By David Douglas

NEW YORK (Reuters Health) - There appears to be a link between genetically controlled serotonergic modulation of amygdala activity and placebo-induced relief of anxiety, Swedish and Italian researchers report in the December 3rd issue of The Journal of Neuroscience.

"One possible implication of the finding," lead investigator Dr. Tomas Furmark told Reuters Health, "is that pharmaceutical companies should take genetic variation into account -- perform genotyping -- in clinical trials comparing a new active drug with a placebo, at least in disorders characterized by amygdala hyperresponsiveness such as anxiety disorders and depression."

Dr. Furmark of Uppsala University and colleagues used positron emission tomography to study 25 patients with social anxiety disorder who had been randomized to the placebo arms of trials evaluating pharmacologic treatment of anxiety.

Brain activity was assessed during a stressful public speaking task before and after 8 weeks of treatment. The team found that a placebo response was accompanied by reduced stress-related activity in the amygdala, a brain region crucial for emotional processing.

However, attenuated amygdala activity was seen only in subjects who were homozygous for the long allele of the serotonin transporter region 5-HTTLPR or the G variant of the tryptophan hydroxylase-2 gene promoter. The TPH2 G-703T polymorphism was a significant predictor of a clinical placebo response. Homozygosity for the G allele was associated with a greater improvement in anxiety symptoms.

"The generalizability of our findings," concluded Dr. Furmark, "should be explored in future research."

One question to be answered, he added, is whether "these genotypes are relevant for the placebo response in general or only for anxiety conditions."

J Neurosci 2008;28:13066-13074.