) Structural neuroimaging studies in major depressive disorder. meta-analysis and comparison with bipolar disorder. Arch Gen Psychiatry 68(7):675–690

    Article  PubMed  Google Scholar 

  16. Knable MB, Barci BM, Webster MJ, Meador-Woodruff J, Torrey EF (2004) Molecular abnormalities of the hippocampus in severe psychiatric illness: postmortem findings from the Stanley Neuropathology Consortium. Mol Psychiatry 9(6):609–620

    Google Scholar 

  17. Rajkowska G (2000) Postmortem studies in mood disorders indicate altered numbers of neurons and glial cells. Biol Psychiatry 48(8):766–777

    Article  PubMed  CAS  Google Scholar 

  18. Banasr M, Duman RS (2007) Regulation of neurogenesis and gliogenesis by stress and antidepressant treatment. CNS Neurol Disord Drug Targets 6(5):311–320

    Article  PubMed  CAS  Google Scholar 

  19. Boldrini M, Underwood MD, Hen R, Rosoklija GB, Dwork AJ, John Mann J, Arango V (2009) Antidepressants increase neural progenitor cells in the human hippocampus. Neuropsychopharmacology 34(11):2376–2389

    Article  PubMed  CAS  Google Scholar 

  20. Cotter D, Mackay D, Chana G, Beasley C, Landau S, Everall IP (2002) Reduced neuronal size and glial cell density in area 9 of the dorsolateral prefrontal cortex in subjects with major depressive disorder. Cereb Cortex 12(4):386–394

    Article  PubMed  Google Scholar 

  21. Ongur D, Drevets WC, Price JL (1998) Glial reduction in the subgenual prefrontal cortex in mood disorders. Proc Natl Acad Sci USA 95(22):13290–13295

    Article  PubMed  CAS  Google Scholar 

  22. Cotter D, Mackay D, Landau S, Kerwin R, Everall I (2001) Reduced glial cell density and neuronal size in the anterior cingulate cortex in major depressive disorder. Arch Gen Psychiatry 58(6):545–553

    Article  PubMed  CAS  Google Scholar 

  23. Rajkowska G, Miguel-Hidalgo JJ (2007) Gliogenesis and glial pathology in depression. CNS Neurol Disord Drug Targets 6(3):219–233

    Article  PubMed  CAS  Google Scholar 

  24. Miguel-Hidalgo JJ, Baucom C, Dilley G, Overholser JC, Meltzer HY, Stockmeier CA, Rajkowska G (2000) Glial fibrillary acidic protein immunoreactivity in the prefrontal cortex distinguishes younger from older adults in major depressive disorder. Biol Psychiatry 48(8):861–873

    Article  PubMed  CAS  Google Scholar 

  25. Bernard R, Kerman IA, Thompson RC, Jones EG, Bunney WE, Barchas JD, Schatzberg AF, Myers RM, Akil H, Watson SJ (2010) Altered expression of glutamate signaling, growth factor, and glia genes in the locus coeruleus of patients with major depression. Molecular Psychiatry. doi:10.1038/mp.2010.44

    PubMed  Google Scholar 

  26. Watanabe Y, Gould E, McEwen BS (1992) Stress induces atrophy of apical dendrites of hippocampal CA3 pyramidal neurons. Brain Res 588(2):341–345

    Article  PubMed  CAS  Google Scholar 

  27. Magarinos AM, Deslandes A, McEwen BS (1999) Effects of antidepressants and benzodiazepine treatments on the dendritic structure of CA3 pyramidal neurons after chronic stress. Eur J Pharmacol 371(2–3):113–122

    Article  PubMed  CAS  Google Scholar 

  28. Radley JJ, Rocher AB, Miller M, Janssen WG, Liston C, Hof PR, McEwen BS, Morrison JH (2006) Repeated stress induces dendritic spine loss in the rat medial prefrontal cortex. Cereb Cortex 16(3):313–320

    Article  PubMed  Google Scholar 

  29. Radley JJ, Morrison JH (2005) Repeated stress and structural plasticity in the brain. Ageing Res Rev 4(2):271–287

    Article  PubMed  Google Scholar 

  30. Radley JJ, Sisti HM, Hao J, Rocher AB, McCall T, Hof PR, McEwen BS, Morrison JH (2004) Chronic behavioral stress induces apical dendritic reorganization in pyramidal neurons of the medial prefrontal cortex. Neuroscience 125(1):1–6

    Article  PubMed  CAS  Google Scholar 

  31. McEwen BS, Magarinos AM, Reagan LP (2002) Structural plasticity and tianeptine: cellular and molecular targets. Eur Psychiatry 17(Suppl 3):318–330

    Article  PubMed  Google Scholar 

  32. Watanabe Y, Gould E, Daniels DC, Cameron H, McEwen BS (1992) Tianeptine attenuates stress-induced morphological changes in the hippocampus. Eur J Pharmacol 222(1):157–162

    Article  PubMed  CAS  Google Scholar 

  33. Czeh B, Michaelis T, Watanabe T, Frahm J, de Biurrun G, van Kampen M, Bartolomucci A, Fuchs E (2001) Stress-induced changes in cerebral metabolites, hippocampal volume, and cell proliferation are prevented by antidepressant treatment with tianeptine. Proc Natl Acad Sci USA 98(22):12796–12801

    Article  PubMed  CAS  Google Scholar 

  34. Malberg JE, Duman RS (2003) Cell proliferation in adult hippocampus is decreased by inescapable stress: reversal by fluoxetine treatment. Neuropsychopharmacology 28(9):1562–1571

    Article  PubMed  CAS  Google Scholar 

  35. Chen H, Pandey GN, Dwivedi Y (2006) Hippocampal cell proliferation regulation by repeated stress and antidepressants. NeuroReport 17(9):863–867

    Article  PubMed  Google Scholar 

  36. Meshi D, Drew MR, Saxe M, Ansorge MS, David D, Santarelli L, Malapani C, Moore H, Hen R (2006) Hippocampal neurogenesis is not required for behavioral effects of environmental enrichment. Nat Neurosci 9(6):729–731

    Article  PubMed  CAS  Google Scholar 

  37. Santarelli L, Saxe M, Gross C, Surget A, Battaglia F, Dulawa S, Weisstaub N, Lee J, Duman R, Arancio O, Belzung C, Hen R (2003) Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science 301(5634):805–809

    Google Scholar 

  38. Saxe MD, Battaglia F, Wang JW, Malleret G, David DJ, Monckton JE, Garcia AD, Sofroniew MV, Kandel ER, Santarelli L, Hen R, Drew MR (2006) Ablation of hippocampal neurogenesis impairs contextual fear conditioning and synaptic plasticity in the dentate gyrus. Proc Natl Acad Sci USA 103(46):17501–17506

    Article  PubMed  CAS  Google Scholar 

  39. Wei L, Meaney MJ, Duman RS, Kaffman A (2011) Affiliative behavior requires juvenile, but not adult neurogenesis. J Neurosci 31(40):14335–14345

    Article  PubMed  CAS  Google Scholar 

  40. Banasr M, Dwyer JM, Duman RS (2011) Cell atrophy and loss in depression: reversal by antidepressant treatment. Curr Opin Cell Biol 23(6):730–737

    Article  PubMed  CAS  Google Scholar 

  41. Snyder JS, Soumier A, Brewer M, Pickel J, Cameron HA (2011) Adult hippocampal neurogenesis buffers stress responses and depressive behaviour. Nature 476(7361):458–461

    Article  PubMed  CAS  Google Scholar 

  42. Duman RS, Malberg J, Nakagawa S (2001) Regulation of adult neurogenesis by psychotropic drugs and stress. J Pharmacol Exp Ther 299(2):401–407

    PubMed  CAS  Google Scholar 

  43. 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

    Article  PubMed  CAS  Google Scholar 

  44. Malberg JE, Eisch AJ, Nestler EJ, Duman RS (2000) Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci 20(24):9104–9110

    PubMed  CAS  Google Scholar 

  45. Banasr M, Valentine GW, Li XY, Gourley SL, Taylor JR, Duman RS (2007) Chronic unpredictable stress decreases cell proliferation in the cerebral cortex of the adult rat. Biol Psychiatry 62(5):496–504

    Article  PubMed  CAS  Google Scholar 

  46. Banasr M, Duman RS (2008) Glial loss in the prefrontal cortex is sufficient to induce depressive-like behaviors. Biol Psychiatry 64(10):863–870

    Article  PubMed  Google Scholar 

  47. Popoli M, Yan Z, McEwen BS, Sanacora G (2012) The stressed synapse: the impact of stress and glucocorticoids on glutamate transmission. Nat Rev 13(1):22–37

    CAS  Google Scholar 

  48. Thoenen H (1995) Neurotrophins and neuronal plasticity. Science 270(5236):593–598

    Google Scholar 

  49. Lindsay RM, Wiegand SJ, Altar CA, DiStefano PS (1994) Neurotrophic factors: from molecule to man. Trends Neurosci 17(5):182–190

    Article  PubMed  CAS  Google Scholar 

  50. Lindvall O, Kokaia Z, Bengzon J, Elmer E, Kokaia M (1994) Neurotrophins and brain insults. Trends Neurosci 17(11):490–496

    Article  PubMed  CAS  Google Scholar 

  51. Lo DC (1995) Neurotrophic factors and synaptic plasticity. Neuron 15(5):979–981

    Article  PubMed  CAS  Google Scholar 

  52. Castren E, Rantamaki T (2008) Neurotrophins in depression and antidepressant effects. Novartis Found Symp 289:43–52; discussion 53–59, 87–93

    Google Scholar 

  53. Duman RS, Heninger GR, Nestler EJ (1997) A molecular and cellular theory of depression. Arch Gen Psychiatry 54(7):597–606

    Article  PubMed  CAS  Google Scholar 

  54. Castren E, Voikar V, Rantamaki T (2007) Role of neurotrophic factors in depression. Curr Opin Pharmacol 7(1):18–21

    Article  PubMed  CAS  Google Scholar 

  55. Duman RS (2004) Role of neurotrophic factors in the etiology and treatment of mood disorders. NeuroMol Med 5(1):11–25

    Article  CAS  Google Scholar 

  56. Smith MA, Makino S, Kvetnansky R, Post RM (1995) Stress and glucocorticoids affect the expression of brain-derived neurotrophic factor and neurotrophin-3 mRNAs in the hippocampus. J Neurosci 15(3 Pt 1):1768–1777

    PubMed  CAS  Google Scholar 

  57. Rasmusson AM, Shi L, Duman R (2002) Downregulation of BDNF mRNA in the hippocampal dentate gyrus after re-exposure to cues previously associated with footshock. Neuropsychopharmacology 27(2):133–142

    Article  PubMed  CAS  Google Scholar 

  58. Nibuya M, Morinobu S, Duman RS (1995) Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments. J Neurosci 15(11):7539–7547

    PubMed  CAS  Google Scholar 

  59. Nibuya M, Nestler EJ, Duman RS (1996) Chronic antidepressant administration increases the expression of cAMP response element binding protein (CREB) in rat hippocampus. J Neurosci 16(7):2365–2372

    PubMed  CAS  Google Scholar 

  60. Russo-Neustadt A, Beard RC, Cotman CW (1999) Exercise, antidepressant medications, and enhanced brain derived neurotrophic factor expression. Neuropsychopharmacology 21(5):679–682

    Article  PubMed  CAS  Google Scholar 

  61. Russo-Neustadt AA, Beard RC, Huang YM, Cotman CW (2000) Physical activity and antidepressant treatment potentiate the expression of specific brain-derived neurotrophic factor transcripts in the rat hippocampus. Neuroscience 101(2):305–312

    Article  PubMed  CAS  Google Scholar 

  62. Allaman I, Fiumelli H, Magistretti PJ, Martin JL (2011) Fluoxetine regulates the expression of neurotrophic/growth factors and glucose metabolism in astrocytes. Psychopharmacology 216(1):75–84

    Article  PubMed  CAS  Google Scholar 

  63. Shirayama Y, Chen AC, Nakagawa S, Russell DS, Duman RS (2002) Brain-derived neurotrophic factor produces antidepressant effects in behavioral models of depression. J Neurosci 22(8):3251–3261

    PubMed  CAS  Google Scholar 

  64. Dwivedi Y, Rizavi HS, Conley RR, Roberts RC, Tamminga CA, Pandey GN (2003) Altered gene expression of brain-derived neurotrophic factor and receptor tyrosine kinase B in postmortem brain of suicide subjects. Arch Gen Psychiatry 60(8):804–815

    Article  PubMed  CAS  Google Scholar 

  65. Dwivedi Y, Mondal AC, Rizavi HS, Conley RR (2005) Suicide brain is associated with decreased expression of neurotrophins. Biol Psychiatry 58(4):315–324

    Article  PubMed  CAS  Google Scholar 

  66. Evans SJ, Choudary PV, Neal CR, Li JZ, Vawter MP, Tomita H, Lopez JF, Thompson RC, Meng F, Stead JD, Walsh DM, Myers RM, Bunney WE, Watson SJ, Jones EG, Akil H (2004) Dysregulation of the fibroblast growth factor system in major depression. Proc Natl Acad Sci USA 101(43):15506–15511

    Article  PubMed  CAS  Google Scholar 

  67. Karege F, Vaudan G, Schwald M, Perroud N, La Harpe R (2005) Neurotrophin levels in postmortem brains of suicide victims and the effects of antemortem diagnosis and psychotropic drugs. Brain Res 136(1–2):29–37

    CAS  Google Scholar 

  68. Chen B, Dowlatshahi D, MacQueen GM, Wang JF, Young LT (2001) Increased hippocampal BDNF immunoreactivity in subjects treated with antidepressant medication. Biol Psychiatry 50(4):260–265

    Article  PubMed  CAS  Google Scholar 

  69. Scharfman H, Goodman J, Macleod A, Phani S, Antonelli C, Croll S (2005) Increased neurogenesis and the ectopic granule cells after intrahippocampal BDNF infusion in adult rats. Exp Neurol 192(2):348–356

    Article  PubMed  CAS  Google Scholar 

  70. Sairanen M, Lucas G, Ernfors P, Castren M, Castren E (2005) Brain-derived neurotrophic factor and antidepressant drugs have different but coordinated effects on neuronal turnover, proliferation, and survival in the adult dentate gyrus. J Neurosci 25(5):1089–1094

    Article  PubMed  CAS  Google Scholar 

  71. D’Sa C, Duman RS (2002) Antidepressants and neuroplasticity. Bipolar Disord 4(3):183–194

    Article  PubMed  Google Scholar 

  72. Tanis KQ, Newton SS, Duman RS (2007) Targeting neurotrophic/growth factor expression and signaling for antidepressant drug development. CNS Neurol Disord Drug Targets 6(2):151–160

    Article  PubMed  CAS  Google Scholar 

  73. Dwivedi Y, Rao JS, Rizavi HS, Kotowski J, Conley RR, Roberts RC, Tamminga CA, Pandey GN (2003) Abnormal expression and functional characteristics of cyclic adenosine monophosphate response element binding protein in postmortem brain of suicide subjects. Arch Gen Psychiatry 60(3):273–282

    Article  PubMed  CAS  Google Scholar 

  74. Saarelainen T, Hendolin P, Lucas G, Koponen E, Sairanen M, MacDonald E, Agerman K, Haapasalo A, Nawa H, Aloyz R, Ernfors P, Castren E (2003) Activation of the TrkB neurotrophin receptor is induced by antidepressant drugs and is required for antidepressant-induced behavioral effects. J Neurosci 23(1):349–357

    PubMed  CAS  Google Scholar 

  75. Eisch AJ, Bolanos CA, de Wit J, Simonak RD, Pudiak CM, Barrot M, Verhaagen J, Nestler EJ (2003) Brain-derived neurotrophic factor in the ventral midbrain-nucleus accumbens pathway: a role in depression. Biol Psychiatry 54(10):994–1005

    Article  PubMed  CAS  Google Scholar 

  76. Schmidt HD, Duman RS (2010) Peripheral BDNF produces antidepressant-like effects in cellular and behavioral models. Neuropsychopharmacology 35(12):2378–2391

    Article  PubMed  CAS  Google Scholar 

  77. Hoshaw BA, Malberg JE (1037) Lucki I (2005) Central administration of IGF-I and BDNF leads to long-lasting antidepressant-like effects. Brain Res 1–2:204–208

    Google Scholar 

  78. Newton SS, Collier EF, Hunsberger J, Adams D, Terwilliger R, Selvanayagam E, Duman RS (2003) Gene profile of electroconvulsive seizures: induction of neurotrophic and angiogenic factors. J Neurosci 23(34):10841–10851

    PubMed  CAS  Google Scholar 

  79. Millauer B, Wizigmann-Voos S, Schnurch H, Martinez R, Moller NP, Risau W, Ullrich A (1993) High affinity VEGF binding and developmental expression suggest Flk-1 as a major regulator of vasculogenesis and angiogenesis. Cell 72(6):835–846

