Contribution of oxytocin receptor polymorphisms to amygdala activation in schizophrenia spectrum disorders
Open accessAbstract
BACKGROUND: Oxytocin has been proposed to mediate amygdala dysfunction associated with altered emotion processing in schizophrenia, but the contribution of oxytocin pathway genes is yet to be investigated. AIMS: To identify potential different contributions of three oxytocin receptor polymorphisms (rs53576, rs237902 and rs2254298) between patients with schizophrenia spectrum disorders (SCZ), affective spectrum disorders (AD) and healthy controls (HC). METHOD: In a total of 346 participants (104 with SCZ, 100 with AD, and 142 HC) underwent genotyping and functional magnetic resonance imaging (fMRI) during an emotional faces matching paradigm. Genetic association analyses were performed to test the possible effects on task-induced BOLD amygdala response to fearful/angry faces. RESULTS: =0.03). There were no associations between oxytocin polymorphisms and amygdala activation in the total sample, among AD patients or HC. CONCLUSIONS: Rs237902 was associated with amygdala activation in response to fearful/angry faces only in patients with SCZ. Our findings indicate that the endogenous oxytocin system could serve as a contributing factor in biological underpinnings of emotion processing and that this contribution is disorder specific. DECLARATION OF INTEREST: O.A.A. received speaker's honoraria from GSK, Otsuka, Lundbeck. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2016. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) licence.
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
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?
In humans, alterations in amygdala responses to positive and negative emotions have been reported in neuropsychiatric conditions such as autism and schizophrenia, in association with OXTR genetic variants or following intranasal OXT.
“In humans, alterations in amygdala responses to positive and negative emotions have been reported in neuropsychiatric conditions, such as autism and schizophrenia [72,73], in association with OXTR genetic variants [41,102] or following intranasal OXT [33,36,38,103].”
From Oxytocin Signaling in the Central Amygdala Modulates Emotion Discrimination in Mice (2019) · cites this paper as [102]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Advances in functional and structural MR image analysis and implementation as FSL
Smith, S. M., Jenkinson, M., Woolrich, M. W., Beckmann, C. F., Behrens, T. E. J., Johansen-Berg, H., Bannister, P. R., De Luca, M., Drobnjak, I., Flitney, D. E., et al. (2004) · NeuroImage · doi:10.1016/j.neuroimage.2004.07.051 · Cited by 13,630 · see citing works
Jenkinson, M., Bannister, P., Brady, M., & Smith, S. (2002) · NeuroImage · doi:10.1006/nimg.2002.1132 · Cited by 11,888 · see citing works
Fast robust automated brain extraction
Smith, S. M. (2002) · Human Brain Mapping · doi:10.1002/hbm.10062 · Cited by 10,496 · see citing works
The NimStim set of facial expressions: Judgments from untrained research participants.
Tottenham, N., Tanaka, J. W., Leon, A. C., McCarry, T., Nurse, M., Hare, T. A., Marcus, D. J., Westerlund, A., Casey, B., & Nelson, C. (2009) · Psychiatry Research · doi:10.1016/j.psychres.2008.05.006 · Cited by 3,454 · see citing works
SUSAN—a new approach to low level image processing
Smith, S. M., & Brady, J. M. (1997) · International Journal of Computer Vision · doi:10.1023/a:1007963824710 · Cited by 3,333 · see citing works
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 · see citing works
Social effects of oxytocin in humans: context and person matter
Bartz, J. A., Zaki, J., Bolger, N., & Ochsner, K. N. (2011) · Trends in Cognitive Sciences · doi:10.1016/j.tics.2011.05.002 · Cited by 1,572 · cited 1× · see citing works
“3,4 7 The results from oxytocin trials are inconsistent in general, 3,4,8 and this inconsistency has been attributed to individual differences, including genetically based differences in the oxytocin system, 9,10 and a poor understanding of drug targets and mechanisms.”
