Variation in genes involved in dopamine clearance influence the startle response in older adults

The dopamine transporter (DAT) and the enzyme catechol-O-methyltransferase (COMT) both terminate synaptic dopamine action. Here, we investigated the influence of two polymorphisms in the respective genes: DAT1 (SLC6A3) VNTR and COMT val(158)met (rs4680). Startle magnitudes to intense noise bursts as measured with the eye blink response were recorded during the presentation of pictures of three valence conditions (unpleasant, pleasant and neutral) and during baseline without additional pictorial stimulation in a sample of healthy older adults (N = 94). There was a significant Bonferroni corrected main effect of COMT genotype on the overall startle responses, with met/met homozygotes showing the highest and participants with the val/val genotype showing the lowest startle response, while participants with the val/met genotype displayed intermediate reactions. There was also a DAT1 VNTR main effect, which, after Bonferroni correction, still showed a tendency toward significance with carriers of at least one 9-repeat (R) allele showing smaller overall startle responses compared to 10R/10R homozygotes. Thus, older adult carriers of COMT variants, which result in lower enzyme activity and therefore probably enhanced dopamine signaling, showed stronger startle activity. Although the functional significance of DAT1 VNTR is less defined, our results point to a potential influence of SLC6A3 on startle magnitude.