Sensorimotor gating is associated with CHRNA3 polymorphisms in schizophrenia and healthy volunteers.
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.
Petrovsky
Nadine
N
Department of Psychiatry and Psychotherapy, University of Bonn, Bonn, Germany.
Quednow
Boris B
BB
Ettinger
Ulrich
U
Schmechtig
Anne
A
Mössner
Rainald
R
Collier
David A
DA
Kühn
Kai-Uwe
KU
Maier
Wolfgang
W
Wagner
Michael
M
Kumari
Veena
V
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
D011978:Receptors, Nicotinic
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