title: Neurogenic actions of atypical antipsychotic drugs and therapeutic implications.
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.
authors: Division of Molecular Psychiatry, Department of Psychiatry, Yale University School of Medicine, New Haven, Connecticut 06508, USA.
authors: Samuel S
authors: SS
authors: Newton
authors: Ronald S
authors: RS
authors: Duman
mesh_terms: D000328:Adult; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D049109:Cell Proliferation / Q000187:drug effects; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects; D003071:Cognition / Q000187:drug effects / Q000502:physiology; D006801:Humans; D009420:Nervous System / Q000187:drug effects / Q000254:growth & development* / Q000473:pathology; D011618:Psychotic Disorders / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D012559:Schizophrenia / Q000188:drug therapy / Q000473:pathology
chemical_list: D014150:Antipsychotic Agents
references: Mol Psychiatry. 2006 Sep;11(9):815-36
references: 16801952
references: Arch Gen Psychiatry. 2003 May;60(5):443-56
references: 12742865
references: Neuroreport. 2004 Sep 15;15(13):2109-12
references: 15486491
references: J Neurosci. 2005 Sep 21;25(38):8680-5
references: 16177036
references: J Neurosci. 2000 Apr 15;20(8):2896-903
references: 10751442
references: J Neurosci. 1997 Aug 1;17(15):5820-9
references: 9221780
references: J Neurosci Res. 2004 Jun 15;76(6):783-94
references: 15160390
references: Am J Psychiatry. 1994 Oct;151(10):1430-6
references: 7916539
references: J Neural Transm (Vienna). 1998;105(2-3):317-27
references: 9660110
references: Brain Res. 2005 Sep 7;1055(1-2):149-55
references: 16081054
references: FASEB J. 2002 Aug;16(10):1328-30
references: 12154010
references: J Neurosci. 2004 Aug 25;24(34):7477-81
references: 15329394
references: Br J Psychiatry. 2006 Jun;188:510-8
references: 16738340
references: Neuropsychopharmacology. 2004 Jul;29(7):1230-8
references: 15085089
references: Proc Natl Acad Sci U S A. 1999 Nov 9;96(23):13427-31
references: 10557337
references: Neuropharmacology. 1999 Jul;38(7):1075-82
references: 10428426
references: FASEB J. 2003 Feb;17 (2):186-93
references: 12554697
references: Mol Cell Neurosci. 2006 Jan;31(1):131-48
references: 16330219
references: Eur J Neurosci. 2006 Aug;24(3):661-75
references: 16930398
references: J Neural Transm (Vienna). 2004 Jan;111(1):91-100
references: 14714218
references: Neuropathol Appl Neurobiol. 1982 Mar-Apr;8(2):109-16
references: 7099384
references: Biol Psychiatry. 2000 Jun 15;47(12):1043-9
references: 10862803
references: Mol Psychiatry. 2000 Mar;5(2):142-9
references: 10822341
references: Neuroscience. 2005;136(2):381-6
references: 16216425
references: J Neurosci Res. 2002 Jul 1;69(1):72-9
references: 12111817
references: J Neurosci Res. 2005 Aug 15;81(4):572-80
references: 15948179
references: J Neurochem. 2002 Dec;83(5):1087-93
references: 12437579
references: Cereb Cortex. 2002 Apr;12(4):386-94
references: 11884354
references: Am J Psychiatry. 2002 Dec;159(12):1983-91
references: 12450946
references: Schizophr Res. 2002 Oct 1;57(2-3):127-38
references: 12223243
references: J Neurol Neurosurg Psychiatry. 1998 Oct;65(4):446-53
references: 9771764
references: Arch Gen Psychiatry. 2003 Aug;60(8):779-88
references: 12912761
references: Neurosci Lett. 2002 Mar 15;321(1-2):65-8
references: 11872258
references: Arch Gen Psychiatry. 1995 Oct;52(10):805-18; discussion 819-20
references: 7575100
references: Cell Signal. 2007 Jan;19(1):114-28
references: 16876982
references: Biol Psychiatry. 2003 Jun 15;53(12):1075-85
references: 12814859
references: Am J Psychiatry. 1994 Jun;151(6):842-8
references: 8184992
references: Eur J Neurosci. 2004 May;19(9):2377-87
references: 15128392
references: Crit Rev Neurobiol. 2000;14(1):1-21
references: 11253953
references: Schizophr Res. 2001 Apr 15;49(1-2):1-52
references: 11343862
references: Brain Res Bull. 2001 Jul 15;55(5):585-95
references: 11576755
references: Arch Gen Psychiatry. 2005 Apr;62(4):361-70
references: 15809403
references: Arch Gen Psychiatry. 2000 Aug;57(8):769-75
references: 10920465
references: Biol Psychiatry. 1999 Jul 15;46(2):161-72
references: 10418690
references: Schizophr Res. 2003 Apr 1;60(2-3):105-15
references: 12591575
references: Neuropsychopharmacology. 2001 Dec;25(6):836-44
