COMT genotype is associated with plasticity in sense of body ownership: a pilot study

  • Motoyasu Honma
  • Takuya Yoshiike
  • Hiroki Ikeda
  • Kenichi Kuriyama
Original Article


The sense of body ownership constantly adapts to new environments, and awareness of a distinction between oneself and others is a fundamental ability. However, it remains unclear whether plasticity in the sense of body ownership is dependent on genetic factors. The present study investigated the influence of the catechol-O-methyltransferase (COMT) Val158Met genotype on illusory learning of a sense of body ownership and dissociation. 76 healthy Japanese participants experienced the rubber hand illusion (RHI), which is produced by sensory integration of conflicting modalities, with the intent to experimentally alter objective perceived locations and subjective ownership ratings. We found that Val/Val homozygous participants had more intense RHI experiences than Val/Met heterozygous and Met homozygous participants. Furthermore, RHI sensation was correlated with a dissociative personality trait in Val/Val homozygous participants. Our findings indicate an interaction between COMT genotype, RHI sensation, and dissociative personality traits: Val/Val genotypes were associated with RHI induction and greater vulnerability to dissociation. The findings suggest that Val/Val homozygous individuals may be more flexible regarding self-attribution/body ownership and that biological factors may contribute to reduced awareness regarding the distinction between self and others.


Body ownership Plasticity Rubber hand illusion COMT genotype Dissociative personality trait 



This work was supported by Grants-in-Aid for Scientific research (#24650142 and #15H04897) from the Japan Science and Technology (JST) Corporation, the Japan Foundation for Neuroscience and Mental Health, the Takeda Science Foundation, and the SENSHIN Medical Research Foundation. We thank Sayori Koyama, Miyuki Shimazaki, and Mikiko Kimura for assistance with the experiment.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the National Center of Neurology and Psychiatry committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.


  1. Albrecht, M. A., Martin-Iverson, M. T., Price, G., Lee, J., Iyyalol, R., & Waters, F. (2011). Dexamphetamine effects on separate constructs in the rubber hand illusion test. Psychopharmacology, 217(1), 39–50.CrossRefPubMedGoogle Scholar
  2. Alexander, G. E., & Crutcher, M. D. (1990). Functional architecture of basal ganglia circuits: Neural substrates of parallel processing. Trends in Neurosciences, 13(7), 266–271.CrossRefPubMedGoogle Scholar
  3. Armel, K. C., & Ramachandran, V. S. (2003). Projecting sensations to external objects: Evidence from skin conductance response. Proceedings of the Royal Society B, Biological sciences, 270(1523), 1499–1506.CrossRefPubMedPubMedCentralGoogle Scholar
  4. Asai, T., Mao, Z., Sugimori, E., & Tanno, Y. (2011). Rubber hand illusion, empathy, and schizotypal experiences in terms of self-other representations. Consciousness and Cognition, 20(4), 1744–1750.CrossRefPubMedGoogle Scholar
  5. Bellander, M., Backman, L., Liu, T., Schjeide, B. M., Bertram, L., Schmiedek, F., et al. (2015). Lower baseline performance but greater plasticity of working memory for carriers of the val allele of the COMT Val158Met polymorphism. Neuropsychology, 29(2), 247–254.CrossRefPubMedGoogle Scholar
  6. Bernstein, E. M., & Putnam, F. W. (1986). Development, reliability, and validity of a dissociation scale. The Journal of Nervous and Mental Disease, 174(12), 727–735.CrossRefPubMedGoogle Scholar
  7. Bilder, R. M., Volavka, J., Lachman, H. M., & Grace, A. A. (2004). The catechol-O-methyltransferase polymorphism: relations to the tonic-phasic dopamine hypothesis and neuropsychiatric phenotypes. Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology, 29(11), 1943–1961.CrossRefGoogle Scholar
  8. Blanke, O. (2012). Multisensory brain mechanisms of bodily self-consciousness. Nature Reviews Neuroscience, 13(8), 556–571.PubMedGoogle Scholar
  9. Bob, P., & Mashour, G. A. (2011). Schizophrenia, dissociation, and consciousness. Consciousness and Cognition, 20(4), 1042–1049.CrossRefPubMedGoogle Scholar
