title: Affect-modulated startle: interactive influence of catechol-O-methyltransferase Val158Met genotype and childhood trauma.
abstract: The etiology of emotion-related disorders such as anxiety or affective disorders is considered to be complex with an interaction of biological and environmental factors. Particular evidence has accumulated for alterations in the dopaminergic and noradrenergic system--partly conferred by catechol-O-methyltransferase (COMT) gene variation--for the adenosinergic system as well as for early life trauma to constitute risk factors for those conditions. Applying a multi-level approach, in a sample of 95 healthy adults, we investigated effects of the functional COMT Val158Met polymorphism, caffeine as an adenosine A2A receptor antagonist (300 mg in a placebo-controlled intervention design) and childhood maltreatment (CTQ) as well as their interaction on the affect-modulated startle response as a neurobiologically founded defensive reflex potentially related to fear- and distress-related disorders. COMT val/val genotype significantly increased startle magnitude in response to unpleasant stimuli, while met/met homozygotes showed a blunted startle response to aversive pictures. Furthermore, significant gene-environment interaction of COMT Val158Met genotype with CTQ was discerned with more maltreatment being associated with higher startle potentiation in val/val subjects but not in met carriers. No main effect of or interaction effects with caffeine were observed. Results indicate a main as well as a GxE effect of the COMT Val158Met variant and childhood maltreatment on the affect-modulated startle reflex, supporting a complex pathogenetic model of the affect-modulated startle reflex as a basic neurobiological defensive reflex potentially related to anxiety and affective disorders.
authors: Department of Psychiatry and Psychotherapy, University of Muenster, Muenster, Germany.
authors: Benedikt
authors: B
authors: Klauke
authors: Bernward
authors: B
authors: Winter
authors: Agnes
authors: A
authors: Gajewska
authors: Peter
authors: P
authors: Zwanzger
authors: Andreas
authors: A
authors: Reif
authors: Martin J
authors: MJ
authors: Herrmann
authors: Andrea
authors: A
authors: Dlugos
authors: Bodo
authors: B
authors: Warrings
authors: Christian
authors: C
authors: Jacob
authors: Andreas
authors: A
authors: Mühlberger
authors: Volker
authors: V
authors: Arolt
authors: Paul
authors: P
authors: Pauli
authors: Jürgen
authors: J
authors: Deckert
authors: Katharina
authors: K
authors: Domschke
mesh_terms: D058908:Adenosine A2 Receptor Agonists / Q000494:pharmacology; D000328:Adult; D054523:Adult Survivors of Child Abuse / Q000523:psychology*; D002110:Caffeine / Q000494:pharmacology; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics; D013216:Reflex, Startle / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D055815:Young Adult
chemical_list: D058908:Adenosine A2 Receptor Agonists; D002110:Caffeine; D002394:Catechol O-Methyltransferase