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Neurogenic Actions of Atypical Antipsychotic Drugs and Therapeutic Implications

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Abstract

Brain imaging and postmortem studies have reported a reduction in the volume of discrete brain regions, as well as cellular abnormalities in schizophrenic patients. In addition, basic research studies have demonstrated effects of antipsychotic drugs on cell morphology and number. Of particular interest is adult neurogenesis, which has been linked to cognitive and memory improvements, and is also associated with the behavioural actions of antidepressants. While the action of antidepressant treatment is restricted mainly to the hippocampus, long-term administration of antipsychotics is reported to increase neurogenesis in the subventricular zone (SVZ), as well as the subgranular zone (SGZ) of the hippocampus. In addition, antipsychotic drugs increase the proliferation of non-neuronal cell types in the prefrontal cortex and could thereby influence the function of this brain region. Typical and atypical antipsychotic drugs differentially regulate neurogenesis in the SVZ and SGZ.

Although the therapeutic relevance remains speculative, the results are consistent with the hypothesis that the actions of antipsychotic agents could be mediated, in part, by increased proliferation of neuronal as well as glial cells. Additional animal studies and postmortem analyses are required to further test this possibility and to investigate the relevance of this work in the pathophysiology and treatment of schizophrenia.

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References

  1. Jablensky A. Subtyping schizophrenia: implications for genetic research. Mol Psychiatry 2006 Sep; 11(9): 815–36

    Article  PubMed  CAS  Google Scholar 

  2. Keshavan MS, Rosenberg D, Sweeney JA, et al. Decreased caudate volume in neuroleptic-naive psychotic patients. Am J Psychiatry 1998 Jun; 155(6): 774–8

    PubMed  CAS  Google Scholar 

  3. Velakoulis D, Pantelis C, McGorry PD, et al. Hippocampal volume in first-episode psychoses and chronic schizophrenia: a high-resolution magnetic resonance imaging study. Arch Gen Psychiatry 1999 Feb; 56(2): 133–41

    Article  PubMed  CAS  Google Scholar 

  4. Gur RE, Turetsky BI, Cowell PE, et al. Temporolimbic volume reductions in schizophrenia. Arch Gen Psychiatry 2000 Aug; 57(8): 769–75

    Article  PubMed  CAS  Google Scholar 

  5. Selemon LD, Kleinman JE, Herman MM, et al. Smaller frontal gray matter volume in postmortem schizophrenic brains. Am J Psychiatry 2002 Dec; 159(12): 1983–91

    Article  PubMed  Google Scholar 

  6. Wright IC, Rabe-Hesketh S, Woodruff PW, et al. Meta-analysis of regional brain volumes in schizophrenia. Am J Psychiatry 2000 Jan; 157(1): 16–25

    PubMed  CAS  Google Scholar 

  7. Shenton ME, Dickey CC, Frumin M, et al. A review of MRI findings in schizophrenia. Schizophr Res 2001 Apr 15; 49(1–2): 1–52

    Article  PubMed  CAS  Google Scholar 

  8. Steen RG, Mull C, McClure R, et al. Brain volume in first-episode schizophrenia: systematic review and meta-analysis of magnetic resonance imaging studies. Br J Psychiatry 2006 Jun; 188: 510–8

    Article  PubMed  Google Scholar 

  9. Sim K, DeWitt I, Ditman T, et al. Hippocampal and parahippo-campal volumes in schizophrenia: a structural MRI study. Schizophr Bull 2006 Apr; 32(2): 332–40

    Article  PubMed  Google Scholar 

  10. Harvey I, Ron MA, Du Boulay G, et al. Reduction of cortical volume in schizophrenia on magnetic resonance imaging. Psychol Med 1993 Aug; 23(3): 591–604

    Article  PubMed  CAS  Google Scholar 

  11. Schlaepfer TE, Harris GJ, Tien AY, et al. Decreased regional cortical gray matter volume in schizophrenia. Am J Psychiatry 1994 Jun; 151(6): 842–8

