Genetic differences in dopaminergic neurotransmission link perceptual inference with delusion-proneness K Schmack1, H Rössler2, M Sekutowicz1, E Brandl3, D Müller3, P Sterzer2 |
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1Department of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, Germany |
| Altered perceptual inference has been proposed as a key factor in the emergence of delusional beliefs. As dopaminergic neurotransmission has been implicated in delusion formation, we asked whether the role of beliefs in perceptual inference may be modulated by dopamine-related genes. In a behavioural study in 102 healthy volunteers we used a placebo-like manipulation to probe the effect of beliefs on the perception of an ambiguous visual motion display. Three functional haplotypes of the catechol-o-methyltransferase gene (COMT, a dopamine-degrading enzyme) were genotyped and participants completed a delusion questionnaire designed to quantify delusion-proneness in the healthy population. We found that carriers of the COMT high-activity haplotype (i.e. highest COMT-activity, lowest synaptic dopamine availability) showed a weaker effect of experimentally induced beliefs on perception, compared to non-carriers. Moreover, delusion-proneness correlated positively with effect of beliefs on perception, and was negatively associated with the COMT high-activity haplotype. In other words, individuals carrying the COMT haplotype with low synaptic dopamine availability were both less delusion-prone and less susceptible to the effect of experimentally induced beliefs on perception. These findings provide (a) evidence for an effect of dopamine-genetics on perceptual inference and (b) a possible neurobiological substrate linking altered perceptual inference with delusion-proneness. |
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