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A Link between Serotonin-Related Gene Polymorphisms, Amygdala Activity, and Placebo-Induced Relief from Social Anxiety.

Journal article
Authors Furmark
Appel
Susanne Henningsson
Ahs
Faria
Linnman
Pissiota
Frans
Bani
Bettica
Pich
Jacobsson
Wahlstedt
Oreland
L?ngstr?m
Elias Eriksson
Fredrikson
Published in The Journal of neuroscience : the official journal of the Society for Neuroscience
Volume 28
Issue 49
Pages 13066-13074
ISSN 1529-2401
Publication year 2008
Published at Institute of Neuroscience and Physiology, Department of Pharmacology
Pages 13066-13074
Language en
Links dx.doi.org/10.1523/JNEUROSCI.2534-0...
Keywords Serotonin-related gene, amygdala activity, social anxiety
Subject categories Pharmacology and Toxicology

Abstract

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.

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