Journal
NEUROPSYCHOPHARMACOLOGY
Volume 35, Issue 7, Pages 1429-1439Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/npp.2010.12
Keywords
prepulse inhibition; sensorimotor gating; CHRNA3; nicotinic acetylcholine receptor; rs1051730; schizophrenia
Categories
Funding
- German Research Foundation (DFG) [WA 737/7, ET 31/2-1]
- Swiss National Science Foundation [PP00P1_123516]
- European Commission [FP6-2005-LIFESCI HEALTH-7, 037, 761]
- Wellcome Trust [067427/z/02]
- German Federal Ministry of Education and Research (BMBF) [01GV0907]
- Mundipharma (Basel, Switzerland)
- Swiss National Science Foundation (SNF) [PP00P1_123516] Funding Source: Swiss National Science Foundation (SNF)
- Medical Research Council [G9817803B] Funding Source: researchfish
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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 alpha 3/alpha 5 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. Neuropsychopharmacology (2010) 35, 1429-1439; doi: 10.1038/npp.2010.12; published online 10 March 2010
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