Catechol-O-methyltransferase (COMT) Val158Met Polymorphism and Prepulse Inhibition of the Change-related Cerebral Response

Change-related potentials elicited by an abrupt sound feature's change are attenuated by a leading weak sound (prepulse inhibition: PPI). We investigated whether the PPI index is associated with the catechol-methyltransferase (COMT) Val158Met polymorphism (rs4680), which is involved in the metabolism of dopamine in the prefrontal cortex. Healthy subjects with normal hearing were recruited (n = 70). A train of 100-Hz clicks 650 ms in duration was used. The test stimulus was an abrupt increase in sound intensity (+10 dB) from the baseline (70 dB) provided at 400 ms after the sound onset. Three consecutive clicks at 30, 40, and 50 ms before the change's onset were greater (+3 or +5 dB) from the baseline as a prepulse. The targeting auditory evoked potential component was Change-N1 peaking approx. 130 ms after the change onset. We calculated the inhibition level as the% inhibition of the Change-N1 amplitude by a prepulse. The %PPI in the Met-carriers was significantly greater than that in the Val/Val-individuals. Our results suggest that dopamine might play a role in the PPI of the change-related response. We propose that this index has the potential to identify an intermediate phenotype in psychiatric disorders such as schizophrenia.

Automated summary

This study investigates the association between the prepulse inhibition (PPI) index and the COMT gene polymorphism and explores the role of dopamine metabolism in the prefrontal cortex. The results show that the PPI level in Met-carriers is significantly higher than that in Val/Val individuals, suggesting that dopamine may play a role in PPI and this index has the potential to be used for identifying intermediate phenotypes in psychiatric disorders.