    Article  PubMed  CAS  Google Scholar 

  80. Jin K, Zhu Y, Sun Y, Mao XO, Xie L, Greenberg DA (2002) Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo. Proc Natl Acad Sci USA 99(18):11946–11950

    Article  PubMed  CAS  Google Scholar 

  81. Storkebaum E, Lambrechts D, Carmeliet P (2004) VEGF: once regarded as a specific angiogenic factor, now implicated in neuroprotection. BioEssays 26(9):943–954

    Article  PubMed  CAS  Google Scholar 

  82. Cao L, Jiao X, Zuzga DS, Liu Y, Fong DM, Young D, During MJ (2004) VEGF links hippocampal activity with neurogenesis, learning and memory. Nat Genet 36(8):827–835

    Article  PubMed  CAS  Google Scholar 

  83. Heine VM, Zareno J, Maslam S, Joels M, Lucassen PJ (2005) Chronic stress in the adult dentate gyrus reduces cell proliferation near the vasculature and VEGF and Flk-1 protein expression. Eur J Neurosci 21(5):1304–1314

    Article  PubMed  Google Scholar 

  84. Warner-Schmidt JL, Duman RS (2007) VEGF is an essential mediator of the neurogenic and behavioral actions of antidepressants. Proc Natl Acad Sci USA 104(11):4647–4652

    Article  PubMed  CAS  Google Scholar 

  85. Greene J, Banasr M, Lee B, Warner-Schmidt J, Duman RS (2009) Vascular endothelial growth factor signaling is required for the behavioral actions of antidepressant treatment: pharmacological and cellular characterization. Neuropsychopharmacology 34(11):2459–2468

    Article  PubMed  CAS  Google Scholar 

  86. Fournier NM, Duman RS (2011) Role of vascular endothelial growth factor in adult hippocampal neurogenesis: Implications for the pathophysiology and treatment of depression. Behav Brain Res. doi:10.1016/j.bbr.2011.04.022

    PubMed  Google Scholar 

  87. Thakker-Varia S, Alder J (2009) Neuropeptides in depression: role of VGF. Behav Brain Res 197(2):262–278

    Article  PubMed  CAS  Google Scholar 

  88. Malberg JE, Monteggia LM (2008) VGF, a new player in antidepressant action? Sci Signal 1(18):pe19

    Google Scholar 

  89. Hunsberger JG, Newton SS, Bennett AH, Duman CH, Russell DS, Salton SR, Duman RS (2007) Antidepressant actions of the exercise-regulated gene VGF. Nat Med 13(12):1476–1482

    Article  PubMed  CAS  Google Scholar 

  90. Thakker-Varia S, Krol JJ, Nettleton J, Bilimoria PM, Bangasser DA, Shors TJ, Black IB, Alder J (2007) The neuropeptide VGF produces antidepressant-like behavioral effects and enhances proliferation in the hippocampus. J Neurosci 27(45):12156–12167

    Article  PubMed  CAS  Google Scholar 

  91. Cattaneo A, Sesta A, Calabrese F, Nielsen G, Riva MA, Gennarelli M (2010) The expression of VGF is reduced in leukocytes of depressed patients and it is restored by effective antidepressant treatment. Neuropsychopharmacology 35(7):1423–1428

    Article  PubMed  CAS  Google Scholar 

  92. Thakker-Varia S, Jean YY, Parikh P, Sizer CF, Jernstedt Ayer J, Parikh A, Hyde TM, Buyske S, Alder J (2010) The neuropeptide VGF is reduced in human bipolar postmortem brain and contributes to some of the behavioral and molecular effects of lithium. J Neurosci 30(28):9368–9380

    PubMed  CAS  Google Scholar 

  93. Anderson MF, Aberg MA, Nilsson M, Eriksson PS (2002) Insulin-like growth factor-I and neurogenesis in the adult mammalian brain. Brain Res Dev Brain Res 134(1–2):115–122

    Article  PubMed  CAS  Google Scholar 

  94. Aberg D (2010) Role of the growth hormone/insulin-like growth factor 1 axis in neurogenesis. Endocr Dev 17:63–76

    Article  PubMed  Google Scholar 

  95. O’Kusky JR, Ye P, D’Ercole AJ (2000) Insulin-like growth factor-I promotes neurogenesis and synaptogenesis in the hippocampal dentate gyrus during postnatal development. J Neurosci 20(22):8435–8442

    PubMed  Google Scholar 

  96. Turner CA, Akil H, Watson SJ, Evans SJ (2006) The fibroblast growth factor system and mood disorders. Biol Psychiatry 59(12):1128–1135

    Article  PubMed  CAS  Google Scholar 

  97. Aberg MA, Aberg ND, Hedbacker H, Oscarsson J, Eriksson PS (2000) Peripheral infusion of IGF-I selectively induces neurogenesis in the adult rat hippocampus. J Neurosci 20(8):2896–2903

    PubMed  CAS  Google Scholar 

  98. Cheng Y, Black IB, DiCicco-Bloom E (2002) Hippocampal granule neuron production and population size are regulated by levels of bFGF. Eur J Neurosci 15(1):3–12

    Article  PubMed  Google Scholar 

  99. Aberg MA, Aberg ND, Palmer TD, Alborn AM, Carlsson-Skwirut C, Bang P, Rosengren LE, Olsson T, Gage FH, Eriksson PS (2003) IGF-I has a direct proliferative effect in adult hippocampal progenitor cells. Mol Cell Neurosci 24(1):23–40

    Article  PubMed  CAS  Google Scholar 

  100. Khawaja X, Xu J, Liang JJ, Barrett JE (2004) Proteomic analysis of protein changes developing in rat hippocampus after chronic antidepressant treatment: Implications for depressive disorders and future therapies. J Neurosci Res 75(4):451–460

