title: Genotype over-diagnosis in amygdala responsiveness: affective processing in social anxiety disorder.
abstract: BACKGROUND
  Although the amygdala is thought to be a crucial brain region for negative affect, neuroimaging studies do not always show enhanced amygdala response to aversive stimuli in patients with anxiety disorders. Serotonin (5-HT)-related genotypes may contribute to interindividual variability in amygdala responsiveness. The short (s) allele of the 5-HT transporter linked polymorphic region (5-HTTLPR) and the T variant of the G-703T polymorphism in the tryptophan hydroxylase-2 (TPH2) gene have previously been associated with amygdala hyperresponsivity to negative faces in healthy controls. We investigated the influence of these polymorphisms on amygdala responsiveness to angry faces in patients with social anxiety disorder (SAD) compared with healthy controls.
  
  
  METHODS
  We used positron emission tomography with oxygen 15-labelled water to assess regional cerebral blood flow in 34 patients with SAD and 18 controls who viewed photographs of angry and neutral faces presented in counterbalanced order. We genotyped all participants with respect to the 5-HTTLPR and TPH2 polymorphisms.
  
  
  RESULTS
  Patients with SAD and controls had increased left amygdala activation in response to angry compared with neutral faces. Genotype but not diagnosis explained a significant portion of the variance in amygdala responsiveness, the response being more pronounced in carriers of s and/or T alleles.
  
  
  CONCLUSIONS
  Our analyses were limited owing to the small sample and the fact that we were unable to match participants on genotype before enrollment. In addition, other imaging techniques not used in our study may have revealed additional effects of emotional stimuli.
  
  
  CONCLUSIONS
  Amygdala responsiveness to angry faces was more strongly related to serotonergic polymorphisms than to diagnosis of SAD. Emotion activation studies comparing amygdala excitability in patient and control groups could benefit from taking variation in 5-HT-related genes into account.
authors.affiliation: Department of Psychology, Uppsala University, Uppsala, Sweden. tomas.furmark@psyk.uu.se
authors.forename: Tomas
authors.initials: T
authors.lastname: Furmark
authors.forename: Susanne
authors.initials: S
authors.lastname: Henningsson
authors.forename: Lieuwe
authors.initials: L
authors.lastname: Appel
authors.forename: Fredrik
authors.initials: F
authors.lastname: Ahs
authors.forename: Clas
authors.initials: C
authors.lastname: Linnman
authors.forename: Anna
authors.initials: A
authors.lastname: Pissiota
authors.forename: Vanda
authors.initials: V
authors.lastname: Faria
authors.forename: Lars
authors.initials: L
authors.lastname: Oreland
authors.forename: Massimo
authors.initials: M
authors.lastname: Bani
authors.forename: Emilio Merlo
authors.initials: EM
authors.lastname: Pich
authors.forename: Elias
authors.initials: E
authors.lastname: Eriksson
authors.forename: Mats
authors.initials: M
authors.lastname: Fredrikson
mesh_terms: D000328:Adult; D000679:Amygdala / Q000000981:diagnostic imaging*; D001008:Anxiety Disorders / Q000000981:diagnostic imaging* / Q000235:genetics* / Q000523:psychology; D004644:Emotions; D005260:Female; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D049268:Positron-Emission Tomography; D011569:Psychiatric Status Rating Scales; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D014365:Tryptophan Hydroxylase / Q000235:genetics; D055815:Young Adult
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase