Serotonin transporter polymorphism related to amygdala excitability and symptom severity in patients with social phobia.

A functional polymorphism in the promoter region of the human serotonin transporter (5-HTT) gene has been related to negative affect and amygdala activity. We studied amygdala activation during social anxiety provocation in relation to affective ratings and 5-HTT genetic variation. [H2(15)O]positron emission tomography was used to estimate amygdala blood flow during private and public speaking (baseline and anxiety conditions) in 17 patients with social phobia. Genotyping identified patients with long and short alleles in the promoter region of the 5-HTT. Individuals with one or two copies of the short allele exhibited significantly increased levels of anxiety-related traits, state anxiety, and enhanced right amygdala responding to anxiety provocation, compared with subjects homozygous for the long allele. Thus, 5-HTT genetic variation was associated with symptom severity and amygdala excitability in social phobia.