RT Journal Article
SR Electronic
T1 A Link between Serotonin-Related Gene Polymorphisms, Amygdala Activity, and Placebo-Induced Relief from Social Anxiety
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 13066
OP 13074
DO 10.1523/JNEUROSCI.2534-08.2008
VO 28
IS 49
A1 Furmark, Tomas
A1 Appel, Lieuwe
A1 Henningsson, Susanne
A1 Åhs, Fredrik
A1 Faria, Vanda
A1 Linnman, Clas
A1 Pissiota, Anna
A1 Frans, Örjan
A1 Bani, Massimo
A1 Bettica, Paolo
A1 Pich, Emilio Merlo
A1 Jacobsson, Eva
A1 Wahlstedt, Kurt
A1 Oreland, Lars
A1 Långström, Bengt
A1 Eriksson, Elias
A1 Fredrikson, Mats
YR 2008
UL http://www.jneurosci.org/content/28/49/13066.abstract
AB Placebo may yield beneficial effects that are indistinguishable from those of active medication, but the factors underlying proneness to respond to placebo are widely unknown. Here, we used functional neuroimaging to examine neural correlates of anxiety reduction resulting from sustained placebo treatment under randomized double-blind conditions, in patients with social anxiety disorder. Brain activity was assessed during a stressful public speaking task by means of positron emission tomography before and after an 8 week treatment period. Patients were genotyped with respect to the serotonin transporter-linked polymorphic region (5-HTTLPR) and the G-703T polymorphism in the tryptophan hydroxylase-2 (TPH2) gene promoter. Results showed that placebo response was accompanied by reduced stress-related activity in the amygdala, a brain region crucial for emotional processing. However, attenuated amygdala activity was demonstrable only in subjects who were homozygous for the long allele of the 5-HTTLPR or the G variant of the TPH2 G-703T polymorphism, and not in carriers of short or T alleles. Moreover, the TPH2 polymorphism was a significant predictor of clinical placebo response, homozygosity for the G allele being associated with greater improvement in anxiety symptoms. Path analysis supported that the genetic effect on symptomatic improvement with placebo is mediated by its effect on amygdala activity. Hence, our study shows, for the first time, evidence of a link between genetically controlled serotonergic modulation of amygdala activity and placebo-induced anxiety relief.