The DOI matches its Crossref record; 59 of the 60 references it cites were found in a registry or an index.
A Link between Serotonin-Related Gene Polymorphisms, Amygdala Activity, and Placebo-Induced Relief from Social Anxiety
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The check wasn’t confident either way, so it gives no verdict — never disputed.
In the citing paper
“Elevated SLC6A4 methylation is also associated with generalized anxiety disorder (GAD) and panic disorder, correlates with increased anxiety traits, social anxiety, and amygdala hyperreactivity”
From The clinical use of epigenetics in psychiatry: a narrative review of epigenetic mechanisms, key candidate genes, and precision psychiatry (2025) · cites this paper as [107]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Diagnostic and Statistical Manual of Mental Disorders
Williams, J. B. W., & First, M. B. (2013) · Oxford University Press eBooks · doi:10.1093/acrefore/9780199975839.013.104 · Cited by 109,845
(1998) · The Journal of Clinical Psychiatry · Cited by 19,139
Co-Planar Stereotaxic Atlas of the Human Brain
Talairach, J., & Tournoux, P. (1988) · Medical Entomology and Zoology · Cited by 11,798
(1998) · PubMed · Cited by 10,216
Statistical parametric maps in functional imaging: A general linear approach
Friston, K. J., Holmes, A. P., Worsley, K. J., Poline, J. ‐., Frith, C. D., & Frackowiak, R. S. J. (1994) · Human Brain Mapping · doi:10.1002/hbm.460020402 · Cited by 9,688
The mini international neuropsychiatric interview
Lecrubier, Y., Sheehan, D. V., Hergueta, T., & Weiller, E. (1998) · European Psychiatry · doi:10.1016/s0924-9338(99)80239-9 · Cited by 5,899
Maldjian, J. A., Laurienti, P. J., Kraft, R., & Burdette, J. H. (2003) · NeuroImage · doi:10.1016/s1053-8119(03)00169-1 · Cited by 5,066
Mattick, R. P., & Clarke, J. C. (1998) · Behaviour Research and Therapy · doi:10.1016/s0005-7967(97)10031-6 · Cited by 3,367
Serotonin transporter genetic variation and the response of the human amygdala.
Hariri, A. R., Mattay, V. S., Tessitore, A., Kolachana, B., Fera, F., Goldman, D., Egan, M. F., & Weinberger, D. R. (2002) · Science · doi:10.1126/science.1071829 · Cited by 2,340
Liebowitz, M. R. (2015) · Modern Trends in Pharmacopsychiatry · doi:10.1159/000414022 · Cited by 2,266
Placebo-Induced Changes in fMRI in the Anticipation and Experience of Pain
Wager, T. D., Rilling, J. K., Smith, E. E., Sokolik, A., Casey, K. L., Davidson, R. J., Kosslyn, S. M., Rose, R. M., & Cohen, J. D. (2004) · Science · doi:10.1126/science.1093065 · Cited by 1,992
Beecher, H. K. (1955) · JAMA · doi:10.1001/jama.1955.02960340022006 · Cited by 1,850
Placebo and Opioid Analgesia-- Imaging a Shared Neuronal Network
Petrovic, P., Kalso, E., Petersson, K. M., & Ingvar, M. (2002) · Science · doi:10.1126/science.1067176 · Cited by 1,488
Jeurgen, K., Assheuer, J., & Paxinos, G. (1997) · Medical Entomology and Zoology · Cited by 1,403
Sheline, Y. I., Barch, D. M., Donnelly, J. M., Ollinger, J. M., Snyder, A. Z., & Mintun, M. A. (2001) · Biological Psychiatry · doi:10.1016/s0006-3223(01)01263-x · Cited by 1,191
Expectation and Dopamine Release: Mechanism of the Placebo Effect in Parkinson's Disease
de la Fuente‐Fernández, R., Ruth, T. J., Sossi, V., Schulzer, M., Calne, D. B., & Stoessl, A. J. (2001) · Science · doi:10.1126/science.1060937 · Cited by 991
Neurobiological Mechanisms of the Placebo Effect
Benedetti, F., Mayberg, H. S., Wager, T. D., Stohler, C. S., & Zubieta, J.-K. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.3458-05.2005 · Cited by 812
Placebo Effects Mediated by Endogenous Opioid Activity on μ-Opioid Receptors
Zubieta, J.-K., Bueller, J. A., Jackson, L. R., Scott, D. J., Xu, Y., Koeppe, R. A., Nichols, T. E., & Stohler, C. S. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.0439-05.2005 · Cited by 779
Fu, C. H. Y., Williams, S. C. R., Cleare, A. J., Brammer, M. J., Walsh, N. D., Kim, J., Andrew, C. M., Pich, E. M., Williams, P. M., Reed, L. J., et al. (2004) · Archives of General Psychiatry · doi:10.1001/archpsyc.61.9.877 · Cited by 775
Self-citationThe Functional Neuroanatomy of the Placebo Effect
Mayberg, H. S., Silva, J. A., Brannan, S., Tekell, J. L., Mahurin, R. K., McGinnis, S. M., & Jerabek, P. A. (2002) · American Journal of Psychiatry · doi:10.1176/appi.ajp.159.5.728 · Cited by 731
Genetics of emotional regulation: the role of the serotonin transporter in neural function
Hariri, A. R., & Holmes, A. (2006) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2006.02.011 · Cited by 688
Increased Amygdala Activation to Angry and Contemptuous Faces in Generalized Social Phobia
Stein, M. B., Goldin, P. R., Sareen, J., Zorrilla, L. T. E., & Brown, G. G. (2002) · Archives of General Psychiatry · doi:10.1001/archpsyc.59.11.1027 · Cited by 598
Placebo effects on human μ-opioid activity during pain
Wager, T. D., Scott, D. J., & Zubieta, J.-K. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0702413104 · Cited by 562
Phan, K. L., Fitzgerald, D. A., Nathan, P. J., & Tancer, M. E. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.08.012 · Cited by 539
Furmark, T., Tillfors, M., Marteinsdottir, I., Fischer, H., Pissiota, A., Långström, B., & Fredrikson, M. (2002) · Archives of General Psychiatry · doi:10.1001/archpsyc.59.5.425 · Cited by 530
Self-citationIndividual differences in reward responding explain placebo-induced expectations and effects
Scott, D. J., Stohler, C. S., Egnatuk, C. M., Wang, H., Koeppe, R. A., & Zubieta, J.-K. (2007) · Neuron · doi:10.1016/j.neuron.2007.06.028 · Cited by 466
Antidepressant Drug Treatment Modifies the Neural Processing of Nonconscious Threat Cues
Harmer, C. J., Mackay, C. E., Reid, C. B., Cowen, P. J., & Goodwin, G. M. (2006) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.10.015 · Cited by 450
Gelernter, J., Kranzler, H., & Cubells, J. (1997) · Human Genetics · doi:10.1007/s004390050624 · Cited by 448
Petrovic, P., Dietrich, T., Fransson, P., Andersson, J., Carlsson, K., & Ingvar, M. (2005) · Neuron · doi:10.1016/j.neuron.2005.05.023 · Cited by 437 · cited 4×
“The present results are consistent with the notion that placebo and active pharmacological agents act on the same, or at least overlapping, neural pathways (Mayberg et al., 2002; Petrovic et al., 2002, 2005; Benedetti et al., 2005; Faria et al., 2008).”
