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