title: Insights into the neurodevelopmental origin of schizophrenia from postmortem studies of prefrontal cortical circuitry.
abstract: The hypothesis that schizophrenia results from a developmental, as opposed to a degenerative, process affecting the connectivity and network plasticity of the cerebral cortex is supported by findings from morphological and molecular postmortem studies. Specifically, abnormalities in the expression of protein markers of GABA neurotransmission and the lamina- and circuit-specificity of these changes in the cortex in schizophrenia, in concert with knowledge of their developmental trajectories, offer crucial insight into the vulnerability of specific cortical networks to environmental insults during different periods of development. These findings reveal potential targets for therapeutic interventions to improve cognitive function in individuals with schizophrenia, and provide guidance for future preventive strategies to preserve cortical neurotransmission in at-risk individuals.
authors.affiliation: Department of Psychiatry, University of Pittsburgh, W1656 Biomedical Science Tower, 3811 O'Hara Street, Pittsburgh, PA 15213, USA. beneytom@upmc.edu
authors.forename: Monica
authors.initials: M
authors.lastname: Beneyto
authors.forename: David A
authors.initials: DA
authors.lastname: Lewis
mesh_terms: D001344:Autopsy; D015415:Biomarkers / Q000378:metabolism; D006801:Humans; D009415:Nerve Net / Q000033:anatomy & histology / Q000473:pathology* / Q000502:physiology / Q000503:physiopathology*; D017397:Prefrontal Cortex / Q000033:anatomy & histology* / Q000254:growth & development* / Q000503:physiopathology; D021122:Protein Subunits / Q000378:metabolism; D011963:Receptors, GABA-A / Q000378:metabolism; D012559:Schizophrenia / Q000473:pathology* / Q000503:physiopathology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D015415:Biomarkers; D021122:Protein Subunits; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid
references.citation: J Neurosci. 2001 Jun 1;21(11):3788-96
references.pmid: 11356867
references.citation: Neuroscience. 1999;93(2):441-8
references.pmid: 10465426
references.citation: J Neurosci. 2003 Nov 26;23(34):10934-43
references.pmid: 14645489
references.citation: J Histochem Cytochem. 1998 Oct;46(10):1129-39
references.pmid: 9742069
references.citation: Cereb Cortex. 2005 Aug;15(8):1178-86
references.pmid: 15590911
references.citation: Science. 1986 Apr 11;232(4747):232-5
references.pmid: 3952506
references.citation: Am J Psychiatry. 2008 Apr;165(4):479-89
references.pmid: 18281411
references.citation: Neuroscience. 2007 Feb 9;144(3):1109-19
references.pmid: 17123740
references.citation: Arch Gen Psychiatry. 1987 Jul;44(7):660-9
references.pmid: 3606332
references.citation: J Comp Neurol. 1993 Oct 15;336(3):400-18
references.pmid: 8263229
references.citation: J Biol Chem. 1993 Mar 15;268(8):5965-73
references.pmid: 8383681
references.citation: J Neurosci. 2005 Jan 12;25(2):372-83
references.pmid: 15647480
references.citation: J Comp Neurol. 1997 Oct 20;387(2):167-78
references.pmid: 9336221
references.citation: Trends Neurosci. 2007 Jul;30(7):317-24
references.pmid: 17499860
references.citation: Child Dev. 2004 Sep-Oct;75(5):1357-72
references.pmid: 15369519
references.citation: J Chem Neuroanat. 1997 Dec;14(1):1-19
references.pmid: 9498163
references.citation: Cereb Cortex. 2010 May;20(5):1164-74
references.pmid: 19703937
references.citation: J Neurosci. 2003 Jul 16;23(15):6315-26
references.pmid: 12867516
references.citation: Biol Psychiatry. 2009 Jun 15;65(12):1015-23
references.pmid: 19249749
references.citation: J Neurophysiol. 1993 Jul;70(1):387-96