    PubMed  CAS  Google Scholar 

  12. Gur RE, Cowell PE, Latshaw A, et al. Reduced dorsal and orbital prefrontal gray matter volumes in schizophrenia. Arch Gen Psychiatry 2000 Aug; 57(8): 761–8

    Article  PubMed  CAS  Google Scholar 

  13. Zhou SY, Suzuki M, Hagino H, et al. Volumetric analysis of sulci/gyri-defined in vivo frontal lobe regions in schizophrenia: precentral gyrus, cingulate gyrus, and prefrontal region. Psychiatry Res 2005 Jul 30; 139(2): 127–39

    Article  PubMed  Google Scholar 

  14. Nelson MD, Saykin AJ, Flashman LA, et al. Hippocampal volume reduction in schizophrenia as assessed by magnetic resonance imaging: a meta-analytic study. Arch Gen Psychiatry 1998 May; 55(5): 433–40

    Article  PubMed  CAS  Google Scholar 

  15. Pegues MP, Rogers LJ, Amend D, et al. Anterior hippocampal volume reduction in male patients with schizophrenia. Schizophr Res 2003 Apr 1; 60(2–3): 105–15

    Article  PubMed  Google Scholar 

  16. Chakos MH, Schobel SA, Gu H, et al. Duration of illness and treatment effects on hippocampal volume in male patients with schizophrenia. Br J Psychiatry 2005 Jan; 186: 26–31

    Article  PubMed  Google Scholar 

  17. Walker MA, Highley JR, Esiri MM, et al. Estimated neuronal populations and volumes of the hippocampus and its subfields in schizophrenia. Am J Psychiatry 2002 May; 159(5): 821–8

    Article  PubMed  Google Scholar 

  18. Tanskanen P, Veijola JM, Piippo UK, et al. Hippocampus and amygdala volumes in schizophrenia and other psychoses in the Northern Finland 1966 birth cohort. Schizophr Res 2005 Jun 15; 75(2–3): 283–94

    Article  PubMed  Google Scholar 

  19. Selemon LD, Rajkowska G, Goldman-Rakic PS. Abnormally high neuronal density in the schizophrenic cortex: a morpho-metric analysis of prefrontal area 9 and occipital area 17. Arch Gen Psychiatry 1995 Oct; 52(10): 805–18; discussion 19-20

    Article  PubMed  CAS  Google Scholar 

  20. Selemon LD, Rajkowska G, Goldman-Rakic PS. Elevated neuronal density in prefrontal area 46 in brains from schizophrenic patients: application of a three-dimensional, stereologic counting method. J Comp Neurol 1998 Mar 16; 392(3): 402–12

    Article  PubMed  CAS  Google Scholar 

  21. Pierri JN, Volk CL, Auh S, et al. Somal size of prefrontal cortical pyramidal neurons in schizophrenia: differential effects across neuronal subpopulations. Biol Psychiatry 2003 Jul 15; 54(2): 111–20

    Article  PubMed  Google Scholar 

  22. Selemon LD, Rajkowska G. Cellular pathology in the dorso-lateral prefrontal cortex distinguishes schizophrenia from bipolar disorder. Curr Mol Med 2003 Aug; 3(5): 427–36

    Article  PubMed  CAS  Google Scholar 

  23. Garey LJ, Ong WY, Patel TS, et al. Reduced dendritic spine density on cerebral cortical pyramidal neurons in schizophrenia. J Neurol Neurosurg Psychiatry 1998 Oct; 65(4): 446–53

    Article  PubMed  CAS  Google Scholar 

  24. Garey LJ, Von Bussmann KA, Hirsch SR. Decreased numerical density of kainate receptor-positive neurons in the orbitofrontal cortex of chronic schizophrenics. Exp Brain Res 2006 Aug; 173(2): 234–42

