Skip to main content

Relationship between dopamine system genes and extraversion and novelty seeking

Neuroscience and Behavioral Physiology volume 37, pages 601–606 (2007)Cite this article

Abstract

Dopamine transmission is known to play an important role in the reinforcement system of the brain. Studies have identified dopamine system genes whose polymorphic variants have been linked with the intensity of psychological traits reflecting the tendency to form behaviors characterized by impulsivity and the need for additional stimulation. The aim of the present work was to seek associations between polymorphisms in the catechol-O-methyltransferase (COMT) and D4 dopamine receptor (DRD4) genes and personality traits in the Russian population. Studies of 130 subjects showed that carriers of the Met/Met genotype of the COMT gene had a greater intensity of the novelty-seeking trait than carriers of the Val/Val and Val/Met genotypes, though this association was seen only in women. In addition, the presence of the C allele of the DRD4 gene in carriers of the Met/Met genotype showed high levels of extraversion and hypomania. These results are consistent with current theoretical concepts of the regulation of dopamine transmission in the brain.

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

References

  1. V. E. Golimbet, I. K. Gritsenko, M. V. Alfimova, and R. P. Ebstein, “Polymorphic markers of the promoter region of the D4 dopamine receptor gene and temperament in mentally healthy humans from the Russian population,” Genetika, 41, No. 7, 966–972 (2005).

    PubMed  CAS  Google Scholar 

  2. R. M. Bilder, J. Volavka, H. M. Lachman, and A. A. Grace, “The catechol-O-methyltransferase polymorphism: relations to the tonic-phasic dopamine hypothesis and neuropsychiatric phenotypes,” Neuropsychopharmacology, 29, No. 11, 1943–1961 (2004).

    Article  PubMed  CAS  Google Scholar 

  3. E. B. Bookman, R. E. Taylor, L. Adams-Campbell, and R. A. Kittles, “DRD4 promoter SNPs and gender effects on Extraversion in African Americans,” Mol. Psychiatry, 7, No. 7, 786–789 (2002).

    Article  PubMed  CAS  Google Scholar 

  4. J. Chen, B. K. Lipska, N. Halim, Q. D. Ma, M. Matsumoto, S. Melhem, B. S. Kolachana, T. M. Hyde, M. M. Herman, J. Apud, M. F. Egan, J. E. Kleinman, and D. R. Weinberger, “Functional analysis of genetic variation in catechol-O-methyltransferase (COMT): effects on mRNA, protein, and enzyme activity in postmortem human brain,” Amer. J. Hum. Genet., 75, No. 5, 807–821 (2004).

    Article  PubMed  CAS  Google Scholar 

  5. R. P. Ebstein, O. Novick, R. Umansky, B. Priel, Y. Osher, D. Blaine, E. R. Bennett, L. Nemanov, M. Katz, and R. H. Belmaker, “Dopamine D4 receptor (D4DR) exon III polymorphism associated with the human personality trait of Novelty Seeking,” Nat. Genet., 12, No. 1, 78–80 (1996).

    Article  PubMed  CAS  Google Scholar 

  6. J. Ekelund, J. Suhonen, M. R. Jarvelin, L. Peltonen, and D. Lichtermann, “No association of the −521 C/T polymorphism in the promoter of DRD4 with novelty seeking,” Mol. Psychiatry, 6, No. 6, 618–719 (2001).

    Article  PubMed  CAS  Google Scholar 

  7. J. A. Gogos, M. Morgan, V. Luine, M. Santha, S. Ogawa, D. Pfaff, and M. Karayiorgou, “Catechol-O-methyltransferase-deficient mice exhibit sexually dimorphic changes in catecholamine levels and behavior,” Proc. Natl. Acad. Sci. USA, 95, No. 17, 9991–9996 (1998).

    Article  PubMed  CAS  Google Scholar 

  8. H. Herken and M. E. Erdal, “Catechol-O-methyltransferase gene polymorphism in schizophrenia: evidence for association between symptomatology and prognosis,” Psychiatr. Genet., 11, No. 2, 105–109 (2001).