Social cognition in schizophrenia
Green, M. F., Horan, W. P., & Lee, J. (2015) · Nature Reviews Neuroscience · doi:10.1038/nrn4005 · Cited by 1,159 · see citing works
The human amygdala and the emotional evaluation of sensory stimuli
Zald, D. H. (2003) · Brain Research Reviews · doi:10.1016/s0165-0173(02)00248-5 · Cited by 1,062 · see citing works
Insel, T. R. (2010) · Neuron · doi:10.1016/j.neuron.2010.03.005 · Cited by 1,044 · see citing works
Understanding the contribution of synonymous mutations to human disease
Sauna, Z. E., & Kimchi-Sarfaty, C. (2011) · Nature Reviews Genetics · doi:10.1038/nrg3051 · Cited by 1,022 · see citing works
The Social Salience Hypothesis of Oxytocin
Shamay-Tsoory, S. G., & Abu-Akel, A. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.07.020 · Cited by 904 · cited 2× · see citing works
“5 Additionally, several brain imaging studies investigating oxytocin pathway genes in healthy individuals have detected sex-specific effects.”
Korn, J. M., Kuruvilla, F. G., McCarroll, S. A., Wysoker, A., Nemesh, J., Cawley, S., Hubbell, E., Veitch, J., Collins, P. J., Darvishi, K., et al. (2008) · Nature Genetics · doi:10.1038/ng.237 · Cited by 783 · see citing works
Facial Emotion Recognition in Schizophrenia: Intensity Effects and Error Pattern
Kohler, C. G., Turner, T. H., Bilker, W. B., Brensinger, C. M., Siegel, S. J., Kanes, S., Gur, R. E., & Gur, R. C. (2003) · American Journal of Psychiatry · doi:10.1176/appi.ajp.160.10.1768 · Cited by 782 · see citing works
Costafreda, S. G., Brammer, M. J., David, A. S., & Fu, C. H. Y. (2008) · Brain Research Reviews · doi:10.1016/j.brainresrev.2007.10.012 · Cited by 772 · see citing works
Intranasal Oxytocin: Myths and Delusions
Leng, G., & Ludwig, M. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.05.003 · Cited by 615 · cited 1× · see citing works
“11 15 The endogenous oxytocin system is less explored, and the contribution of oxytocin path ‐ way genes to amygdala activation has yet to be investigated in this patient group.”
Tost, H., Kolachana, B., Hakimi, S., Lemaitre, H., Verchinski, B. A., Mattay, V. S., Weinberger, D. R., & Meyer–Lindenberg, A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1003296107 · Cited by 564 · see citing works
Effects of intranasal oxytocin on emotional face processing in women
Domes, G., Lischke, A., Berger, C., Grossmann, A., Hauenstein, K., Heinrichs, M., & Herpertz, S. C. (2010) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2009.06.016 · Cited by 521 · cited 1× · see citing works
“3,4 7 The results from oxytocin trials are inconsistent in general, 3,4,8 and this inconsistency has been attributed to individual differences, including genetically based differences in the oxytocin system, 9,10 and a poor understanding of drug targets and mechanisms.”
Dumais, K. M., & Veenema, A. H. (2016) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2015.04.003 · Cited by 520 · cited 1× · see citing works
“45 The expression of central oxytocin is steroid-SCZ dependent, 46 the central regulation differs between men and women, 47 and men and women respond differently to exogenous oxytocin.”
Feldman, R., Monakhov, M., Pratt, M., & Ebstein, R. P. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.08.008 · Cited by 352 · see citing works
The oxytocin receptor gene (OXTR) is associated with autism spectrum disorder: a meta-analysis
LoParo, D., & Waldman, I. D. (2015) · Molecular Psychiatry · doi:10.1038/mp.2014.77 · Cited by 343 · see citing works
Rilling, J. K., DeMarco, A. C., Hackett, P. D., Chen, X., Gautam, P., Stair, S., Haroon, E., Thompson, R., Ditzen, B., Patel, R., et al. (2014) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2013.09.022 · Cited by 343 · see citing works
Taylor, S. F., Kang, J., Brege, I. S., Tso, I. F., Hosanagar, A., & Johnson, T. D. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.09.007 · Cited by 341 · see citing works
Facial emotion processing in schizophrenia: a meta-analysis of functional neuroimaging data.