    Article  PubMed  CAS  Google Scholar 

  101. Malberg JE, Platt B, Rizzo SJ, Ring RH, Lucki I, Schechter LE, Rosenzweig-Lipson S (2007) Increasing the levels of insulin-like growth factor-I by an IGF binding protein inhibitor produces anxiolytic and antidepressant-like effects. Neuropsychopharmacology 32(11):2360–2368

    Article  PubMed  CAS  Google Scholar 

  102. Trejo JL, Carro E, Torres-Aleman I (2001) Circulating insulin-like growth factor I mediates exercise-induced increases in the number of new neurons in the adult hippocampus. J Neurosci 21(5):1628–1634

    PubMed  CAS  Google Scholar 

  103. Duman CH, Schlesinger L, Terwilliger R, Russell DS, Newton SS, Duman RS (2009) Peripheral insulin-like growth factor-I produces antidepressant-like behavior and contributes to the effect of exercise. Behav Brain Res 198(2):366–371

    Article  PubMed  CAS  Google Scholar 

  104. Bachis A, Mallei A, Cruz MI, Wellstein A, Mocchetti I (2008) Chronic antidepressant treatments increase basic fibroblast growth factor and fibroblast growth factor-binding protein in neurons. Neuropharmacology 55(7):1114–1120

    Article  PubMed  CAS  Google Scholar 

  105. Gaughran F, Payne J, Sedgwick PM, Cotter D, Berry M (2006) Hippocampal FGF-2 and FGFR1 mRNA expression in major depression, schizophrenia and bipolar disorder. Brain Res Bull 70(3):221–227

    Article  PubMed  CAS  Google Scholar 

  106. Turner CA, Calvo N, Frost DO, Akil H, Watson SJ (2008) The fibroblast growth factor system is downregulated following social defeat. Neurosci Lett 430(2):147–150

    Article  PubMed  CAS  Google Scholar 

  107. Eren-Kocak E, Turner CA, Watson SJ, Akil H (2011) Short-hairpin RNA silencing of endogenous fibroblast growth factor 2 in rat hippocampus increases anxiety behavior. Biol Psychiatry 69(6):534–540

    Article  PubMed  CAS  Google Scholar 

  108. Perez JA, Clinton SM, Turner CA, Watson SJ, Akil H (2009) A new role for FGF2 as an endogenous inhibitor of anxiety. J Neurosci 29(19):6379–6387

    Article  PubMed  CAS  Google Scholar 

  109. Seth P, Koul N (2008) Astrocyte, the star avatar: redefined. J Biosci 33(3):405–421

    Article  PubMed  Google Scholar 

  110. Hisaoka K, Tsuchioka M, Yano R, Maeda N, Kajitani N, Morioka N, Nakata Y, Takebayashi M (2011) Tricyclic antidepressant amitriptyline activates fibroblast growth factor receptor signaling in glial cells: involvement in glial cell line-derived neurotrophic factor production. J Biol Chem 286(24):21118–21128

    Article  PubMed  CAS  Google Scholar 

  111. Tanis KQ, Duman RS (2007) Intracellular signaling pathways pave roads to recovery for mood disorders. Ann Med 39(7):531–544

    Article  PubMed  CAS  Google Scholar 

  112. Dwivedi Y, Rizavi HS, Roberts RC, Conley RC, Tamminga CA, Pandey GN (2001) Reduced activation and expression of ERK1/2 MAP kinase in the post-mortem brain of depressed suicide subjects. J Neurochem 77(3):916–928

    Article  PubMed  CAS  Google Scholar 

  113. Dwivedi Y, Rizavi HS, Conley RR, Pandey GN (2006) ERK MAP kinase signaling in post-mortem brain of suicide subjects: differential regulation of upstream Raf kinases Raf-1 and B-Raf. Mol Psychiatry 11(1):86–98

    Article  PubMed  CAS  Google Scholar 

  114. Hsiung SC, Adlersberg M, Arango V, Mann JJ, Tamir H, Liu KP (2003) Attenuated 5-HT1A receptor signaling in brains of suicide victims: involvement of adenylyl cyclase, phosphatidylinositol 3-kinase, Akt and mitogen-activated protein kinase. J Neurochem 87(1):182–194

    Article  PubMed  CAS  Google Scholar 

  115. Grewal SS, York RD, Stork PJ (1999) Extracellular-signal-regulated kinase signalling in neurons. Curr Opin Neurobiol 9(5):544–553

    Article  PubMed  CAS  Google Scholar 

  116. Fukunaga K, Miyamoto E (1998) Role of MAP kinase in neurons. Mol Neurobiol 16(1):79–95

    Article  PubMed  CAS  Google Scholar 

  117. Kodama M, Russell DS, Duman RS (2005) Electroconvulsive seizures increase the expression of MAP kinase phosphatases in limbic regions of rat brain. Neuropsychopharmacology 30(2):360–371

    Article  PubMed  CAS  Google Scholar 

  118. Mercier G, Lennon AM, Renouf B, Dessouroux A, Ramauge M, Courtin F, Pierre M (2004) MAP kinase activation by fluoxetine and its relation to gene expression in cultured rat astrocytes. J Mol Neurosci 24(2):207–216

    Article  PubMed  CAS  Google Scholar 

  119. Duman CH, Schlesinger L, Kodama M, Russell DS, Duman RS (2007) A role for MAP kinase signaling in behavioral models of depression and antidepressant treatment. Biol Psychiatry 61(5):661–670

    Article  PubMed  CAS  Google Scholar 

  120. Duric V, Banasr M, Licznerski P, Schmidt HD, Stockmeier CA, Simen AA, Newton SS, Duman RS (2010) A negative regulator of MAP kinase causes depressive behavior. Nat Med 16(11):1328–1332