references.pmid: 8395585
references.citation: Nat Rev Neurosci. 2007 Jan;8(1):45-56
references.pmid: 17180162
references.citation: Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):5341-6
references.pmid: 9560277
references.citation: J Comp Neurol. 1993 Jan 15;327(3):398-415
references.pmid: 8440773
references.citation: J Comp Neurol. 1990 Nov 1;301(1):123-37
references.pmid: 1706355
references.citation: J Neurophysiol. 2005 Nov;94(5):3009-22
references.pmid: 15987765
references.citation: J Psychiatry Neurosci. 2009 Nov;34(6):450-8
references.pmid: 19949721
references.citation: Exp Brain Res. 1989;75(3):457-69
references.pmid: 2744104
references.citation: Neuropsychopharmacology. 2009 Aug;34(9):2112-24
references.pmid: 19322171
references.citation: Mol Psychiatry. 2008 Feb;13(2):147-61
references.pmid: 17471287
references.citation: J Comp Neurol. 1996 Jan 22;364(4):609-36
references.pmid: 8821450
references.citation: Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11939-44
references.pmid: 8876241
references.citation: Experientia. 1984 Sep 15;40(9):910-21
references.pmid: 6205895
references.citation: Hum Neurobiol. 1987;6(1):1-9
references.pmid: 3583840
references.citation: Adv Neurol. 1992;57:91-115
references.pmid: 1543090
references.citation: Mol Psychiatry. 2007 Sep;12(9):854-69
references.pmid: 17767149
references.citation: Am J Psychiatry. 2009 Apr;166(4):450-9
references.pmid: 19289452
references.citation: J Neurosci. 2002 Apr 1;22(7):2513-21
references.pmid: 11923416
references.citation: Proc Natl Acad Sci U S A. 2006 Jun 13;103(24):9315-20
references.pmid: 16738055
references.citation: J Comp Neurol. 1993 Dec 15;338(3):360-76
references.pmid: 8113445
references.citation: Neuron. 2007 Mar 15;53(6):805-12
references.pmid: 17359916
references.citation: Brain Res. 1979 Mar 16;163(2):195-205
references.pmid: 427544
references.citation: Neuroscience. 2007 Mar 2;145(1):279-87
references.pmid: 17210229
references.citation: J Neurosci. 2006 Aug 2;26(31):8168-75
references.pmid: 16885230
references.citation: J Psychiatr Res. 2010 Jul;44(10):673-81
references.pmid: 20100621
references.citation: Cereb Cortex. 2007 Jan;17(1):175-91
references.pmid: 16467563
references.citation: Arch Gen Psychiatry. 2008 Jul;65(7):772-84
references.pmid: 18606950
references.citation: Brain. 1979 Jun;102(2):347-60
references.pmid: 455044
references.citation: Brain Res. 1978 Mar 24;143(2):233-49
references.pmid: 415802
references.citation: J Comp Neurol. 2003 Oct 20;465(3):385-400
references.pmid: 12966563
references.citation: J Neurosci. 2004 Nov 3;24(44):9770-8
references.pmid: 15525762
references.citation: Arch Gen Psychiatry. 2000 Mar;57(3):237-45
references.pmid: 10711910
references.citation: Schizophr Bull. 2008 Sep;34(5):944-61
references.pmid: 18586694
references.citation: Cereb Cortex. 2011 May;21(5):999-1011
references.pmid: 20843900
references.citation: Arch Gen Psychiatry. 1995 Apr;52(4):258-66
references.pmid: 7702443
references.citation: Neuron. 2000 Oct;28(1):53-67
references.pmid: 11086983
references.citation: Eur J Neurosci. 2003 Sep;18(5):1213-22
references.pmid: 12956720
references.citation: J Comp Neurol. 1995 Aug 14;359(1):154-94
references.pmid: 8557845
references.citation: J Psychiatr Res. 2009 Jul;43(11):970-7
references.pmid: 19321177
references.citation: Neuroscience. 1995 Jul;67(1):7-22
references.pmid: 7477911
references.citation: Am J Psychiatry. 2003 Dec;160(12):2209-15
references.pmid: 14638592
references.citation: J Neuropsychiatry Clin Neurosci. 1994 Fall;6(4):348-57
references.pmid: 7841806
references.citation: J Neurophysiol. 2005 Feb;93(2):942-53