Li, H., Chan, R., McAlonan, G., & Gong, Q. (2010) · Schizophrenia bulletin · doi:10.1093/schbul/sbn190 · Cited by 331 · see citing works
Bethlehem, R. A. I., van Honk, J., Auyeung, B., & Baron-Cohen, S. (2013) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2012.10.011 · Cited by 285 · see citing works
Anticevic, A., Snellenberg, J. X. V., Cohen, R. E., Repovš, G., Dowd, E. C., & Barch, D. M. (2010) · Schizophrenia Bulletin · doi:10.1093/schbul/sbq131 · Cited by 248 · see citing works
A sociability gene? Meta-analysis of oxytocin receptor genotype effects in humans
Bakermans‐Kranenburg, M. J., & van IJzendoorn, M. H. (2013) · Psychiatric Genetics · doi:10.1097/ypg.0b013e3283643684 · Cited by 217 · see citing works
Athanasiu, L., Mattingsdal, M., Kähler, A. K., Brown, A. A., Gústafsson, Ó., Agartz, I., Giegling, I., Muglia, P., Cichon, S., Rietschel, M., et al. (2010) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2010.02.002 · Cited by 210 · see citing works
Overactivation of Fear Systems to Neutral Faces in Schizophrenia
Hall, J., Whalley, H. C., McKirdy, J. W., Romaniuk, L., McGonigle, D. J., McIntosh, A. M., Baig, B. J., Gountouna, V., Job, D. E., Donaldson, D. I., et al. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.12.014 · Cited by 195 · see citing works
Association of Oxytocin Receptor Gene (OXTR) rs53576 Polymorphism with Sociality: A Meta-Analysis
Li, J., Zhao, Y., Li, R., Broster, L. S., Zhou, C., & Yang, S. (2015) · PLoS ONE · doi:10.1371/journal.pone.0131820 · Cited by 168 · see citing works
Corcoran, C. M., Keilp, J. G., Jürgen Kayser, A., Klim, C. C., Butler, P. D., Bruder, G. E., Gur, R. C., & Javitt, D. C. (2015) · Psychological Medicine · doi:10.1017/s0033291715000902 · Cited by 135 · see citing works
Montag, C., Brockmann, E.-M., Lehmann, A. I., Müller, D. J., Rujescu, D., & Gallinat, J. (2012) · PLoS ONE · doi:10.1371/journal.pone.0051882 · Cited by 123 · see citing works
Djurovic, S., Gústafsson, Ó., Mattingsdal, M., Athanasiu, L., Bjella, T. D., Tesli, M., Agartz, I., Lorentzen, S., Melle, I. S., Morken, G., et al. (2010) · Journal of Affective Disorders · doi:10.1016/j.jad.2010.04.007 · Cited by 120 · see citing works
Ventura, J., Wood, R. C., Jimenez, A. M., & Hellemann, G. (2013) · Schizophrenia Research · doi:10.1016/j.schres.2013.10.015 · Cited by 114 · see citing works
A Review of Oxytocin’s Effects on the Positive, Negative, and Cognitive Domains of Schizophrenia
Feifel, D., Shilling, P. D., & MacDonald, K. (2016) · Biological Psychiatry · doi:10.1016/j.biopsych.2015.07.025 · Cited by 110 · see citing works
Oxytocin and oxytocin receptor gene polymorphisms and risk for schizophrenia: A case–control study
Montag, C., Brockmann, E.-M., Bayerl, M., Rujescu, D., Müller, D. J., & Gallinat, J. (2012) · The World Journal of Biological Psychiatry · doi:10.3109/15622975.2012.677547 · Cited by 104 · see citing works
Carré, J. M., Fisher, P. M., Manuck, S. B., & Hariri, A. R. (2010) · Social Cognitive and Affective Neuroscience · doi:10.1093/scan/nsq101 · Cited by 96 · see citing works
Sex hormones and oxytocin augmentation strategies in schizophrenia: A quantitative review
Heringa, S. M., Begemann, M., Goverde, A. J., & Sommer, I. E. (2015) · Schizophrenia Research · doi:10.1016/j.schres.2015.04.002 · Cited by 82 · see citing works
Potential of Oxytocin in the Treatment of Schizophrenia
Shilling, P. D., & Feifel, D. (2016) · CNS Drugs · doi:10.1007/s40263-016-0315-x · Cited by 82 · see citing works
Neurogenetic effects of OXTR rs2254298 in the extended limbic system of healthy Caucasian adults
