title: Sensorimotor gating is associated with CHRNA3 polymorphisms in schizophrenia and healthy volunteers.
abstract: Attentional gating deficits, commonly measured by prepulse inhibition (PPI) of the acoustic startle response (ASR), have been established as an endophenotype of schizophrenia. Prepulse inhibition is heritable and has been associated with polymorphisms in serotonin and dopamine system genes. Prepulse inhibition can be enhanced by nicotine, and therefore it has been proposed that schizophrenia patients smoke to ameliorate their early attentional deficits. The PPI-enhancing effects of nicotine in rodents are strain dependent, suggesting a genetic contribution to PPI within the nicotinic acetylcholine receptor (nAChR) system. Recent human genetic studies also imply that tobacco dependence is affected by polymorphisms in the alpha3/alpha5 subunits of the nAChR (CHRNA3/CHRNA5) gene cluster. We, therefore, investigated the impact of two common CHRNA3 polymorphisms (rs1051730/rs1317286) on PPI, startle reactivity, and habituation of the ASR in two independent samples of 107 healthy British volunteers and 73 schizophrenia patients hailing from Germany. In both samples, PPI was influenced by both CHRNA3 polymorphisms (combined p-value=0.0027), which were strongly linked. Moreover, CHRNA3 genotype was associated with chronicity, treatment, and negative symptoms in the schizophrenia sample. These results suggest that sensorimotor gating is influenced by variations of the CHRNA3 gene, which might also have an impact on the course and severity of schizophrenia.
authors.affiliation: Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.
authors.forename: Nadine
authors.initials: N
authors.lastname: Petrovsky
authors.forename: Boris B
authors.initials: BB
authors.lastname: Quednow
authors.forename: Ulrich
authors.initials: U
authors.lastname: Ettinger
authors.forename: Anne
authors.initials: A
authors.lastname: Schmechtig
authors.forename: Rainald
authors.initials: R
authors.lastname: Mössner
authors.forename: David A
authors.initials: DA
authors.lastname: Collier
authors.forename: Kai-Uwe
authors.initials: KU
authors.lastname: Kühn
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Maier
authors.forename: Michael
authors.initials: M
authors.lastname: Wagner
authors.forename: Veena
authors.initials: V
authors.lastname: Kumari
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods; D000293:Adolescent; D000328:Adult; D005060:Europe; D005260:Female; D020233:Gait Disorders, Neurologic / Q000209:etiology* / Q000235:genetics*; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D008297:Male; D015201:Meta-Analysis as Topic; D009433:Neural Inhibition / Q000235:genetics; D011110:Polymorphism, Genetic / Q000235:genetics*; D011569:Psychiatric Status Rating Scales; D011601:Psychophysics; D011978:Receptors, Nicotinic / Q000235:genetics*; D013216:Reflex, Startle / Q000235:genetics; D012559:Schizophrenia / Q000150:complications* / Q000235:genetics; D012565:Schizophrenic Psychology; D055815:Young Adult
chemical_list: D011978:Receptors, Nicotinic
references.citation: Biol Psychol. 2006 Mar;71(3):256-63
references.pmid: 16019125
references.citation: Psychol Med. 2008 Nov;38(11):1651-8
references.pmid: 18261249
references.citation: Biol Psychiatry. 1997 Feb 15;41(4):452-60
references.pmid: 9034539
references.citation: Neuroimage. 2005 Jul 15;26(4):1052-8
references.pmid: 15961045
references.citation: Psychopharmacology (Berl). 2001 Jul;156(2-3):266-72
references.pmid: 11549228
references.citation: Am J Psychiatry. 2003 Apr;160(4):636-45
references.pmid: 12668349
references.citation: Am J Psychiatry. 1998 Nov;155(11):1490-501
references.pmid: 9812108
references.citation: Am J Psychiatry. 2000 Oct;157(10):1660-8
references.pmid: 11007721
references.citation: Psychopharmacology (Berl). 2001 Jul;156(2-3):234-58
references.pmid: 11549226
references.citation: Psychopharmacology (Berl). 1994 Mar;114(2):369-74
references.pmid: 7838931
references.citation: Neurosci Lett. 2003 Dec 15;353(1):45-8
references.pmid: 14642434
references.citation: Neuroscience. 1993 Sep;56(1):23-32
references.pmid: 7901807
references.citation: Biol Psychiatry. 2003 Jul 15;54(2):121-8
references.pmid: 12873801
references.citation: Neurosci Biobehav Rev. 2005;29(6):1021-34
references.pmid: 15964073
references.citation: Arch Gen Psychiatry. 1992 Mar;49(3):206-15
references.pmid: 1567275
references.citation: Eur J Pharmacol. 2000 Mar 30;393(1-3):11-21
references.pmid: 10770993
references.citation: Am J Hum Genet. 2003 Jul;73(1):34-48
references.pmid: 12802786
references.citation: Prog Neurobiol. 2000 May;61(1):75-111
references.pmid: 10759066
references.citation: Prog Neurobiol. 2004 Dec;74(6):363-96
references.pmid: 15649582
references.citation: Pharmacol Biochem Behav. 1999 Feb;62(2):273-84
references.pmid: 9972694
references.citation: Pharmacol Biochem Behav. 1995 Feb;50(2):191-8
references.pmid: 7740057