  10. Botvinick, M., & Cohen, J. (1998). Rubber hands ‘feel’ touch that eyes see. Nature, 391(6669), 756.CrossRefPubMedGoogle Scholar
  11. Botvinick, M. M. (2008). Hierarchical models of behavior and prefrontal function. Trends in Cognitive Sciences, 12(5), 201–208.CrossRefPubMedPubMedCentralGoogle Scholar
  12. Breier, A., Su, T. P., Saunders, R., Carson, R. E., Kolachana, B. S., de Bartolomeis, A., et al. (1997). Schizophrenia is associated with elevated amphetamine-induced synaptic dopamine concentrations: evidence from a novel positron emission tomography method. Proceedings of the National Academy of Sciences of the USA, 94(6), 2569–2574.CrossRefPubMedPubMedCentralGoogle Scholar
  13. Chen, J., Lipska, B. K., Halim, N., Ma, Q. D., Matsumoto, M., Melhem, S., Kolachana, B. S., et al. (2004). Functional analysis of genetic variation in catechol-O-methyltransferase (COMT): Effects on mRNA, protein, and enzyme activity in postmortem human brain. The American Journal of Human Genetics, 75(5), 807–821. CrossRefPubMedGoogle Scholar
  14. Colzato, L., S., van den Wildenberg, W. P., & Hommel, B. (2014). Cognitive control and the COMT Val158Met polymorphism: Genetic modulation of videogame training and transfer to task-switching efficiency. Psychological Research Psychologische Forschung, 78(5), 670–678.PubMedGoogle Scholar
  15. Colzato, L. S., Waszak, F., Nieuwenhuis, S., Posthuma, D., & Hommel, B. (2010). The flexible mind is associated with the Catechol-O-methyltransferase (COMT) Val158Met polymorphism: Evidence for a role of dopamine in the control of task switching. Neuropsychologia, 48(9), 2764–2768.CrossRefPubMedGoogle Scholar
  16. Cools, R., & D’Esposito, M. (2011). Inverted-U-shaped dopamine actions on human working memory and cognitive control. Biological Psychiatry, 69(12), e113–e125.CrossRefPubMedPubMedCentralGoogle Scholar
  17. Costantini, M., & Haggard, P. (2007). The rubber hand illusion: Sensitivity and reference frame for body ownership. Consciousness and Cognition, 16(2), 229–240.CrossRefPubMedGoogle Scholar
  18. Durgin, F. H., Evans, L., Dunphy, N., Klostermann, S., & Simmons, K. (2007). Rubber hands feel the touch of light. Psychological Science, 18(2), 152–157.CrossRefPubMedGoogle Scholar
  19. Ehrsson, H. H., Holmes, N. P., & Passingham, R. E. (2005). Touching a rubber hand: feeling of body ownership is associated with activity in multisensory brain areas. The Journal of Neuroscience, 25(45), 10564–10573.CrossRefPubMedPubMedCentralGoogle Scholar
  20. Ehrsson, H. H., Spence, C., & Passingham, R. E. (2004). That’s my hand! Activity in premotor cortex reflects feeling of ownership of a limb. Science, 305(5685), 875–877.CrossRefPubMedGoogle Scholar
  21. Fan, J. B., Zhang, C. S., Gu, N. F., Li, X. W., Sun, W. W., Wang, H. Y., et al. (2005). Catechol-O-methyltransferase gene Val/Met functional polymorphism and risk of schizophrenia: A large-scale association study plus meta-analysis. Biological Psychiatry, 57(2), 139–144.CrossRefPubMedGoogle Scholar
  22. Goes, F. S., McGrath, J., Avramopoulos, D., Wolyniec, P., Pirooznia, M., Ruczinski, I., et al. (2015). Genome-wide association study of schizophrenia in Ashkenazi Jews. American journal of medical genetics. Part B, Neuropsychiatric genetics, 168(8), 649–659.CrossRefGoogle Scholar
  23. Goghari, V. M., & Sponheim, S. R. (2008). Differential association of the COMT Val158Met polymorphism with clinical phenotypes in schizophrenia and bipolar disorder. Schizophrenia Research, 103(1–3), 186–191.CrossRefPubMedGoogle Scholar
  24. Haans, A., Ijsselsteijn, W. A., & de Kort, Y. A. (2008). The effect of similarities in skin texture and hand shape on perceived ownership of a fake limb. Body Image, 5(4), 389–394.CrossRefPubMedGoogle Scholar
  25. Honma, M., Koyama, S., & Osada, Y. (2009). Double tactile sensations evoked by a single visual stimulus on a rubber hand. Neuroscience Research, 65(3), 307–311.CrossRefPubMedGoogle Scholar
  26. Honma, M., Plass, J., Brang, D., Florczak, S. M., Grabowecky, M., & Paller, K. A. (2016). Sleeping on the rubber-hand illusion: memory reactivation during sleep facilitates multisensory recalibration. Neuroscience of Consciousness, 2016(1), niw020.CrossRefPubMedPubMedCentralGoogle Scholar