Tost, H., Kolachana, B., Verchinski, B. A., Bilek, E., Goldman, A. L., Mattay, V. S., Weinberger, D. R., & Meyer-Lindenberg, A. (2011) · Biological Psychiatry · doi:10.1016/j.biopsych.2011.06.034 · Cited by 77 · see citing works
Neural mechanisms of oxytocin receptor gene mediating anxiety-related temperament
Wang, J., Qin, W., Liu, B., Zhou, Y., Wang, D., Zhang, Y., Jiang, T., & Yu, C. (2013) · Brain Structure and Function · doi:10.1007/s00429-013-0584-9 · Cited by 77 · see citing works
Uhrig, S., Hirth, N., Broccoli, L., von Wilmsdorff, M., Bauer, M., Sommer, C., Zink, M., Steiner, J. H., Frodl, T., Malchow, B., et al. (2016) · Schizophrenia Research · doi:10.1016/j.schres.2016.04.019 · Cited by 75 · see citing works
Effects of Oxytocin on Neural Response to Facial Expressions in Patients with Schizophrenia
Shin, N. Y., Park, H. Y., Jung, W. H., Park, J. W., Yun, J., Jang, J. H., Kim, S. N., Han, H. J., Kim, S.-Y., Kang, D., et al. (2015) · Neuropsychopharmacology · doi:10.1038/npp.2015.41 · Cited by 69 · see citing works
Loth, E., Poline, J.-B., Thyreau, B., Jia, T., Tao, C., Lourdusamy, A., Stacey, D., Cattrell, A., Desrivières, S., Ruggeri, B., et al. (2014) · Biological Psychiatry · doi:10.1016/j.biopsych.2013.07.043 · Cited by 65 · see citing works
Tesli, M., Kauppi, K., Bettella, F., Brandt, C. L., Kaufmann, T., Espeseth, T., Mattingsdal, M., Agartz, I., Melle, I. S., Djurovic, S., et al. (2015) · PLoS ONE · doi:10.1371/journal.pone.0134202 · Cited by 62 · see citing works
Bartholomeusz, C. F., Ganella, E. P., Labuschagne, I., Bousman, C., & Pantelis, C. (2015) · Schizophrenia Research · doi:10.1016/j.schres.2015.06.007 · Cited by 54 · see citing works
Haram, M., Tesli, M., Bettella, F., Djurovic, S., Andreassen, O. A., & Melle, I. S. (2015) · Frontiers in Human Neuroscience · doi:10.3389/fnhum.2015.00009 · Cited by 42 · see citing works
Variant in OXTR gene and functional connectivity of the hypothalamus in normal subjects
Wang, J., Qin, W., Liu, B., Wang, D., Zhang, Y., Jiang, T., & Yu, C. (2013) · NeuroImage · doi:10.1016/j.neuroimage.2013.05.029 · Cited by 42 · see citing works
Replication in Imaging Genetics: The Case of Threat-Related Amygdala Reactivity
Avinun, R., Nevo, A., Knodt, A. R., Elliott, M. L., & Hariri, A. R. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.11.010 · Cited by 26 · see citing works
Ousdal, O. T., Brown, A. A., Jensen, J., Nakstad, P., Melle, I. S., Agartz, I., Djurovic, S., Bogdan, R., Hariri, A. R., & Andreassen, O. A. (2012) · Twin Research and Human Genetics · doi:10.1017/thg.2012.5 · Cited by 25 · see citing works
Buckley, P. F., Friedman, L., Wu, D., Lai, S., Meltzer, H. Y., Miller, D., Haacke, E. M., & Lewin, J. S. (1995) · Schizophrenia Research · doi:10.1016/0920-9964(95)95244-4 · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Oxytocin Signaling in the Central Amygdala Modulates Emotion Discrimination in Mice
Ferretti, V., Maltese, F., Contarini, G., Nigro, M., Bonavia, A., Huang, H., Gigliucci, V., Morelli, G., Scheggia, D., Managò, F., et al. (2019) · Current Biology · doi:10.1016/j.cub.2019.04.070 · Cited by 212 · see citing works
Oxytocin and vasopressin: signalling, behavioural modulation and potential therapeutic effects
Rae, M., Lemos Duarte, M., Gomes, I., Camarini, R., & Devi, L. A. (2022) · British Journal of Pharmacology · doi:10.1111/bph.15481 · Cited by 72 · see citing works
Quintana, D. S., Dieset, I., Elvsåshagen, T., Westlye, L. T., & Andreassen, O. A. (2017) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2016.12.004 · Cited by 39 · see citing works
Replication in Imaging Genetics: The Case of Threat-Related Amygdala Reactivity