BackgroundMethodResultInfluentialSmolka, M. N., Schumann, G., Wrase, J., Grüsser, S. M., Flor, H., Mann, K. F., Braus, D. F., Goldman, D. A., Büchel, C., & Heinz, A. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.1792-04.2005 · Cited by 422
Cerebral Blood Flow in Subjects With Social Phobia During Stressful Speaking Tasks: A PET Study
Tillfors, M., Furmark, T., Marteinsdóttir, Í., Fischer, H., Pissiota, A., Långström, B., & Fredrikson, M. G. (2001) · American Journal of Psychiatry · doi:10.1176/appi.ajp.158.8.1220 · Cited by 357
Self-citationPaulus, M. P., Feinstein, J. S., Castillo, G., Simmons, A. N., & Stein, M. B. (2005) · Archives of General Psychiatry · doi:10.1001/archpsyc.62.3.282 · Cited by 314
Evaluation of the Clinical Global Impression Scale among individuals with social anxiety disorder
ZAIDER, T. I., HEIMBERG, R. G., FRESCO, D. M., SCHNEIER, F. R., & LIEBOWITZ, M. R. (2003) · Psychological Medicine · doi:10.1017/s0033291703007414 · Cited by 286
(2004) · PubMed · Cited by 272
A regulatory variant of the human tryptophan hydroxylase-2 gene biases amygdala reactivity
Brown, S. M., Peet, E., Manuck, S. B., Williamson, D. E., Dahl, R. E., Ferrell, R. E., & Hariri, A. R. (2005) · Molecular Psychiatry · doi:10.1038/sj.mp.4001716 · Cited by 241
Furmark, T., Tillfors, M., Garpenstrand, H., Marteinsdóttir, Í., Långström, B., Oreland, L., & Fredrikson, M. (2004) · Neuroscience Letters · doi:10.1016/j.neulet.2004.02.070 · Cited by 234
Self-citationCerebral blood flow during anticipation of public speaking in social phobia: a PET study
Tillfors, M., Furmark, T., Marteinsdóttir, Í., & Fredrikson, M. (2002) · Biological Psychiatry · doi:10.1016/s0006-3223(02)01396-3 · Cited by 230
Self-citationSerotonin Transporter Gene Variants and Behavior: A Comprehensive Review
Serretti, A., Calati, R., Mandelli, L., & Ronchi, D. D. (2006) · Current Drug Targets · doi:10.2174/138945006779025419 · Cited by 224
Whalen, P. J., Johnstone, T., Somerville, L. H., Nitschke, J. B., Polis, S., Alexander, A. L., Davidson, R. J., & Kalin, N. H. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.08.019 · Cited by 217
Furmark, T., Appel, L., Michelgård, Å., Wahlstedt, K., Åhs, F., Zancan, S., Jacobsson, E., Flyckt, K., Grohp, M., Bergström, M., et al. (2005) · Biological Psychiatry · doi:10.1016/j.biopsych.2005.03.029 · Cited by 208
Self-citationEscitalopram effects on insula and amygdala BOLD activation during emotional processing
Arce, E., Simmons, A. N., Lovero, K. L., Stein, M. B., & Paulus, M. P. (2008) · Psychopharmacology · doi:10.1007/s00213-007-1004-8 · Cited by 198
Rausch, J. L., Johnson, M. E., Fei, Y.-J., Li, J. Q., Shendarkar, N., Hobby, H. M., Ganapathy, V., & Leibach, F. H. (2002) · Biological Psychiatry · doi:10.1016/s0006-3223(01)01283-5 · Cited by 193
Amygdala responsiveness is modulated by tryptophan hydroxylase-2 gene variation
Canli, T., Congdon, E., Gutknecht, L., Constable, R. T., & Lesch, K. P. (2005) · Journal of Neural Transmission · doi:10.1007/s00702-005-0391-4 · Cited by 188
Acute 5-HT Reuptake Blockade Potentiates Human Amygdala Reactivity
Bigos, K. L., Pollock, B. G., Aizenstein, H. J., Fisher, P. M., Bies, R. R., & Hariri, A. R. (2008) · Neuropsychopharmacology · doi:10.1038/npp.2008.52 · Cited by 164
Stein, M. B., Seedat, S., & Gelernter, J. E. (2006) · Psychopharmacology · doi:10.1007/s00213-006-0349-8 · Cited by 161
Capacity for 5-HT1A–mediated autoregulation predicts amygdala reactivity
Fisher, P. M., Meltzer, C. C., Ziolko, S. K., Price, J. C., Moses-Kolko, E. L., Berga, S. L., & Hariri, A. R. (2006) · Nature Neuroscience · doi:10.1038/nn1780 · Cited by 156
Amygdala Hyperfunction in Phobic Fear Normalizes After Exposure
Goossens, L., Sunaert, S. G., Peeters, R. R., Griez, E. J. L., & Schruers, K. R. J. (2007) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.04.024 · Cited by 146
PERES, J. F. P., Newberg, A. B., Mercante, J. P. P., Simão, M. J. P., ALBUQUERQUE, V. E., PERES, M. J. P., & Nasello, A. G. (2007) · Psychological Medicine · doi:10.1017/s003329170700997x · Cited by 142
Serotonergic genes modulate amygdala activity in major depression
Dannlowski, U., Ohrmann, P., Bauer, J., Kugel, H., Baune, B. T., Hohoff, C., Kersting, A., Arolt, V., Heindel, W. L., Deckert, J., et al. (2006) · Genes Brain & Behavior · doi:10.1111/j.1601-183x.2006.00297.x · Cited by 127
Which Factors Predict Placebo Response in Anxiety Disorders and Major Depression?