    Article  PubMed  CAS  Google Scholar 

  121. Jeffrey KL, Camps M, Rommel C, Mackay CR (2007) Targeting dual-specificity phosphatases: manipulating MAP kinase signalling and immune responses. Nat Rev Drug Discov 6(5):391–403

    Article  PubMed  CAS  Google Scholar 

  122. Boutros T, Chevet E, Metrakos P (2008) Mitogen-activated protein (MAP) kinase/MAP kinase phosphatase regulation: roles in cell growth, death, and cancer. Pharmacol Rev 60(3):261–310

    Article  PubMed  CAS  Google Scholar 

  123. Kassel O, Sancono A, Kratzschmar J, Kreft B, Stassen M, Cato AC (2001) Glucocorticoids inhibit MAP kinase via increased expression and decreased degradation of MKP-1. EMBO J 20(24):7108–7116

    Article  PubMed  CAS  Google Scholar 

  124. Davis S, Vanhoutte P, Pages C, Caboche J, Laroche S (2000) The MAPK/ERK cascade targets both Elk-1 and cAMP response element-binding protein to control long-term potentiation-dependent gene expression in the dentate gyrus in vivo. J Neurosci 20(12):4563–4572

    PubMed  CAS  Google Scholar 

  125. Keyse SM, Emslie EA (1992) Oxidative stress and heat shock induce a human gene encoding a protein-tyrosine phosphatase. Nature 359(6396):644–647

    Article  PubMed  CAS  Google Scholar 

  126. Laderoute KR, Mendonca HL, Calaoagan JM, Knapp AM, Giaccia AJ, Stork PJ (1999) Mitogen-activated protein kinase phosphatase-1 (MKP-1) expression is induced by low oxygen conditions found in solid tumor microenvironments. A candidate MKP for the inactivation of hypoxia-inducible stress-activated protein kinase/c-Jun N-terminal protein kinase activity. J Biol Chem 274(18):12890–12897

    Article  PubMed  CAS  Google Scholar 

  127. Seta KA, Kim R, Kim HW, Millhorn DE, Beitner-Johnson D (2001) Hypoxia-induced regulation of MAPK phosphatase-1 as identified by subtractive suppression hybridization and cDNA microarray analysis. J Biol Chem 276(48):44405–44412

    Article  PubMed  CAS  Google Scholar 

  128. Liu Y, Shepherd EG, Nelin LD (2007) MAPK phosphatases—regulating the immune response. Nat Rev Immunol 7(3):202–212

    Article  PubMed  CAS  Google Scholar 

  129. Jeanneteau F, Deinhardt K (2011) Fine-tuning MAPK signaling in the brain: The role of MKP-1. Commun Integr Biol 4(3):281–283

    Article  PubMed  Google Scholar 

  130. Wu JJ, Zhang L, Bennett AM (2005) The noncatalytic amino terminus of mitogen-activated protein kinase phosphatase 1 directs nuclear targeting and serum response element transcriptional regulation. Mol Cell Biol 25(11):4792–4803

    Article  PubMed  CAS  Google Scholar 

  131. Jeanneteau F, Deinhardt K, Miyoshi G, Bennett AM, Chao MV (2010) The MAP kinase phosphatase MKP-1 regulates BDNF-induced axon branching. Nat Neurosci 13(11):1373–1379

    Article  PubMed  CAS  Google Scholar 

  132. Wu JJ, Bennett AM (2005) Essential role for mitogen-activated protein (MAP) kinase phosphatase-1 in stress-responsive MAP kinase and cell survival signaling. J Biol Chem 280(16):16461–16466

    Article  PubMed  CAS  Google Scholar 

  133. Nimah M, Zhao B, Denenberg AG, Bueno O, Molkentin J, Wong HR, Shanley TP (2005) Contribution of MKP-1 regulation of p38 to endotoxin tolerance. Shock 23 (1):80–87

    Google Scholar 

  134. Qi X, Lin W, Wang D, Pan Y, Wang W, Sun M (2009) A role for the extracellular signal-regulated kinase signal pathway in depressive-like behavior. Behav Brain Res 199(2):203–209

    Article  PubMed  CAS  Google Scholar 

  135. Einat H, Yuan P, Gould TD, Li J, Du J, Zhang L, Manji HK, Chen G (2003) The role of the extracellular signal-regulated kinase signaling pathway in mood modulation. J Neurosci 23(19):7311–7316

    PubMed  CAS  Google Scholar 

  136. Engel SR, Creson TK, Hao Y, Shen Y, Maeng S, Nekrasova T, Landreth GE, Manji HK, Chen G (2009) The extracellular signal-regulated kinase pathway contributes to the control of behavioral excitement. Mol Psychiatry 14(4):448–461

    Article  PubMed  CAS  Google Scholar 

  137. Creson TK, Hao Y, Engel S, Shen Y, Hamidi A, Zhuo M, Manji HK, Chen G (2009) The anterior cingulate ERK pathway contributes to regulation of behavioral excitement and hedonic activity. Bipolar Disord 11(4):339–350

    Article  PubMed  CAS  Google Scholar 

  138. Nusse R, Fuerer C, Ching W, Harnish K, Logan C, Zeng A, ten Berge D, Kalani Y (2008) Wnt signaling and stem cell control. Cold Spring Harb Symp Quant Biol 73:59–66

    Article  PubMed  CAS  Google Scholar 

  139. Purro SA, Ciani L, Hoyos-Flight M, Stamatakou E, Siomou E, Salinas PC (2008) Wnt regulates axon behavior through changes in microtubule growth directionality: a new role for adenomatous polyposis coli. J Neurosci 28(34):8644–8654

    Article  PubMed  CAS  Google Scholar 

  140. Ciani L, Salinas PC (2005) WNTs in the vertebrate nervous system: from patterning to neuronal connectivity. Nat Rev 6(5):351–362