    Article  PubMed  CAS  Google Scholar 

  25. Zhang ZJ, Reynolds GP. A selective decrease in the relative density of parvalbumin-immunoreactive neurons in the hippocampus in schizophrenia. Schizophr Res 2002 May 1; 55(1–2): 1–10

    Article  PubMed  Google Scholar 

  26. Reif A, Fritzen S, Finger M, et al. Neural stem cell proliferation is decreased in schizophrenia, but not in depression. Mol Psychiatry 2006 May; 11(5): 514–22

    Article  PubMed  CAS  Google Scholar 

  27. Rajkowska G, Miguel-Hidalgo JJ, Makkos Z, et al. Layer-specific reductions in GFAP-reactive astroglia in the dorso-lateral prefrontal cortex in schizophrenia. Schizophr Res 2002 Oct 1; 57(2–3): 127–38

    Article  PubMed  Google Scholar 

  28. Hof PR, Haroutunian V, Friedrich Jr VL, et al. Loss and altered spatial distribution of oligodendrocytes in the superior frontal gyrus in schizophrenia. Biol Psychiatry 2003 Jun 15; 53(12): 1075–85

    Article  PubMed  CAS  Google Scholar 

  29. Hakak Y, Walker JR, Li C, et al. Genome-wide expression analysis reveals dysregulation of myelination-related genes in chronic schizophrenia. Proc Natl Acad Sci U S A 2001 Apr 10; 98(8): 4746–51

    Article  PubMed  CAS  Google Scholar 

  30. Cotter D, Mackay D, Chana G, et al. Reduced neuronal size and glial cell density in area 9 of the dorsolateral prefrontal cortex in subjects with major depressive disorder. Cereb Cortex 2002 Apr; 12(4): 386–94

    Article  PubMed  Google Scholar 

  31. Stark AK, Uylings HB, Sanz-Arigita E, et al. Glial cell loss in the anterior cingulate cortex, a subregion of the prefrontal cortex, in subjects with schizophrenia. Am J Psychiatry 2004 May; 161(5): 882–8

    Article  PubMed  Google Scholar 

  32. Johnston-Wilson NL, Sims CD, Hofmann JP, et al. Disease-specific alterations in frontal cortex brain proteins in schizophrenia, bipolar disorder, and major depressive disorder. The Stanley Neuropathology Consortium. Mol Psychiatry 2000 Mar; 5(2): 142–9

    CAS  Google Scholar 

  33. Kempermann G, Kuhn HG, Gage FH. More hippocampal neurons in adult mice living in an enriched environment. Nature 1997 Apr 3; 386(6624): 493–5

    Article  PubMed  CAS  Google Scholar 

  34. Madsen TM, Treschow A, Bengzon J, et al. Increased neurogenesis in a model of electroconvulsive therapy. Biol Psychiatry 2000 Jun 15; 47(12): 1043–9

    Article  PubMed  CAS  Google Scholar 

  35. Malberg JE, Eisch AJ, Nestler EJ, et al. Chronic antidepressant treatment increases neurogenesis in adult rat hippocampus. J Neurosci 2000 Dec 15; 20(24): 9104–10

    PubMed  CAS  Google Scholar 

  36. Duman RS, Nakagawa S, Malberg J. Regulation of adult neurogenesis by antidepressant treatment. Neuropsychopharmacology 2001 Dec; 25(6): 836–44

    Article  PubMed  CAS  Google Scholar 

  37. van Praag H, Shubert T, Zhao C, et al. Exercise enhances learning and hippocampal neurogenesis in aged mice. J Neurosci 2005 Sep 21; 25(38): 8680–5

    Article  PubMed  CAS  Google Scholar 

  38. Nixon K, Crews FT. Binge ethanol exposure decreases neurogenesis in adult rat hippocampus. J Neurochem 2002 Dec; 83(5): 1087–93

    Article  PubMed  CAS  Google Scholar 

  39. Eisch AJ, Barrot M, Schad CA, et al. Opiates inhibit neurogenesis in the adult rat hippocampus. Proc Natl Acad Sci U S A 2000 Jun 20; 97(13): 7579–84