Stein, D. J., Baldwin, D. S., Dolberg, O. T., Despiégel, N., & Bandelow, B. (2006) · The Journal of Clinical Psychiatry · doi:10.4088/jcp.v67n1111 · Cited by 121
Herrmann, M. J., Huter, T. J., Müller, F. U., Mühlberger, A., Pauli, P., Reif, A., Renner, T., Canli, T., Fallgatter, A. J., & Lesch, K. (2006) · Cerebral Cortex · doi:10.1093/cercor/bhl026 · Cited by 100
Human 5-HT Transporter Availability Predicts Amygdala Reactivity In Vivo
Rhodes, R. A., Murthy, N. V., Dresner, M. A., Selvaraj, S., Stavrakakis, N., Babar, S., Cowen, P. J., & Grasby, P. M. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.1175-07.2007 · Cited by 93
Canli, T., Congdon, E., Todd Constable, R., & Lesch, K. P. (2008) · Biological Psychology · doi:10.1016/j.biopsycho.2008.01.004 · Cited by 89
Imaging the placebo response: A neurofunctional review
Faria, V., Fredrikson, M. G., & Furmark, T. (2008) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2008.03.002 · Cited by 68
Self-citationCrossing cultural divides: moral conflict and the Cairo population conference.
Davis, J. E. (1995) · PubMed · Cited by 65
Bauman, M. D., & Amaral, D. G. (2005) · Neuroscience · doi:10.1016/j.neuroscience.2005.07.040 · Cited by 59
Lorazepam dose-dependently decreases risk-taking related activation in limbic areas
Arce, E., Miller, D. A., Feinstein, J. S., Stein, M. B., & Paulus, M. P. (2006) · Psychopharmacology · doi:10.1007/s00213-006-0519-8 · Cited by 44
The role of the endogenous opioid system in the pathogenesis of anxiety disorders
Sher, L. (1998) · Medical Hypotheses · doi:10.1016/s0306-9877(98)90264-x · Cited by 27
Lurito (2000) · doi:10.1002/1097-0193(200007)10:3
Research works printed but not linked: 1
- Raftery AE (1993) in Testing structural equation models, Bayesian model selection in structural equation models, eds Bollen KA Long JS (Sage Publications, Newbury Park, CA), pp 163–180.
Cited by
Sorted by citations
Biological, clinical, and ethical advances of placebo effects
Finniss, D. G., Kaptchuk, T. J., Miller, F. G., & Benedetti, F. (2010) · The Lancet · doi:10.1016/s0140-6736(09)61706-2 · Cited by 1,309
The placebo response in medicine: minimize, maximize or personalize?
Enck, P., Bingel, U., Schedlowski, M., & Rief, W. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd3923 · Cited by 671
Placebo and the New Physiology of the Doctor-Patient Relationship
Benedetti, F. (2013) · Physiological Reviews · doi:10.1152/physrev.00043.2012 · Cited by 492
How Placebos Change the Patient's Brain
Benedetti, F., Carlino, E., & Pollo, A. (2011) · Neuropsychopharmacology · doi:10.1038/npp.2010.81 · Cited by 446
Schedlowski, M., Enck, P., Rief, W., & Bingel, U. (2015) · Pharmacological Reviews · doi:10.1124/pr.114.009423 · Cited by 323
Metadata
- 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
- 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
- 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
- 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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