    CAS  Google Scholar 

  141. Logan CY, Nusse R (2004) The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol 20:781–810

    Article  PubMed  CAS  Google Scholar 

  142. Kikuchi A, Yamamoto H, Kishida S (2007) Multiplicity of the interactions of Wnt proteins and their receptors. Cell Signal 19(4):659–671

    Article  PubMed  CAS  Google Scholar 

  143. Silva R, Mesquita AR, Bessa J, Sousa JC, Sotiropoulos I, Leao P, Almeida OF, Sousa N (2008) Lithium blocks stress-induced changes in depressive-like behavior and hippocampal cell fate: the role of glycogen-synthase-kinase-3beta. Neuroscience 152(3):656–669

    Article  PubMed  CAS  Google Scholar 

  144. Gould TD, Einat H, Bhat R, Manji HK (2004) AR-A014418, a selective GSK-3 inhibitor, produces antidepressant-like effects in the forced swim test. Int J Neuropsychopharmacol 7(4):387–390

    Article  PubMed  CAS  Google Scholar 

  145. 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

    Article  PubMed  CAS  Google Scholar 

  146. Gould TD, Manji HK (2005) Glycogen synthase kinase-3: a putative molecular target for lithium mimetic drugs. Neuropsychopharmacology 30(7):1223–1237

    PubMed  CAS  Google Scholar 

  147. Okamoto H, Voleti B, Banasr M, Sarhan M, Duric V, Girgenti MJ, Dileone RJ, Newton SS, Duman RS (2010) Wnt2 expression and signaling is increased by different classes of antidepressant treatments. Biol Psychiatry 68(6):521–527

    Article  PubMed  CAS  Google Scholar 

  148. Voleti B, Tanis KQ, Newton SS, Duman RS (2011) Analysis of target genes regulated by chronic electroconvulsive therapy reveals role for Fzd6 in depression. Biol Psychiatry. doi:10.1016/j.biopsych.2011.08.004

    PubMed  Google Scholar 

  149. Wilkinson MB, Dias C, Magida J, Mazei-Robison M, Lobo M, Kennedy P, Dietz D, Covington H 3rd, Russo S, Neve R, Ghose S, Tamminga C, Nestler EJ (2011) A novel role of the WNT-dishevelled-GSK3beta signaling cascade in the mouse nucleus accumbens in a social defeat model of depression. J Neurosci 31(25):9084–9092

    Article  PubMed  CAS  Google Scholar 

  150. Beurel E, Song L, Jope RS (2011) Inhibition of glycogen synthase kinase-3 is necessary for the rapid antidepressant effect of ketamine in mice. Molecular Psychiatry. doi:10.1038/mp.2011.47

    PubMed  Google Scholar 

  151. Holtmaat A, Svoboda K (2009) Experience-dependent structural synaptic plasticity in the mammalian brain. Nat Rev 10(9):647–658

    Article  CAS  Google Scholar 

  152. Yoshihara Y, De Roo M, Muller D (2009) Dendritic spine formation and stabilization. Curr Opin Neurobiol 19(2):146–153

    Article  PubMed  CAS  Google Scholar 

  153. Shansky RM, Hamo C, Hof PR, McEwen BS, Morrison JH (2009) Stress-induced dendritic remodeling in the prefrontal cortex is circuit specific. Cereb Cortex 19(10):2479–2484

    Article  PubMed  Google Scholar 

  154. McEwen BS (2008) Central effects of stress hormones in health and disease: Understanding the protective and damaging effects of stress and stress mediators. Eur J Pharmacol 583(2–3):174–185

    Article  PubMed  CAS  Google Scholar 

  155. Drevets WC, Ongur D, Price JL (1998) Neuroimaging abnormalities in the subgenual prefrontal cortex: implications for the pathophysiology of familial mood disorders. Mol Psychiatry 3(3):220–226, 190–221

    Google Scholar 

  156. Berman RM, Cappiello A, Anand A, Oren DA, Heninger GR, Charney DS, Krystal JH (2000) Antidepressant effects of ketamine in depressed patients. Biol Psychiatry 47(4):351–354

    Article  PubMed  CAS  Google Scholar 

  157. Zarate CA Jr, Singh JB, Carlson PJ, Brutsche NE, Ameli R, Luckenbaugh DA, Charney DS, Manji HK (2006) A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry 63(8):856–864

    Article  PubMed  CAS  Google Scholar 

  158. Li N, Lee B, Liu RJ, Banasr M, Dwyer JM, Iwata M, Li XY, Aghajanian G, Duman RS (2010) mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science 329(5994):959–964

    Google Scholar 

  159. Li N, Liu RJ, Dwyer JM, Banasr M, Lee B, Son H, Li XY, Aghajanian G, Duman RS (2011) Glutamate N-methyl-D-aspartate receptor antagonists rapidly reverse behavioral and synaptic deficits caused by chronic stress exposure. Biol Psychiatry 69(8):754–761

    Article  PubMed  CAS  Google Scholar 

  160. Duman RS, Li N, Liu RJ, Duric V, Aghajanian G (2011) Signaling pathways underlying the rapid antidepressant actions of ketamine. Neuropharmacology. doi:10.1016/j.neuropharm.2011.08.044

    PubMed  Google Scholar 

  161. Hashimoto K, Sawa A, Iyo M (2007) Increased levels of glutamate in brains from patients with mood disorders. Biol Psychiatry 62(11):1310–1316

    Article  PubMed  CAS  Google Scholar 

  162. McCullumsmith RE, Kristiansen LV, Beneyto M, Scarr E, Dean B, Meador-Woodruff JH (2007) Decreased NR1, NR2A, and SAP102 transcript expression in the hippocampus in bipolar disorder. Brain Res 1127(1):108–118