Avinun, R., Nevo, A., Knodt, A. R., Elliott, M. L., & Hariri, A. R. (2017) · Biological Psychiatry · doi:10.1016/j.biopsych.2017.11.010 · Cited by 26 · see citing works
Ocakoğlu, F. T., Köse, S., Özbaran, B., & Onay, H. (2018) · Asian Journal of Psychiatry · doi:10.1016/j.ajp.2018.01.002 · Cited by 23 · see citing works
Chapter 4. Psychoneuroendocrinology
Sforzini, L., Weston, F. I., & Pariante, C. M. (2024) · American Psychiatric Association Publishing eBooks · doi:10.1176/appi.books.9781615375523.as04 · Cited by 16 · see citing works
Qin, Y., Kang, J., Jiao, Z., Wang, Y., Wang, J., Wang, H., Feng, J., Li, J., Wang, F., & Gong, X. (2020) · Translational Psychiatry · doi:10.1038/s41398-020-01001-2 · Cited by 16 · see citing works
Veras, A. B., Getz, M., Froemke, R. C., Nardi, A. E., Alves, G. S., Walsh‐Messinger, J., Chao, M. V., Kranz, T. M., & Malaspina, D. (2017) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2017.11.011 · Cited by 14 · see citing works
Zazueta, A., Castillo, T., Álvaro Cavieres, F., Gonzalez, R. C., Abarca, M., Nieto, R. R., Deneken, J., Araneda, C., Moya, P. R., & Bustamante, M. L. (2022) · The International Journal of Neuropsychopharmacology · doi:10.1093/ijnp/pyac025 · Cited by 12 · see citing works
Connectome dysfunction in patients at clinical high risk for psychosis and modulation by oxytocin
Davies, C., Martins, D., Dipasquale, O., McCutcheon, R. A., Micheli, A. D., Ramella‐Cravaro, V., Provenzani, U., Rutigliano, G., Cappucciati, M., Oliver, D., et al. (2024) · Molecular Psychiatry · doi:10.1038/s41380-024-02406-x · Cited by 9 · see citing works
Pałasz, A., Pałka, M., Filipczyk, Ł., Menezes, I. C., Rojczyk, E., Worthington, J. J., Piwowarczyk-Nowak, A., Krzystanek, M., & Wiaderkiewicz, R. (2018) · Journal of Neural Transmission · doi:10.1007/s00702-018-1868-2 · Cited by 10 · see citing works
Neuroimaging genetics of oxytocin: A transcriptomics-informed systematic review
Prata, D. P., & Silva, M. (2022) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2022.104912 · Cited by 7 · see citing works
- Authors
- Haram, M., Bettella, F., Brandt, C. L., Quintana, D. S., Nerhus, M., Bjella, T., Djurovic, S., Westlye, L. T., Andreassen, O. A., Melle, I., & Tesli, M.
- Affiliations
- Oslo University Hospital (NO)
- Corresponding author
- Haram, Marit
- ORCID
- Venue
- BJPsych Open
- Publisher
- Royal College of Psychiatrists
- Published
- 2016-11
- Volume
- 2
- Issue
- 6
- Pages
- 353-358
- ISSN
- 2056-4724 (ISSN-L)
- PMC
- PMC5099986
- OpenAlex
- W2546937281
- Cited by
- 13
- References
- 51
- Citations by year
- 2024: 2 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 2 · 2017: 3
- FWCI
- 3.14
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- BJPsych Open (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- NORA - Norwegian Open Research Archives (submittedVersion, cc-by-nc-nd)
- Funders
- Stiftelsen Kristian Gerhard Jebsen
- Universitetet i Oslo
- Norges Forskningsråd (#167153/V50, 147787, 181831, 204966, #204966/F20, 147787/320, 167153, 167153/V50, 204966/F20)
- Lovisenberg Diakonale Sykehus
- H. Lundbeck A/S
- Topics
- Social Sciences › Psychology › Social Psychology › Neuroendocrine regulation and behavior
- Health Sciences › Medicine › Psychiatry and Mental health › Schizophrenia research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- oxytocin receptor, OXTR polymorphisms, rs53576, rs2254298, amygdala activation, schizophrenia spectrum disorders, affective spectrum disorders, emotional processing, fearful faces, angry faces, genetic association
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
