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

Psychiatry Res Neuroimaging. 2022 Jul:323:111484. doi: 10.1016/j.pscychresns.2022.111484. Epub 2022 Apr 17.

Abstract

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.

Keywords: AEP; COMT; N1; Prepulse inhibition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acoustic Stimulation / methods
  • Catechol O-Methyltransferase* / genetics
  • Dopamine / metabolism
  • Evoked Potentials, Auditory / genetics
  • Humans
  • Prepulse Inhibition* / genetics

Substances

  • COMT protein, human
  • Catechol O-Methyltransferase
  • Dopamine