  27. Honma, M., Yoshiike, T., Ikeda, H., Kim, Y., & Kuriyama, K. (2014). Sleep dissolves illusion: Sleep withstands learning of visuo-tactile-proprioceptive integration induced by repeated days of rubber hand illusion training. PLoS One, 9(1), e85734.CrossRefPubMedPubMedCentralGoogle Scholar
  28. Jeon, H. A. (2014). Hierarchical processing in the prefrontal cortex in a variety of cognitive domains. Frontiers in Systems Neuroscience, 8, 223.CrossRefPubMedPubMedCentralGoogle Scholar
  29. Kihlstrom, J. F. (2005). Dissociative disorders. Annual Review of Clinical Psychology, 1, 227–253.CrossRefPubMedGoogle Scholar
  30. Koechlin, E., & Summerfield, C. (2007). An information theoretical approach to prefrontal executive function. Trends in Cognitive Sciences, 11(6), 229–235.CrossRefPubMedGoogle Scholar
  31. Krause-Utz, A., Veer, I. M., Rombouts, S. A., Bohus, M., Schmahl, C., & Elzinga, B. M. (2014). Amygdala and anterior cingulate resting-state functional connectivity in borderline personality disorder patients with a history of interpersonal trauma. Psychological Medicine, 44(13), 2889–2901.CrossRefPubMedGoogle Scholar
  32. Lachman, H. M., Papolos, D. F., Saito, T., Yu, Y. M., Szumlanski, C. L., & Weinshilboum, R. M. (1996). Human catechol-O-methyltransferase pharmacogenetics: Description of a functional polymorphism and its potential application to neuropsychiatric disorders. Pharmacogenetics, 6(3), 243–250.CrossRefPubMedGoogle Scholar
  33. Laruelle, M., Abi-Dargham, A., van Dyck, C. H., Gil, R., D’Souza, C. D., Erdos, J., et al. (1996). Single photon emission computerized tomography imaging of amphetamine-induced dopamine release in drug-free schizophrenic subjects. Proceedings of the National Academy of Sciences of the USA, 93(17), 9235–9240.CrossRefPubMedPubMedCentralGoogle Scholar
  34. Lenggenhager, B., Tadi, T., Metzinger, T., & Blanke, O. (2007). Video ergo sum: Manipulating bodily self-consciousness. Science, 317(5841), 1096–1099.CrossRefPubMedGoogle Scholar
  35. Limanowski, J., & Blankenburg, F. (2016). That’s not quite me: Limb ownership encoding in the brain. Social Cognitive and Affective Neuroscience, 11(7), 1130–1140.CrossRefPubMedGoogle Scholar
  36. Lloyd, D. M. (2007). Spatial limits on referred touch to an alien limb may reflect boundaries of visuo-tactile peripersonal space surrounding the hand. Brain and Cognition, 64(1), 104–109.CrossRefPubMedGoogle Scholar
  37. Longo, M. R., Cardozo, S., & Haggard, P. (2008). Visual enhancement of touch and the bodily self. Consciousness and Cognition, 17(4), 1181–1191.CrossRefPubMedGoogle Scholar
  38. Lopez, C., Halje, P., & Blanke, O. (2008). Body ownership and embodiment: vestibular and multisensory mechanisms. Clinical Neurophysiology, 38(3), 149–161.CrossRefPubMedGoogle Scholar
  39. Lotta, T., Vidgren, J., Tilgmann, C., Ulmanen, I., Melen, K., Julkunen, I., et al. (1995). Kinetics of human soluble and membrane-bound catechol O-methyltransferase: a revised mechanism and description of the thermolabile variant of the enzyme. Biochemistry, 34(13), 4202–4210.CrossRefPubMedGoogle Scholar
  40. Maeda, T., Kato, M., Muramatsu, T., Iwashita, S., Mimura, M., & Kashima, H. (2012). Aberrant sense of agency in patients with schizophrenia: forward and backward over-attribution of temporal causality during intentional action. Psychiatry Research, 198(1), 1–6.CrossRefPubMedGoogle Scholar
  41. Maravita, A., & Iriki, A. (2004). Tools for the body (schema). Trends in Cognitive Sciences, 8(2), 79–86.CrossRefPubMedGoogle Scholar
  42. Middleton, F. A., & Strick, P. L. (2000). Basal ganglia and cerebellar loops: Motor and cognitive circuits. Brain Research Brain Research Reviews, 31(2–3), 236–250.CrossRefPubMedGoogle Scholar
  43. Mier, D., Kirsch, P., & Meyer-Lindenberg, A. (2010). Neural substrates of pleiotropic action of genetic variation in COMT: A meta-analysis. Molecular Psychiatry, 15(9), 918–927.CrossRefPubMedGoogle Scholar
  44. Nolan, K. A., Bilder, R. M., Lachman, H. M., & Volavka, J. (2004). Catechol O-methyltransferase Val158Met polymorphism in schizophrenia: Differential effects of Val and Met alleles on cognitive stability and flexibility. American Journal of Psychiatry, 161(2), 359–361.CrossRefPubMedGoogle Scholar
