Multilevel impact of the dopamine system on the emotion-potentiated startle reflex

Domschke K., Winter B., Gajewska A., Unterecker S., Warrings B., Dlugos A., Notzon S., Nienhaus K., Markulin F., Gieselmann A., Jacob C., Herrmann M., Arolt V., Mühlberger A., Reif A., Pauli P., Deckert J., Zwanzger P.

Abstract

Rationale/objectives: The pathogenetic mechanism of emotion-related disorders such as anxiety disorders is considered to be complex with an interaction of genetic, biochemical, and environmental factors. Particular evidence has accumulated for alterations in the dopaminergic system - partly conferred by catechol-O-methyltransferase (COMT) gene variation - and for distorted emotional processing to constitute risk factors for anxiety and anxiety-related disorders. Methods: Applying a multilevel approach, we analyzed the main and interactive effects of the functional COMT val158met polymorphism and L-dopa (single-dose 50 mg levodopa and 12.5 mg carbidopa; double-blind, placebo-controlled design) on the emotion-potentiated (unpleasant, neutral, and pleasant IAPS pictures) startle response as an intermediate phenotype of anxiety in a sample of 100 healthy probands (f=52, m=48). Results: The COMT 158val allele was associated with an increased startle potentiation by unpleasant stimuli as compared with neutral stimuli irrespective of L-dopa or placebo intervention. COMT 158met/met genotype carriers, while displaying no difference in startle magnitude in response to unpleasant or neutral pictures in the placebo condition, showed startle potentiation by unpleasant pictures under L-dopa administration only. Conclusions: The present proof-of-concept study provides preliminary support for a complex, multilevel impact of the dopaminergic system on the emotion-potentiated startle reflex suggesting increased phasic dopamine transmission driven by the more active COMT 158val allele and/or a single dose of L-dopa to predispose to maladaptive emotional processing and thereby potentially also to anxiety-related psychopathological states.