    Article  PubMed  CAS  Google Scholar 

  40. Teuchert-Noodt G, Dawirs RR, Hildebrandt K. Adult treatment with methamphetamine transiently decreases dentate granule cell proliferation in the gerbil hippocampus. J Neural Transm 2000; 107(2): 133–43

    Article  PubMed  CAS  Google Scholar 

  41. Yamaguchi M, Suzuki T, Seki T, et al. Repetitive cocaine administration decreases neurogenesis in adult rat hippocampus. Ann N Y Acad Sci 2004 Oct; 1025: 351–62

    Article  PubMed  CAS  Google Scholar 

  42. Yamaguchi M, Suzuki T, Seki T, et al. Decreased cell proliferation in the dentate gyrus of rats after repeated administration of cocaine. Synapse 2005 Nov; 58(2): 63–71

    Article  PubMed  CAS  Google Scholar 

  43. Mandyam CD, Norris RD, Eisch AJ. Chronic morphine induces premature mitosis of proliferating cells in the adult mouse subgranular zone. J Neurosci Res 2004 Jun 15; 76(6): 783–94

    Article  PubMed  CAS  Google Scholar 

  44. Mackowiak M, Markowicz-Kula K, Fijal K, et al. Acute and repeated administration of cocaine differentially regulates expression of PSA-NCAM-positive neurons in the rat hippocampus. Brain Res 2005 Sep 7; 1055(1–2): 149–55

    Article  PubMed  CAS  Google Scholar 

  45. Santarelli L, Saxe M, Gross C, et al. Requirement of hippocampal neurogenesis for the behavioral effects of antidepressants. Science 2003 Aug 8; 301(5634): 805–9

    Article  PubMed  CAS  Google Scholar 

  46. Brezun JM, Daszuta A. Depletion in serotonin decreases neurogenesis in the dentate gyrus and the subventricular zone of adult rats. Neuroscience 1999; 89(4): 999–1002

    Article  PubMed  CAS  Google Scholar 

  47. Hoglinger GU, Rizk P, Muriel MP, et al. Dopamine depletion impairs precursor cell proliferation in Parkinson disease. Nat Neurosci 2004 Jul; 7(7): 726–35

    Article  PubMed  CAS  Google Scholar 

  48. Van Kampen JM, Hagg T, Robertson HA. Induction of neurogenesis in the adult rat subventricular zone and neostriatum following dopamine D receptor stimulation. Eur J Neurosci 2004 May; 19(9): 2377–87

    Article  PubMed  Google Scholar 

  49. Kippin TE, Kapur S, van der Kooy D. Dopamine specifically inhibits forebrain neural stem cell proliferation, suggesting a novel effect of antipsychotic drugs. J Neurosci 2005 Jun 15; 25(24): 5815–23

    Article  PubMed  CAS  Google Scholar 

  50. Baker SA, Baker KA, Hagg T. D3 dopamine receptors do not regulate neurogenesis in the subventricular zone of adult mice. Neurobiol Dis 2005 Apr; 18(3): 523–7

    Article  PubMed  CAS  Google Scholar 

  51. Banasr M, Hery M, Printemps R, et al. Serotonin-induced increases in adult cell proliferation and neurogenesis are mediated through different and common 5-HT receptor subtypes in the dentate gyrus and the subventricular zone. Neuropsychopharmacology 2004 Mar; 29(3): 450–60

    Article  PubMed  CAS  Google Scholar 

  52. Kodama M, Fujioka T, Duman RS. Chronic olanzapine or fluoxetine administration increases cell proliferation in hippocampus and prefrontal cortex of adult rat. Biol Psychiatry 2004 Oct 15; 56(8): 570–80

