title: Catechol-O-methyltransferase gene variation: impact on amygdala response to aversive stimuli.
abstract: The functional catechol-O-methyltransferase (COMT) val158met polymorphism has been found to be associated with anxiety disorders and depression as well as with neural correlates of emotional processing, with, however, contradictory results. Thus, the aim of the present study was to re-evaluate the impact of the COMT val158met variant on neural activation correlates of emotional face processing in a sample of healthy probands. In 85 healthy subjects genotyped for the COMT val158met polymorphism, amygdala responses were assessed by means of fMRI. Participants were presented with anger- and fear-relevant faces in a robust emotion-processing paradigm. For exploratory reasons, a supplementary whole-brain analysis of the allele-dose model and a gender-stratified analysis were conducted. The COMT 158val allele showed an allele-dose effect on increased predominantly left-sided amygdala activity in response to fearful/angry facial stimuli (p(uncorrected)=.00004). This effect was independent from the distribution of the frequently studied 5-HTTLPR polymorphism for which a linear effect of S-alleles on amygdala responsiveness was replicated. The influence of COMT 158val alleles was only discerned in the female subgroup of probands. The whole-brain analysis suggested associations of the COMT 158val allele with increased activity in areas of the ventral visual stream and the lateral prefrontal cortex. The present results provide further support for a-potentially female-specific-role of the COMT val158met polymorphism in the genetic and neural underpinnings of anxiety- and depression-related intermediate phenotypes and may aid in further clarifying the differential role of COMT genotype driven dopaminergic tonus in the processing of emotionally salient stimuli.
authors.affiliation: Department of Psychiatry, University of Muenster, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Domschke
authors.forename: Bernhard T
authors.initials: BT
authors.lastname: Baune
authors.forename: Linda
authors.initials: L
authors.lastname: Havlik
authors.forename: Anja
authors.initials: A
authors.lastname: Stuhrmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Suslow
authors.forename: Harald
authors.initials: H
authors.lastname: Kugel
authors.forename: Peter
authors.initials: P
authors.lastname: Zwanzger
authors.forename: Dominik
authors.initials: D
authors.lastname: Grotegerd
authors.forename: Christina
authors.initials: C
authors.lastname: Sehlmeyer
authors.forename: Volker
authors.initials: V
authors.lastname: Arolt
authors.forename: Udo
authors.initials: U
authors.lastname: Dannlowski
mesh_terms: D000328:Adult; D000679:Amygdala / Q000502:physiology*; D001931:Brain Mapping; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D004644:Emotions / Q000502:physiology*; D005145:Face; D005260:Female; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010775:Photic Stimulation; D011110:Polymorphism, Genetic; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D012727:Sex Characteristics
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D002394:Catechol O-Methyltransferase