references: 11750177
references: Am J Psychiatry. 1998 Jun;155(6):774-8
references: 9619149
references: Nat Neurosci. 2004 Jul;7(7):726-35
references: 15195095
references: Brain Res. 2004 Jun 11;1011(1):58-68
references: 15140644
references: Mol Cell Neurosci. 2002 Oct;21(2):312-23
references: 12401450
references: Science. 2003 Aug 8;301(5634):805-9
references: 12907793
references: J Neurosci. 2002 Nov 15;22(22):9868-76
references: 12427843
references: Nat Neurosci. 2006 Jun;9(6):729-31
references: 16648847
references: Brain Behav Immun. 2001 Dec;15(4):388-400
references: 11782105
references: Neuropsychopharmacology. 2004 Jun;29(6):1063-9
references: 15010699
references: J Neurosci. 2000 Jun 1;20(11):4030-6
references: 10818138
references: Arch Gen Psychiatry. 1999 Feb;56(2):133-41
references: 10025437
references: Curr Mol Med. 2003 Aug;3(5):427-36
references: 12942996
references: Biol Psychiatry. 2006 Jan 15;59(2):97-105
references: 16140282
references: Arch Gen Psychiatry. 2000 Aug;57(8):761-8
references: 10920464
references: Br J Psychiatry. 2005 Jan;186:26-31
references: 15630120
references: Neuropsychopharmacology. 2004 Mar;29(3):450-60
references: 14872203
references: Am J Psychiatry. 2000 Jan;157(1):16-25
references: 10618008
references: Neuropsychopharmacology. 2002 Aug;27(2):143-51
references: 12093588
references: Neurobiol Dis. 2005 Apr;18(3):523-7
references: 15755679
references: Schizophr Res. 2006 Sep;86(1-3):234-43
references: 16887334
references: Biol Psychiatry. 2004 Oct 15;56(8):570-80
references: 15476686
references: Psychol Med. 1993 Aug;23 (3):591-604
references: 8234567
references: Biol Psychiatry. 2003 Jul 15;54(2):111-20
references: 12873800
references: Mol Psychiatry. 2006 May;11(5):514-22
references: 16415915
references: Schizophr Bull. 2006 Apr;32(2):332-40
references: 16319377
references: J Neurochem. 2006 Sep;98 (5):1411-22
references: 16923156
references: Neuropharmacology. 2005 Dec;49(8):1178-88
references: 16143352
references: J Neurosci. 2002 May 1;22(9):3673-82
references: 11978843
references: Schizophr Res. 2002 May 1;55(1-2):1-10
references: 11955958
references: J Neurosci. 2000 Dec 15;20(24):9104-10
references: 11124987
references: Exp Brain Res. 2006 Aug;173(2):234-42
references: 16505999
references: Biol Psychiatry. 1998 Oct 15;44(8):675-84
references: 9798070
references: Am J Psychiatry. 2004 May;161(5):882-8
references: 15121654
references: J Neural Transm (Vienna). 2000;107(2):133-43
references: 10847555
references: Arch Gen Psychiatry. 1998 May;55(5):433-40
references: 9596046
references: Nat Rev Drug Discov. 2004 Apr;3(4):353-9
references: 15060530
references: Synapse. 2005 Nov;58(2):63-71
references: 16088949
references: Nature. 1997 Apr 3;386(6624):493-5
references: 9087407
references: Biol Psychiatry. 2004 Jun 1;55(11):1095-102
references: 15158429
references: J Neurosci. 1995 Nov;15(11):7539-47
references: 7472505
references: Eur J Neurosci. 1999 Nov;11(11):4006-14
references: 10583489
references: Psychiatry Res. 2005 Jul 30;139(2):127-39
references: 15967647
references: Ann N Y Acad Sci. 2004 Oct;1025:351-62
references: 15542736
references: Proc Natl Acad Sci U S A. 2005 Dec 13;102(50):18189-94
references: 16326808
references: Eur J Neurosci. 2002 Nov;16(10):2008-12
references: 12453065
references: Neuroscience. 1999;89(4):999-1002
references: 10362289
references: Am J Psychiatry. 2002 May;159(5):821-8
references: 11986137
references: J Comp Neurol. 1998 Mar 16;392(3):402-12
references: 9511926
references: Biol Psychiatry. 2004 Sep 1;56(5):301-7
references: 15336511
references: Brain Res. 2005 Nov 23;1063(1):32-9
references: 16271709
references: J Neurosci. 2005 Jun 15;25(24):5815-23
references: 15958748
references: Proc Natl Acad Sci U S A. 2000 Jun 20;97(13):7579-84
references: 10840056
references: Schizophr Res. 2005 Jun 15;75(2-3):283-94
references: 15885519
references: Proc Natl Acad Sci U S A. 2001 Apr 10;98(8):4746-51
references: 11296301
references: Proc Natl Acad Sci U S A. 2000 Sep 12;97(19):10526-31
references: 10984541
references: Proc Natl Acad Sci U S A. 2002 Sep 3;99(18):11946-50
references: 12181492
references: Mol Psychiatry. 2004 Jan;9(1):42-54
references: 14581931
references: Brain Res. 2006 Jan 27;1070(1):242-5
references: 16405875