    Article  PubMed  CAS  Google Scholar 

  53. Wang HD, Dunnavant FD, Jarman T, et al. Effects of antipsychotic drugs on neurogenesis in the forebrain of the adult rat. Neuropsychopharmacology 2004 Jul; 29(7): 1230–8

    Article  PubMed  CAS  Google Scholar 

  54. Halim ND, Weickert CS, McClintock BW, et al. Effects of chronic haloperidol and clozapine treatment on neurogenesis in the adult rat hippocampus. Neuropsychopharmacology 2004 Jun; 29(6): 1063–9

    Article  PubMed  CAS  Google Scholar 

  55. Wakade CG, Mahadik SP, Waller JL, et al. Atypical neuroleptics stimulate neurogenesis in adult rat brain. J Neurosci Res 2002 Jul 1; 69(1): 72–9

    Article  PubMed  CAS  Google Scholar 

  56. Green W, Patil P, Marsden CA, et al. Treatment with olanzapine increases cell proliferation in the subventricular zone and prefrontal cortex. Brain Res 2006 Jan 27; 1070(1): 242–5

    Article  PubMed  CAS  Google Scholar 

  57. Schmitt A, Weber S, Jatzko A, et al. Hippocampal volume and cell proliferation after acute and chronic clozapine or haloperidol treatment. J Neural Transm 2004 Jan; 111(1): 91–100

    Article  PubMed  CAS  Google Scholar 

  58. Dawirs RR, Hildebrandt K, Teuchert-Noodt G. Adult treatment with haloperidol increases dentate granule cell proliferation in the gerbil hippocampus. J Neural Transm 1998; 105(2–3): 317–27

    Article  PubMed  CAS  Google Scholar 

  59. Backhouse B, Barochovsky O, Malik C, et al. Effects of haloperidol on cell proliferation in the early postnatal rat brain. Neuropathol Appl Neurobiol 1982 Mar–Apr; 8(2): 109–16

    Article  PubMed  CAS  Google Scholar 

  60. Luo C, Xu H, Li XM. Quetiapine reverses the suppression of hippocampal neurogenesis caused by repeated restraint stress. Brain Res 2005 Nov 23; 1063(1): 32–9

    Article  PubMed  CAS  Google Scholar 

  61. Xu H, Qing H, Lu W, et al. Quetiapine attenuates the immobilization stress-induced decrease of brain-derived neurotrophic factor expression in rat hippocampus. Neurosci Lett 2002 Mar 15; 321(1–2): 65–8

    Article  PubMed  CAS  Google Scholar 

  62. Wang H, Xu H, Dyck LE, et al. Olanzapine and quetiapine protect PC12 cells from beta-amyloid peptide(25–35)-induced oxidative stress and the ensuing apoptosis. J Neurosci Res 2005 Aug 15; 81(4): 572–80

    Article  PubMed  CAS  Google Scholar 

  63. Lu XH, Bradley RJ, Dwyer DS. Olanzapine produces trophic effects in vitro and stimulates phosphorylation of Akt/PKB, ERK1/2, and the mitogen-activated protein kinase p 38. Brain Res 2004 Jun 11; 1011(1): 58–68

    Article  PubMed  CAS  Google Scholar 

  64. Pillai A, Mahadik SP. Differential effects of haloperidol and olanzapine on the expression of erythropoietin and its receptor in rat hippocampus and striatum. J Neurochem 2006 Sep; 98(5): 1411–22

    Article  PubMed  CAS  Google Scholar 

  65. Brines ML, Ghezzi P, Keenan S, et al. Erythropoietin crosses the blood-brain barrier to protect against experimental brain injury. Proc Natl Acad Sci U S A 2000 Sep 12; 97(19): 10526–31

    Article  PubMed  CAS  Google Scholar 

  66. Ehrenreich H, Degner D, Meller J, et al. Erythropoietin: a candidate compound for neuroprotection in schizophrenia. Mol Psychiatry 2004 Jan; 9(1): 42–54