references.citation: Psychopharmacology (Berl). 1999 Jan;141(1):11-5
references.pmid: 9952059
references.citation: Psychopharmacology (Berl). 1997 Aug;132(4):389-95
references.pmid: 9298517
references.citation: Mol Pharmacol. 2004 Jun;65(6):1526-35
references.pmid: 15155845
references.citation: Prog Neurobiol. 1999 Oct;59(2):107-28
references.pmid: 10463792
references.citation: Biol Psychiatry. 1993 Jun 1-15;33(11-12):815-28
references.pmid: 8373920
references.citation: Neuropsychopharmacology. 2008 Aug;33(9):2167-74
references.pmid: 17957213
references.citation: Semin Cell Dev Biol. 2009 Jun;20(4):432-40
references.pmid: 19560048
references.citation: Psychophysiology. 2005 Sep;42(5):588-94
references.pmid: 16176381
references.citation: Mol Psychiatry. 2008 Apr;13(4):368-73
references.pmid: 18227835
references.citation: Psychopharmacology (Berl). 2001 Jul;156(2-3):117-54
references.pmid: 11549216
references.citation: Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):587-92
references.pmid: 9012828
references.citation: Curr Med Res Opin. 2004 Jul;20(7):1057-74
references.pmid: 15265251
references.citation: Psychopharmacology (Berl). 1996 Nov;128(1):54-60
references.pmid: 8944406
references.citation: Schizophr Res. 2006 Oct;87(1-3):307-15
references.pmid: 16854565
references.citation: Schizophr Bull. 2010 Mar;36(2):341-6
references.pmid: 18635674
references.citation: Am J Psychiatry. 2002 Aug;159(8):1375-81
references.pmid: 12153831
references.citation: PLoS One. 2009;4(2):e4653
references.pmid: 19247474
references.citation: Prog Neurobiol. 2007 Oct;83(2):69-91
references.pmid: 17681661
references.citation: Neuropsychol Rev. 2009 Sep;19(3):324-35
references.pmid: 19507034
references.citation: Biol Psychiatry. 2008 Aug 1;64(3):235-40
references.pmid: 18325483
references.citation: Br J Pharmacol. 2004 Jul;142(5):843-50
references.pmid: 15197106
references.citation: Psychopharmacology (Berl). 2008 May;198(1):93-101
references.pmid: 18338158
references.citation: Biol Psychiatry. 2007 May 15;61(10):1204-7
references.pmid: 17161386
references.citation: Br J Addict. 1991 Sep;86(9):1119-27
references.pmid: 1932883
references.citation: Psychopharmacology (Berl). 2001 Jul;156(2-3):194-215
references.pmid: 11549223
references.citation: Psychophysiology. 1975 May;12(3):238-48
references.pmid: 1153628
references.citation: Arch Gen Psychiatry. 2007 Nov;64(11):1242-50
references.pmid: 17984393
references.citation: Biol Psychiatry. 2008 Nov 1;64(9):766-73
references.pmid: 18514166
references.citation: Psychopharmacology (Berl). 1998 Jun;137(4):362-8
references.pmid: 9676896
references.citation: Psychophysiology. 1978 Jul;15(4):339-43
references.pmid: 693742
references.citation: Schizophr Bull. 2007 Jan;33(1):69-94
references.pmid: 17135482
references.citation: Arch Gen Psychiatry. 2006 Dec;63(12):1325-35
references.pmid: 17146007
references.citation: Biol Psychiatry. 2006 Mar 15;59(6):536-45
references.pmid: 16139819
references.citation: Arch Gen Psychiatry. 2005 Jun;62(6):649-59
references.pmid: 15939842
references.citation: Biol Psychiatry. 2008 Sep 1;64(5):434-7
references.pmid: 18420180
references.citation: Biol Psychiatry. 2000 Apr 1;47(7):662-9
references.pmid: 10745060
references.citation: Psychiatry Res. 2006 Aug 30;143(2-3):147-58
references.pmid: 16879870
references.citation: J Pharmacol Exp Ther. 2001 May;297(2):646-56
references.pmid: 11303054
references.citation: Behav Res Methods. 2007 May;39(2):175-91
references.pmid: 17695343
references.citation: Mol Pharmacol. 2005 Jan;67(1):32-41
references.pmid: 15470079
references.citation: Nat Genet. 2008 Jul;40(7):827-34
references.pmid: 18583979
references.citation: J Evol Biol. 2005 Sep;18(5):1368-73
references.pmid: 16135132
references.citation: Pharmacol Biochem Behav. 1994 Dec;49(4):877-82
references.pmid: 7886101
references.citation: Biol Psychiatry. 2009 Sep 15;66(6):614-20
references.pmid: 19545856
references.citation: Schizophr Bull. 2009 May;35(3):549-62
references.pmid: 19325164
references.citation: Psychopharmacology (Berl). 2002 Jan;159(3):248-57
references.pmid: 11862357
references.citation: Behav Genet. 2004 May;34(3):343-54
references.pmid: 14990873
references.citation: Psychopharmacology (Berl). 2006 Mar;184(3-4):589-99
references.pmid: 16456657
references.citation: Am J Psychiatry. 1993 Dec;150(12):1862-7
references.pmid: 8238643
references.citation: Am J Psychiatry. 2008 Aug;165(8):1040-7
references.pmid: 18381905
references.citation: Am J Med Genet B Neuropsychiatr Genet. 2009 Jun 5;150B(4):453-66
references.pmid: 19259974
references.citation: Nature. 2003 Dec 18;426(6968):789-96
references.pmid: 14685227
references.citation: Am J Psychiatry. 2008 Sep;165(9):1163-71
references.pmid: 18519524
references.citation: J Affect Disord. 2006 Jun;92(2-3):299-303
references.pmid: 16503358
references.citation: Pharmacol Biochem Behav. 1998 Nov;61(3):281-9
references.pmid: 9768562
references.citation: Arch Gen Psychiatry. 2000 Jun;57(6):609-14
references.pmid: 10839340