  45. Peled, A., Ritsner, M., Hirschmann, S., Geva, A. B., & Modai, I. (2000). Touch feel illusion in schizophrenic patients. Biological Psychiatry, 48(11), 1105–1108.CrossRefPubMedGoogle Scholar
  46. Pope, C. A., & Kwapil, T. R. (2000). Dissociative experience in hypothetically psychosis-prone college students. The Journal of Nervous and Mental Disease, 188(8), 530–536.CrossRefPubMedGoogle Scholar
  47. Preston, C. (2013). The role of distance from the body and distance from the real hand in ownership and disownership during the rubber hand illusion. Acta Psychologia (Amst), 142(2), 177–183.CrossRefGoogle Scholar
  48. Ramakonar, H., Franz, E. A., & Lind, C. R. (2011). The rubber hand illusion and its application to clinical neuroscience. Journal of Clinical Neuroscience, 18(12), 1596–1601.CrossRefPubMedGoogle Scholar
  49. Shifman, S., Bronstein, M., Sternfeld, M., Pisante-Shalom, A., Lev-Lehman, E., Weizman, A., et al. (2002). A highly significant association between a COMT haplotype and schizophrenia. American Journal of Human Genetics, 71(6), 1296–1302.CrossRefPubMedPubMedCentralGoogle Scholar
  50. Shimada, S., Fukuda, K., & Hiraki, K. (2009). Rubber hand illusion under delayed visual feedback. PLoS One, 4(7), e6185.CrossRefPubMedPubMedCentralGoogle Scholar
  51. Simeon, D., Guralnik, O., Gross, S., Stein, D., J., Schmeidler, J., & Hollander, E. (1998). The detection and measurement of depersonalization disorder. The Journal of Nervous and Mental Disease, 186(9), 536–542.CrossRefPubMedGoogle Scholar
  52. Spiegel, D., Lewis-Fernandez, R., Lanius, R., Vermetten, E., Simeon, D., & Friedman, M. (2013). Dissociative disorders in DSM-5. Annual Review of Clinical Psychology, 9, 299–326.CrossRefPubMedGoogle Scholar
  53. Spitzer, C., Haug, H. J., & Freyberger, H. J. (1997). Dissociative symptoms in schizophrenic patients with positive and negative symptoms. Psychopathology, 30(2), 67–75.CrossRefPubMedGoogle Scholar
  54. Thakkar, K. N., Nichols, H. S., McIntosh, L. G., & Park, S. (2011). Disturbances in body ownership in schizophrenia: evidence from the rubber hand illusion and case study of a spontaneous out-of-body experience. PLoS One, 6(10), e27089.CrossRefPubMedPubMedCentralGoogle Scholar
  55. Tsakiris, M., Haggard, P., Franck, N., Mainy, N., & Sirigu, A. (2005). A specific role for efferent information in self-recognition. Cognition, 96(3), 215–231.CrossRefPubMedGoogle Scholar
  56. Tsuchimine, S., Yasui-Furukori, N., Kaneda, A., & Kaneko, S. (2013). Differential effects of the catechol-O-methyltransferase Val158Met genotype on the cognitive function of schizophrenia patients and healthy Japanese individuals. PLoS One, 8(11), e76763.CrossRefPubMedPubMedCentralGoogle Scholar
  57. Tunbridge, E. M., Harrison, P. J., & Weinberger, D. R. (2006). Catechol-o-methyltransferase, cognition, and psychosis: Val158Met and beyond. Biological Psychiatry, 60(2), 141–151.CrossRefPubMedGoogle Scholar
  58. Van den Stock, J., de Jong, S. J., Hodiamont, P. P., & de Gelder, B. (2011). Perceiving emotions from bodily expressions and multisensory integration of emotion cues in schizophrenia. Social Neuroscience, 6(5–6), 537–547.CrossRefPubMedGoogle Scholar
  59. Vijayakumari, A. A., John, J. P., Halahalli, H. N., Paul, P., Thirunavukkarasu, P., Purushottam, M., et al. (2015). Effect of polymorphisms of three genes mediating monoamine signalling on brain morphometry in schizophrenia and healthy subjects. Clinical Psychopharmacology and Neuroscience, 13(1), 68–82.CrossRefPubMedPubMedCentralGoogle Scholar
  60. Werner, J. D., Trapp, K., Wustenberg, T., & Voss, M. (2014). Self-attribution bias during continuous action-effect monitoring in patients with schizophrenia. Schizophrenia Research, 152(1), 33–40.CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  1. 1.Department of Adult Mental HealthCenter of Neurology and Psychiatry, National Institute of Mental Health, NationalTokyoJapan
  2. 2.Department of NeurologyShowa University School of MedicineTokyoJapan
  3. 3.Department of PsychiatryShiga University of Medical ScienceOtsuJapan
  4. 4.Research Center for Overwork-Related Disorders, National Institute of Occupational Safety and HealthKawasakiJapan

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