references.pmid: 15385591
references.citation: J Neurosci. 2005 Jul 20;25(29):6845-56
references.pmid: 16033894
references.citation: Am J Psychiatry. 2001 Sep;158(9):1411-22
references.pmid: 11532725
references.citation: Physiol Rev. 2003 Jul;83(3):1017-66
references.pmid: 12843414
references.citation: J Comp Neurol. 2009 Jun 1;514(4):353-67
references.pmid: 19330819
references.citation: Neuropsychopharmacology. 2008 Jan;33(1):141-65
references.pmid: 17805309
references.citation: Arch Gen Psychiatry. 2000 Nov;57(11):1061-9
references.pmid: 11074872
references.citation: BMC Med Genomics. 2009 May 20;2:28
references.pmid: 19457239
references.citation: J Comp Neurol. 1990 Mar 22;293(4):599-615
references.pmid: 2329196
references.citation: Neuron. 1995 Mar;14(3):477-85
references.pmid: 7695894
references.citation: J Physiol. 2009 May 1;587(Pt 9):1881-8
references.pmid: 19188247
references.citation: Am J Psychiatry. 2001 Feb;158(2):256-65
references.pmid: 11156808
references.citation: J Psychiatr Res. 1994 May-Jun;28(3):239-65
references.pmid: 7932285
references.citation: Arch Gen Psychiatry. 2004 Jul;61(7):649-57
references.pmid: 15237077
references.citation: Brain Res Dev Brain Res. 1996 Oct 23;96(1-2):261-76
references.pmid: 8922688
references.citation: Schizophr Bull. 1990;16(4):567-70
references.pmid: 2077635
references.citation: Cell Tissue Res. 2006 Nov;326(2):505-16
references.pmid: 16937111
references.citation: Int J Dev Neurosci. 2010 Oct;28(6):513-9
references.pmid: 20609421
references.citation: Annu Rev Neurosci. 2002;25:409-32
references.pmid: 12052915
references.citation: Cereb Cortex. 2002 Oct;12(10):1063-70
references.pmid: 12217970
references.citation: Proc Natl Acad Sci U S A. 1997 Jun 10;94(12):6496-9
references.pmid: 9177246
references.citation: Brain. 2006 Dec;129(Pt 12):3277-89
references.pmid: 17046856
references.citation: Cereb Cortex. 2008 Mar;18(3):626-37
references.pmid: 17591597
references.citation: J Comp Neurol. 2002 Jun 24;448(2):186-202
references.pmid: 12012429
references.citation: Proc Natl Acad Sci U S A. 1998 Dec 8;95(25):15066-71
references.pmid: 9844016
references.citation: J Neurosci. 1994 Nov;14(11 Pt 2):7077-86
references.pmid: 7525894
references.citation: Eur J Neurosci. 2001 Feb;13(3):428-42
references.pmid: 11168550
references.citation: Cereb Cortex. 1995 Nov-Dec;5(6):550-60
references.pmid: 8590827
references.citation: Eur J Neurosci. 1999 Dec;11(12):4213-25
references.pmid: 10594647
references.citation: Neurosci Res. 1999 Mar;33(3):187-94
references.pmid: 10211762
references.citation: J Comp Neurol. 1993 Feb 8;328(2):282-312
references.pmid: 7678612
references.citation: Arch Gen Psychiatry. 1986 Feb;43(2):114-24
references.pmid: 3947207
references.citation: Nat Rev Neurosci. 2005 Apr;6(4):312-24
references.pmid: 15803162
references.citation: J Comp Neurol. 1994 Mar 1;341(1):95-116
references.pmid: 8006226
references.citation: Am J Psychiatry. 1999 Nov;156(11):1709-19
references.pmid: 10553733
references.citation: Cereb Cortex. 1994 Jan-Feb;4(1):78-96
references.pmid: 8180493
references.citation: Am J Psychiatry. 2001 Jul;158(7):1105-13
references.pmid: 11431233
references.citation: Brain Res Rev. 2006 Sep;52(2):293-304
references.pmid: 16759710
references.citation: J Neurosci. 2000 Jan 1;20(1):485-94
references.pmid: 10627624
references.citation: Nat Rev Neurosci. 2005 Mar;6(3):215-29
references.pmid: 15738957
references.citation: Dev Psychol. 2002 May;38(3):352-62
references.pmid: 12005379
references.citation: Trends Neurosci. 2001 Aug;24(8):479-86
references.pmid: 11476888
references.citation: Schizophr Res. 2002 Nov 1;58(1):11-20
references.pmid: 12363385