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Sensorimotor Gating Depends on Polymorphisms of the Serotonin-2A Receptor and Catechol-O-Methyltransferase, but Not on Neuregulin-1 Arg38Gln Genotype: A Replication Study

Research output: Contribution to journalArticle

Boris B. Quednow, Anne Schmechtig, Ulrich Ettinger, Nadine Petrovsky, David A. Collier, Franz X. Vollenweider, Michael Wagner, Veena Kumari

Original languageEnglish
Article numberN/A
Pages (from-to)614 - 620
Number of pages7
JournalBiological psychiatry
Volume66
Issue number6
DOIs
Publication statusPublished - 15 Sep 2009

King's Authors

Abstract

Background: Prepulse inhibition (PPI) of the acoustic startle response (ASR) is an operational measure of sensorimotor gating and a promising endophenotype of schizophrenia. We have recently shown that the linked serotonin-2A receptor (5-HT2AR) A-1438 G and T102C polymorphisms modulate PPI in schizophrenia patients. Moreover, it was shown that genetic variation in the catechol-O-methyltransferase (COMT) and the neuregulin-1 (NRG-1) proteins influences PIPI in schizophrenia patients and healthy volunteers. Therefore, we aimed to replicate these results and investigated the impact of the related polymorphisms on PPI in healthy human volunteers. Methods: We analyzed the 5-HT(2A)RA-1438 G/T102C (rs6311/rs6313), the COMT Val158Met (rs4680), and the NRG-1 Arg38Gln(rs3924999) polymorphisms, assessing startle reactivity, habituation, and PIPI of ASR in 107 healthy Caucasian volunteers. Results: Subjects homozygous for the 5-HT2AR T102C-T/A-1438 G-A allele showed increased PPI levels. In particular, male subjects with the COMT Met158Met-genotype also showed elevated PPI. The NRG-1 Arg38Gln genotype did not have a significant impact on PPI. Startle reactivity was not affected by any of the investigated polymorphisms. Conclusions: We confirmed in an independent sample of healthy volunteers that PPI is influenced by genetic variation in the 5-HT2AR gene. The influence of the COMT Val158Met genotype on PPI appears to be sex-specific. These results underscore the significance of the serotonin and dopamine systems in the modulation of sensorimotor gating.

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