    Article  PubMed  CAS  Google Scholar 

  163. Law AJ, Deakin JF (2001) Asymmetrical reductions of hippocampal NMDAR1 glutamate receptor mRNA in the psychoses. NeuroReport 12(13):2971–2974

    Article  PubMed  CAS  Google Scholar 

  164. Nudmamud-Thanoi S, Reynolds GP (2004) The NR1 subunit of the glutamate/NMDA receptor in the superior temporal cortex in schizophrenia and affective disorders. Neurosci Lett 372(1–2):173–177

    Article  PubMed  CAS  Google Scholar 

  165. Feyissa AM, Chandran A, Stockmeier CA, Karolewicz B (2009) Reduced levels of NR2A and NR2B subunits of NMDA receptor and PSD-95 in the prefrontal cortex in major depression. Prog Neuropsychopharmacol Biol Psychiatry 33(1):70–75

    Article  PubMed  CAS  Google Scholar 

  166. Meador-Woodruff JH, Hogg AJ Jr, Smith RE (2001) Striatal ionotropic glutamate receptor expression in schizophrenia, bipolar disorder, and major depressive disorder. Brain Res Bull 55(5):631–640

    Article  PubMed  CAS  Google Scholar 

  167. Beneyto M, Meador-Woodruff JH (2006) Lamina-specific abnormalities of AMPA receptor trafficking and signaling molecule transcripts in the prefrontal cortex in schizophrenia. Synapse 60(8):585–598

    Google Scholar 

  168. Duric V, Banasr M, Stockmeier CA, Simen AA, Newton SS, Overholser JC, Jurjus GJ, Dieter L, Duman RS (2012) Altered expression of synapse and glutamate related genes in post-mortem hippocampus of depressed subjects. Int J Neuropsychopharmacol. doi:10.1017/S1461145712000016

  169. Wong ML, Smith MA, Licinio J, Doi SQ, Weiss SR, Post RM, Gold PW (1993) Differential effects of kindled and electrically induced seizures on a glutamate receptor (GluR1) gene expression. Epilepsy Res 14(3):221–227

    Article  PubMed  CAS  Google Scholar 

  170. Naylor P, Stewart CA, Wright SR, Pearson RC, Reid IC (1996) Repeated ECS induces GluR1 mRNA but not NMDAR1A-G mRNA in the rat hippocampus. Brain Res 35(1–2):349–353

    CAS  Google Scholar 

  171. Svenningsson P, Tzavara ET, Witkin JM, Fienberg AA, Nomikos GG, Greengard P (2002) Involvement of striatal and extrastriatal DARPP-32 in biochemical and behavioral effects of fluoxetine (Prozac). Proc Natl Acad Sci USA 99(5):3182–3187

    Article  PubMed  CAS  Google Scholar 

  172. Sheng M, Lee SH (2001) AMPA receptor trafficking and the control of synaptic transmission. Cell 105(7):825–828

    Article  PubMed  CAS  Google Scholar 

  173. Bruneau EG, Akaaboune M (2006) Running to stand still: ionotropic receptor dynamics at central and peripheral synapses. Mol Neurobiol 34(2):137–151

    Article  PubMed  CAS  Google Scholar 

  174. Maeng S, Zarate CA Jr, Du J, Schloesser RJ, McCammon J, Chen G, Manji HK (2008) Cellular mechanisms underlying the antidepressant effects of ketamine: role of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors. Biol Psychiatry 63(4):349–352

    Article  PubMed  CAS  Google Scholar 

  175. Autry AE, Adachi M, Nosyreva E, Na ES, Los MF, Cheng PF, Kavalali ET, Monteggia LM (2011) NMDA receptor blockade at rest triggers rapid behavioural antidepressant responses. Nature 475(7354):91–95

    Article  PubMed  CAS  Google Scholar 

  176. Homayoun H, Moghaddam B (2007) NMDA receptor hypofunction produces opposite effects on prefrontal cortex interneurons and pyramidal neurons. J Neurosci 27(43):11496–11500

    Article  PubMed  CAS  Google Scholar 

  177. Jernigan CS, Goswami DB, Austin MC, Iyo AH, Chandran A, Stockmeier CA, Karolewicz B (2011) The mTOR signaling pathway in the prefrontal cortex is compromised in major depressive disorder. Prog Neuropsychopharmacol Biol Psychiatry 35(7):1774–1779

    Article  PubMed  CAS  Google Scholar 

  178. Raison CL, Capuron L, Miller AH (2006) Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends Immunol 27(1):24–31

    Article  PubMed  CAS  Google Scholar 

  179. Miller AH, Maletic V, Raison CL (2009) Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry 65(9):732–741

    Article  PubMed  CAS  Google Scholar 

  180. Shelton RC, Claiborne J, Sidoryk-Wegrzynowicz M, Reddy R, Aschner M, Lewis DA, Mirnics K (2011) Altered expression of genes involved in inflammation and apoptosis in frontal cortex in major depression. Mol Psychiatry 16(7):751–762

    Article  PubMed  CAS  Google Scholar 

  181. 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

    Article  PubMed  CAS  Google Scholar 

  182. Koo JW, Russo SJ, Ferguson D, Nestler EJ, Duman RS (2010) Nuclear factor-kappaB is a critical mediator of stress-impaired neurogenesis and depressive behavior. Proc Natl Acad Sci USA 107(6):2669–2674

    Article  PubMed  CAS  Google Scholar 

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    Vanja Duric & Ronald S. Duman

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Duric, V., Duman, R.S. Depression and treatment response: dynamic interplay of signaling pathways and altered neural processes. Cell. Mol. Life Sci. 70, 39–53 (2013). https://doi.org/10.1007/s00018-012-1020-7

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