A link between serotonin-related gene polymorphisms, amygdala activity, and placebo-induced relief from social anxiety. Export

@article{citeulike:3746842, 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.}, author = {Furmark, T. and Appel, L. and Henningsson, S. and Ahs, F. and Faria, V. and Linnman, C. and Pissiota, A. and Frans, O. and Bani, M. and Bettica, P. and Pich, E. M. and Jacobsson, E. and Wahlstedt, K. and Oreland, L. and L\r{a}ngstr\"{o}m, B. and Eriksson, E. and Fredrikson, M.}, citeulike-article-id = {3746842}, citeulike-linkout-0 = {http://dx.doi.org/10.1523/JNEUROSCI.2534-08.2008}, citeulike-linkout-1 = {http://www.jneurosci.org/cgi/content/abstract/28/49/13066}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/19052197}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=19052197}, day = {3}, doi = {10.1523/JNEUROSCI.2534-08.2008}, issn = {1529-2401}, journal = {The Journal of neuroscience : the official journal of the Society for Neuroscience}, keywords = {amygdala, anxiete, placebo, serotonine}, month = {December}, number = {49}, pages = {13066--13074}, posted-at = {2009-03-16 12:48:50}, priority = {2}, title = {A link between serotonin-related gene polymorphisms, amygdala activity, and placebo-induced relief from social anxiety.}, url = {http://dx.doi.org/10.1523/JNEUROSCI.2534-08.2008}, volume = {28}, year = {2008} }

TY - JOUR ID - citeulike:3746842 L3 - citeulike-article-id:3746842 N2 - 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. IS - 49 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience SN - 1529-2401 EP - 13074 TI - A link between serotonin-related gene polymorphisms, amygdala activity, and placebo-induced relief from social anxiety. VL - 28 SP - 13066 KW - amygdala KW - anxiete KW - placebo KW - serotonine AU - Furmark, T AU - Appel, L AU - Henningsson, S AU - Ahs, F AU - Faria, V AU - Linnman, C AU - Pissiota, A AU - Frans, O AU - Bani, M AU - Bettica, P AU - Pich, EM AU - Jacobsson, E AU - Wahlstedt, K AU - Oreland, L AU - Långström, B AU - Eriksson, E AU - Fredrikson, M PY - 2008/12/03/ UR - http://dx.doi.org/10.1523/JNEUROSCI.2534-08.2008 ER -