Trial reportThe Journal of neuroscience : the official journal of the Society for Neuroscience2008
A link between serotonin-related gene polymorphisms, amygdala activity, and placebo-induced relief from social anxiety.
Trial report in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 5 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
66 citing papers in PubMed, 5 syntheses or guidelines pooled it, 209 citations in OpenAlex.
- Role of expectations in clinical outcomes after deep brain stimulation in patients with Parkinson's disease: a systematic review.Journal of neurology · 2023Pooled it
- Functional Neuroimaging Correlates of Placebo Response in Patients With Depressive or Anxiety Disorders: A Systematic Review.The international journal of neuropsychopharmacology · 2022Pooled it
- Placebo eff ects in psychiatry: mediators and moderators.The lancet. Psychiatry · 2015Pooled it
- Placebo Responses in Genetically Determined Intellectual Disability: A Meta-Analysis.PloS one · 2015Pooled it
- The effect of the serotonin transporter polymorphism (5-HTTLPR) on amygdala function: a meta-analysis.Molecular psychiatry · 2013Pooled it
- Association of catechol-O-methyltransferase genetic polymorphism with neuromodulation treatment response in women with fecal or urinary incontinence.American journal of obstetrics and gynecology · 2025Trial
- Alpha-Glycerylphosphorylcholine Increases Motivation in Healthy Volunteers: A Single-Blind, Randomized, Placebo-Controlled Human Study.Nutrients · 2021Trial
- A double-blind, placebo-controlled trial on the antihypertensive treatment effect of a quadruple single-pill combination.Journal of clinical hypertension (Greenwich, Conn.) · 2021Trial
- Do You Believe It? Verbal Suggestions Influence the Clinical and Neural Effects of Escitalopram in Social Anxiety Disorder: A Randomized Trial.EBioMedicine · 2017Trial
- Trial
- Network modulation following sham surgery in Parkinson's disease.The Journal of clinical investigation · 2014Trial
- Genetic polymorphisms in monoamine systems and outcome of cognitive behavior therapy for social anxiety disorder.PloS one · 2013Trial
- Neural response to eye contact and paroxetine treatment in generalized social anxiety disorder.Psychiatry research · 2011Trial
- Serum correlates of the placebo effect in irritable bowel syndrome.Neurogastroenterology and motility · 2010Trial
- "Maybe I made up the whole thing": placebos and patients' experiences in a randomized controlled trial.Culture, medicine and psychiatry · 2009Trial
- The clinical use of epigenetics in psychiatry: a narrative review of epigenetic mechanisms, key candidate genes, and precision psychiatry.Frontiers in psychiatry · 2025Review
- Revisiting the SSRI vs. placebo debate in the treatment of social anxiety disorder: the role of expectancy effects, neural responsivity, and monoamine transporters.Frontiers in psychology · 2025Article
- Placebo: a brief updated review.Naunyn-Schmiedeberg's archives of pharmacology · 2022Review
- Functional neurological disorder and placebo and nocebo effects: shared mechanisms.Nature reviews. Neurology · 2022Review
- Effects of Open-Label Placebos on State Anxiety and Glucocorticoid Stress Responses.Brain sciences · 2021Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
17 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
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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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.