Cited by 210Pain Management and Placebo EffectNeurotransmitter Receptor Influence on BehaviorAnxiety, Depression, Psychometrics, Treatment, Cognitive Processes

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

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Furmark, Tomas, Appel, Lieuwe, Henningsson, Susanne, Åhs, Fredrik, Faria, Vanda, Linnman, Clas, Pissiota, Anna, Frans, Örjan, Bani, Massimo, Bettica, Paolo, Pich, Emilio Merlo, Jacobsson, Eva, Wahlstedt, Kurt, Oreland, Lars, Långström, Bengt, Eriksson, Elias, Fredrikson, Mats·2008·The Journal of Neuroscience

DOI 10.1523/jneurosci.2534-08.2008PMC PMC6671592

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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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Authors: Furmark, T., Appel, L., Henningsson, S., Åhs, F., Faria, V., Linnman, C., Pissiota, A., Frans, Ö., Bani, M., Bettica, P., Pich, E. M., Jacobsson, E., Wahlstedt, K., Oreland, L., Långström, B., Eriksson, E., & Fredrikson, M.
Affiliations: Uppsala University (SE)
University of Gothenburg (SE)
GlaxoSmithKline (Italy) (IT)
Corresponding author: Furmark, Tomas
ORCID: Furmark, Tomas
Appel, Lieuwe
Henningsson, Susanne
Åhs, Fredrik
Faria, Vanda
Linnman, Clas
Bani, Massimo
Bettica, Paolo
Pich, Emilio Merlo
Eriksson, Elias
Fredrikson, Mats
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2008-12-03
Volume: 28
Issue: 49
Pages: 13066-13074
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.2534-08.2008
PMC: PMC6671592
OpenAlex: W2161011520
Cited by: 210
References: 60
Citations by year: 2026: 1 · 2025: 8 · 2024: 1 · 2023: 3 · 2022: 10 · 2021: 8 · 2020: 14 · 2019: 5 · 2018: 11 · 2017: 13 · 2016: 17 · 2015: 14 · 2014: 25 · 2013: 15 · 2012: 18
FWCI: 7.82
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 182 d)
Locations: Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: GlaxoSmithKline
Vetenskapsrådet
Topics: Life Sciences › Neuroscience › Cognitive Neuroscience › Pain Management and Placebo Effect
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Social Sciences › Psychology › Experimental and Cognitive Psychology › Anxiety, Depression, Psychometrics, Treatment, Cognitive Processes
Keywords: placebo response, social anxiety disorder, serotonin, 5-HTTLPR, tryptophan hydroxylase 2, amygdala activity, genetic polymorphism, public speaking stress, serotonergic modulation
MeSH terms: Adult, Amygdala, Anxiety Disorders, DNA Mutational Analysis, Double-Blind Method, Female, Gene Frequency, Genetic Testing, Genotype, Humans, Male, Middle Aged, Neuropsychological Tests, Polymorphism, Genetic, Serotonin, Stress, Psychological, Tryptophan Hydroxylase, Placebo Effect, Genetic Predisposition to Disease, Positron-Emission Tomography, Serotonin Plasma Membrane Transport Proteins, Young Adult

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

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