Serotonin transporter gene alters insula activity to threat in social anxiety disorder

Amygdala and insula hyper-reactivity to threat is implicated in social anxiety disorder (SAD) yet inconsistencies in activation have been reported. One source of variance are individual differences in 5-HTTLPR genotype where the short (S), relative to long (L) allele, corresponds with greater amygdala activation. However, the impact of genotype on insula to threat in SAD is not known. During functional MRI, 34 SAD patients and 28 healthy controls completed a perceptual assessment task comprising angry, fear, and happy faces. Results showed no diagnostic group differences in limbic/paralimbic regions but within SAD, greater insula, but not amygdala, activation to fearful faces was observed in patients with SS genotype compared with LaLa genotype. Findings indicate genotype influenced insula activation to threat in SAD.