    PubMed  CAS  Google Scholar 

  67. Selemon LD, Lidow MS, Goldman-Rakic PS. Increased volume and glial density in primate prefrontal cortex associated with chronic antipsychotic drug exposure. Biol Psychiatry 1999 Jul 15; 46(2): 161–72

    Article  PubMed  CAS  Google Scholar 

  68. Webster MJ, Knable MB, Johnston-Wilson N, et al. Immunohistochemical localization of phosphorylated glial fibrillary acidic protein in the prefrontal cortex and hippocampus from patients with schizophrenia, bipolar disorder, and depression. Brain Behav Immun 2001 Dec; 15(4): 388–400

    Article  PubMed  CAS  Google Scholar 

  69. Cotter DR, Pariante CM, Everall IP. Glial cell abnormalities in major psychiatric disorders: the evidence and implications. Brain Res Bull 2001 Jul 15; 55(5): 585–95

    Article  PubMed  CAS  Google Scholar 

  70. Jin K, Zhu Y, Sun Y, et al. Vascular endothelial growth factor (VEGF) stimulates neurogenesis in vitro and in vivo. Proc Natl Acad Sci U S A 2002 Sep 3; 99(18): 11946–50

    Article  PubMed  CAS  Google Scholar 

  71. Cooper-Kuhn CM, Vroemen M, Brown J, et al. Impaired adult neurogenesis in mice lacking the transcription factor E2F 1. Mol Cell Neurosci 2002 Oct; 21(2): 312–23

    Article  PubMed  CAS  Google Scholar 

  72. Zhu Y, Jin K, Mao XO, et al. Vascular endothelial growth factor promotes proliferation of cortical neuron precursors by regulating E2F expression. Faseb J 2003 Feb; 17(2): 186–93

    Article  PubMed  CAS  Google Scholar 

  73. Aberg MA, Aberg ND, Hedbacker H, et al. Peripheral infusion of IGF-I selectively induces neurogenesis in the adult rat hippocampus. J Neurosci 2000 Apr 15; 20(8): 2896–903

    PubMed  CAS  Google Scholar 

  74. Jin K, LaFevre-Bernt M, Sun Y, et al. FGF-2 promotes neurogenesis and neuroprotection and prolongs survival in a transgenic mouse model of Huntington’s disease. Proc Natl Acad Sci U S A 2005 Dec 13; 102(50): 18189–94

    Article  PubMed  CAS  Google Scholar 

  75. Katoh-Semba R, Asano T, Ueda H, et al. Riluzole enhances expression of brain-derived neurotrophic factor with consequent proliferation of granule precursor cells in the rat hippocampus. Faseb J 2002 Aug; 16(10): 1328–30

    PubMed  CAS  Google Scholar 

  76. Kuhn HG, Winkler J, Kempermann G, et al. Epidermal growth factor and fibroblast growth factor-2 have different effects on neural progenitors in the adult rat brain. J Neurosci 1997 Aug 1; 17(15): 5820–9

    PubMed  CAS  Google Scholar 

  77. Nakagawa S, Kim JE, Lee R, et al. Localization of phosphorylated cAMP response element-binding protein in immature neurons of adult hippocampus. J Neurosci 2002 Nov 15; 22(22): 9868–76

    PubMed  CAS  Google Scholar 

  78. Thome J, Sakai N, Shin K, et al. cAMP response element-mediated gene transcription is upregulated by chronic antidepressant treatment. J Neurosci 2000 Jun 1; 20(11): 4030–6

    PubMed  CAS  Google Scholar 

  79. Nakagawa S, Kim JE, Lee R, et al. Regulation of neurogenesis in adult mouse hippocampus by cAMP and the cAMP response element-binding protein. J Neurosci 2002 May 1; 22(9): 3673–82

    PubMed  CAS  Google Scholar 

  80. Lim DA, Suarez-Farinas M, Naef F, et al. In vivo transcriptional profile analysis reveals RNA splicing and chromatin remodeling as prominent processes for adult neurogenesis. Mol Cell Neurosci 2006 Jan; 31(1): 131–48

    Article  PubMed  CAS  Google Scholar 

  81. Bonnert TP, Bilsland JG, Guest PC, et al. Molecular characterization of adult mouse subventricular zone progenitor cells during the onset of differentiation. Eur J Neurosci 2006 Aug; 24(3): 661–75

    Article  PubMed  Google Scholar 

  82. Nibuya M, Morinobu S, Duman RS. Regulation of BDNF and trkB mRNA in rat brain by chronic electroconvulsive seizure and antidepressant drug treatments. J Neurosci 1995 Nov; 15(11): 7539–47

    PubMed  CAS  Google Scholar 

  83. Maragnoli ME, Fumagalli F, Gennarelli M, et al. Fluoxetine and olanzapine have synergistic effects in the modulation of fibroblast growth factor 2 expression within the rat brain. Biol Psychiatry 2004 Jun 1; 55(11): 1095–102

    Article  PubMed  CAS  Google Scholar 

  84. Chen MJ, Nguyen TV, Pike CJ, et al. Norepinephrine induces BDNF and activates the PI-3K and MAPK cascades in embryonic hippocampal neurons. Cell Signal 2007 Jan; 19(1): 114–28

    Article  PubMed  CAS  Google Scholar 

  85. Martinez-Turrillas R, Del Rio J, Frechilla D. Sequential changes in BDNF mRNA expression and synaptic levels of AMPA receptor subunits in rat hippocampus after chronic antidepressant treatment. Neuropharmacology 2005 Dec; 49(8): 1178–88

    Article  PubMed  CAS  Google Scholar 

  86. Fumagalli F, Molteni R, Bedogni F, et al. Quetiapine regulates FGF-2 and BDNF expression in the hippocampus of animals treated with MK-801. Neuroreport 2004 Sep 15; 15(13): 2109–12

    Article  PubMed  CAS  Google Scholar 

  87. Riva MA, Molteni R, Tascedda F, et al. Selective modulation of fibroblast growth factor-2 expression in the rat brain by the atypical antipsychotic clozapine. Neuropharmacology 1999 Jul; 38(7): 1075–82

    Article  PubMed  CAS  Google Scholar 

  88. Kulkarni VA, Jha S, Vaidya VA. Depletion of norepinephrine decreases the proliferation, but does not influence the survival and differentiation, of granule cell progenitors in the adult rat hippocampus. Eur J Neurosci 2002 Nov; 16(10): 2008–12

    Article  PubMed  Google Scholar 

  89. Roth BL, Sheffler DJ, Kroeze WK. Magic shotguns versus magic bullets: selectively non-selective drugs for mood disorders and schizophrenia. Nat Rev Drug Discov 2004 Apr; 3(4): 353–9

    Article  PubMed  CAS  Google Scholar 

  90. Andersson C, Hamer RM, Lawler CP, et al. Striatal volume changes in the rat following long-term administration of typical and atypical antipsychotic drugs. Neuropsychopharmacology 2002 Aug; 27(2): 143–51

    Article  PubMed  CAS  Google Scholar 

  91. Van Kampen JM, Robertson HA. A possible role for dopamine D3 receptor stimulation in the induction of neurogenesis in the adult rat substantia nigra. Neuroscience 2005; 136(2): 381–6

    Article  PubMed  CAS  Google Scholar 

  92. Bagary MS, Symms MR, Barker GJ, et al. Gray and white matter brain abnormalities in first-episode schizophrenia inferred from magnetization transfer imaging. Arch Gen Psychiatry 2003 Aug; 60(8): 779–88

    Article  PubMed  Google Scholar 

  93. Davis KL, Stewart DG, Friedman JI, et al. White matter changes in schizophrenia: evidence for myelin-related dysfunction. Arch Gen Psychiatry 2003 May; 60(5): 443–56

    Article  PubMed  Google Scholar 

  94. Chakos MH, Lieberman JA, Bilder RM, et al. Increase in caudate nuclei volumes of first-episode schizophrenic patients taking antipsychotic drugs. Am J Psychiatry 1994 Oct; 151(10): 1430–6

    PubMed  CAS  Google Scholar 

  95. Chakos MH, Shirakawa O, Lieberman J, et al. Striatal enlargement in rats chronically treated with neuroleptic. Biol Psychiatry 1998 Oct 15; 44(8): 675–84

    Article  PubMed  CAS  Google Scholar 

  96. Lieberman JA, Tollefson GD, Charles C, et al. Antipsychotic drug effects on brain morphology in first-episode psychosis. Arch Gen Psychiatry 2005 Apr; 62(4): 361–70

    Article  PubMed  CAS  Google Scholar 

  97. Green AI, Lieberman JA, Hamer RM, et al. Olanzapine and haloperidol in first episode psychosis: two-year data. Schizophr Res 2006 Sep; 86(1–3): 234–43

    Article  PubMed  CAS  Google Scholar 

  98. Keefe RS, Seidman LJ, Christensen BK, et al. Long-term neurocognitive effects of olanzapine or low-dose haloperidol in first-episode psychosis. Biol Psychiatry 2006 Jan 15; 59(2): 97–105

    Article  PubMed  CAS  Google Scholar 

  99. Elvevag B, Goldberg TE. Cognitive impairment in schizophrenia is the core of the disorder. Crit Rev Neurobiol 2000; 14(1): 1–21

    Article  PubMed  CAS  Google Scholar 

  100. Green MF, Nuechterlein KH, Gold JM, et al. Approaching a consensus cognitive battery for clinical trials in schizophrenia: the NIMH-MATRICS conference to select cognitive domains and test criteria. Biol Psychiatry 2004 Sep 1; 56(5): 301–7

    Article  PubMed  Google Scholar 

  101. van Praag H, Christie BR, Sejnowski TJ, et al. Running enhances neurogenesis, learning, and long-term potentiation in mice. Proc Natl Acad Sci U S A 1999 Nov 9; 96(23): 13427–31

    Article  PubMed  Google Scholar 

  102. Lemaire V, Aurousseau C, Le Moal M, et al. Behavioural trait of reactivity to novelty is related to hippocampal neurogenesis. Eur J Neurosci 1999 Nov; 11(11): 4006–14

    Article  PubMed  CAS  Google Scholar 

  103. Leuner B, Mendolia-Loffredo S, Kozorovitskiy Y, et al. Learning enhances the survival of new neurons beyond the time when the hippocampus is required for memory. J Neurosci 2004 Aug 25; 24(34): 7477–81

    Article  PubMed  CAS  Google Scholar 

  104. Meshi D, Drew MR, Saxe M, et al. Hippocampal neurogenesis is not required for behavioral effects of environmental enrichment. Nat Neurosci 2006 Jun; 9(6): 729–31

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This work was supported by USPHS grants MH45481, 2 PO1 MH25642, U24 NS051869, a Veterans Administration National Center Grant for PTSD, and by the Connecticut Mental Health Center.

Ronald Duman has previously acted as a consultant for Taisho Pharmaceutical and Wyeth-Ayerst, and has received honoraria for speaking from Eli Lilly and Bristol-Myers Squibb. He has also received grants from Eli Lilly, Organon and Sepracor. Samuel Newton has no conflicts of interest that are directly relevant to the content of this review.

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  1. S-308, Division of Molecular Psychiatry, Departments of Psychiatry and Pharmacology, Yale University School of Medicine, CMHC, 34 Park Street, New Haven, Connecticut, 06508, USA

    Samuel S. Newton &  Ronald S. Duman

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Newton, S.S., Duman, R.S. Neurogenic Actions of Atypical Antipsychotic Drugs and Therapeutic Implications. CNS Drugs 21, 715–725 (2007). https://doi.org/10.2165/00023210-200721090-00002

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