D2 receptor density and prepulse inhibition in humans: negative findings from a molecular genetic approach.

There is plenty of evidence from schizophrenia research and psychopharmacological experiments showing the influence of the dopaminergic neurotransmission on the prepulse inhibition (PPI). A lot of insights into the underlying neural mechanisms of the PPI have been gained from animal models, which are in need to be validated in humans. Due to new technological advances, findings from psychopharmacological challenge tests can now be verified with techniques from molecular genetics which provide an elegant non-invasive approach. To close the gap between animal research and research in humans in this field a molecular genetic approach was applied to investigate the neural mechanisms of the PPI in healthy subjects. In N=96 female participants recruited out of a sample of N=800 subjects according to their genotypes we tested the association between the DRD2 Taq Ia and the COMT Val158Met polymorphisms, and the magnitude of the eye-blink reflex in an acoustic PPI paradigm. Neither significant influences of both dopaminergic single nucleotide polymorphisms nor an epistasis effect could be detected. Although findings do not support the hypothesis that two of the most prominent dopaminergic candidate loci (DRD2 Taq Ia and COMT Val158Met) effect PPI the study does not exclude the relevance of the dopaminergic system in general. Further molecular genetic studies investigating other variants on dopaminergic genes have to be conducted.