title: Multilevel impact of the dopamine system on the emotion-potentiated startle reflex.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Psychiatry, Psychosomatics and Psychotherapy, University of Wuerzburg, Fuechsleinstrasse 15, 97080, Wuerzburg, Germany, Domschke_K@ukw.de.
authors.forename: Katharina
authors.initials: K
authors.lastname: Domschke
authors.forename: Bernward
authors.initials: B
authors.lastname: Winter
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Gajewska
authors.forename: Stefan
authors.initials: S
authors.lastname: Unterecker
authors.forename: Bodo
authors.initials: B
authors.lastname: Warrings
authors.forename: Andrea
authors.initials: A
authors.lastname: Dlugos
authors.forename: Swantje
authors.initials: S
authors.lastname: Notzon
authors.forename: Kathrin
authors.initials: K
authors.lastname: Nienhaus
authors.forename: Falko
authors.initials: F
authors.lastname: Markulin
authors.forename: Astrid
authors.initials: A
authors.lastname: Gieselmann
authors.forename: Christian
authors.initials: C
authors.lastname: Jacob
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Herrmann
authors.forename: Volker
authors.initials: V
authors.lastname: Arolt
authors.forename: Andreas
authors.initials: A
authors.lastname: Mühlberger
authors.forename: Andreas
authors.initials: A
authors.lastname: Reif
authors.forename: Paul
authors.initials: P
authors.lastname: Pauli
authors.forename: Jürgen
authors.initials: J
authors.lastname: Deckert
authors.forename: Peter
authors.initials: P
authors.lastname: Zwanzger
mesh_terms: D000328:Adult; D000483:Alleles; D001007:Anxiety / Q000235:genetics; D001143:Arousal / Q000187:drug effects / Q000235:genetics; D002230:Carbidopa / Q000494:pharmacology; D002394:Catechol O-Methyltransferase / Q000235:genetics; D004298:Dopamine / Q000502:physiology*; D004311:Double-Blind Method; D004338:Drug Combinations; D004644:Emotions / Q000187:drug effects* / Q000502:physiology*; D005260:Female; D005838:Genotype; D006801:Humans; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D013216:Reflex, Startle / Q000187:drug effects* / Q000235:genetics*
chemical_list: D004338:Drug Combinations; C009265:carbidopa, levodopa drug combination; D007980:Levodopa; D002394:Catechol O-Methyltransferase; D002230:Carbidopa; D004298:Dopamine