Genotype over-diagnosis in amygdala responsiveness: affective processing in social anxiety disorder.
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.
Furmark
Tomas
T
Department of Psychology, Uppsala University, Uppsala, Sweden. tomas.furmark@psyk.uu.se
Henningsson
Susanne
S
Appel
Lieuwe
L
Ahs
Fredrik
F
Linnman
Clas
C
Pissiota
Anna
A
Faria
Vanda
V
Oreland
Lars
L
Bani
Massimo
M
Pich
Emilio Merlo
EM
Eriksson
Elias
E
Fredrikson
Mats
M
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
C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase