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

• Published in: Psychiatry research. Neuroimaging Vol. 323; p. 111484
• Main Authors: Motomura, Eishi, Tanii, Hisashi, Kawano, Yasuhiro, Inui, Koji, Okada, Motohiro
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.07.2022
• Subjects: Acoustic Stimulation - methods; AEP; Catechol O-Methyltransferase - genetics; COMT; Dopamine - metabolism; Evoked Potentials, Auditory - genetics; Humans; Prepulse inhibition; Prepulse Inhibition - genetics; N1; AEP; COMT; Prepulse inhibition
• ISSN: 0925-4927; 1872-7506; 1872-7506
• DOI: 10.1016/j.pscychresns.2022.111484

•COMT genotype influenced the prepulse inhibition (PPI) of change-related response.•The %PPI in Met carriers was greater than that in Val/Val healthy individuals.•This index has the potential to be an endophenotype of schizophrenia. 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.