    Article  PubMed  CAS  Google Scholar 

  9. J. Kauhanen, T. Hallikainen, T. P. Tuomainen, M. Koulu, M. K. Karvonen, and J. T. Aalonen, “Association between the functional polymorphism of catechol-O-methyltransferase gene and alcohol consumption among social drinkers,” Alcoholism: Clin. Exptl. Res., 24, 135–139 (2000).

    Article  CAS  Google Scholar 

  10. H. J. Lachman, K. A. Nolan, P. Mohr, T. Saito, and J. Volavka, “Association between catechol O-methyltransferase genotype and violence in schizophrenia and schizoaffective disorder,” Amer. J. Psychiatry, 155, 835–837 (1998).

    CAS  Google Scholar 

  11. H. J. Lee, H. S. Lee, Y. K. Kim, S. H. Kim, L. Kim, M. S. Lee, S. H. Joe, I. K. Jung, K. Y. Suh, and S. Kim, “Allelic variants interaction of dopamine receptor D4 polymorphism correlate with personality traits in young Korean female population,” Amer. J. Med. Genet., 118B, No. 1, 76–80 (2003).

    Article  Google Scholar 

  12. A. K. Malhotra, L. J. Kestler, C. Mazzanati, J. A. Bates, T. Goldberg, and D. Goldman, “A functional polymorphism in the COMT gene and performance on a test of prefrontal cognition,” Amer. J. Psychiatry, 159, No. 4, 652–654 (2002).

    Article  Google Scholar 

  13. M. Matsumoto, K. Hidaka, S. Tada, Y. Tasaki, and T. Yamaguchi, “Low levels of mRNA for dopamine D4 receptor in human cerebral cortex and striatum,” J. Neurochem., 66, No. 3, 915–919 (1996).

    Article  PubMed  CAS  Google Scholar 

  14. M. Matsumoto, C. S. Weickert, S. Beltaifa, B. Kolachana, J. Chen, T. M. Hyde, M. M. Herman, D. R. Weinberger, and J. E. Kleinman, “Catechol O-methyltransferase (COMT) mRNA expression in the dorsolateral prefrontal cortex of patients with schizophrenia,” Neuropsychopharmacology, 28, No. 8, 1521–1530 (2003).

    Article  PubMed  CAS  Google Scholar 

  15. A. Meyer-Lindenberg, P. D. Kohn, B. Kolachana, S. Kippenham, A. McInerney-Leo, R. Nussbaum, D. R. Weinberger, and K. F. Berman, “Midbrain dopamine and prefrontal function in humans: interaction and modulation by COMT genotype,” Nat. Neurosci., 8, No. 5, 594–596 (2005).

    Article  PubMed  CAS  Google Scholar 

  16. K. A. Nolan, J. Volavka, P. Czobor, A. Cseh, H. Lachman, T. Saito, J. Tiihonen, A. Putkonen, T. Hallikainen, I. Kotilainen, P. Rasanen, M. Isohanni, M. R. Jarvelin, and M. K. Karvonen, “Suicidal behavior in patients with schizophrenia is related to COMT polymorphism,” Psychiatr. Genet., 10, 117–124 (2000).

    Article  PubMed  CAS  Google Scholar 

  17. Y. Okuyama, H. Ishiguro, M. Nankai, H. Shibuya, A. Watanabe, and T. Arinami, “Identification of a polymorphism in the promoter region of DRD4 associated with the human novelty seeking personality trait,” Mol. Psychiatry, 5, 64–69 (2000).

    Article  PubMed  CAS  Google Scholar 

  18. M. A. Palmatier, A. M. Kang, and K. K. Kidd, “Global variation in the frequencies of functionally different catechol-O-methyltransferase alleles,” Biol. Psychiatry, 46, No. 4, 557–567 (1999).

    Article  PubMed  CAS  Google Scholar 

  19. M. Reuter and J. Hennig, “Association of the functional catechol-O-methyltransferase VAL158MET polymorphism with the personality trait of extraversion,” Neuroreport, 16, No. 10, 1135–1138 (2005).

    Article  PubMed  CAS  Google Scholar 

  20. Z. Ronai, A. Szekely, Z. Nemoda, K. Lakatos, J. Gervai, M. Staub, and M. Sasvari-Szekely, “Association between Novelty Seeking and the −521 C/T polymorphism in the promoter region of the DRD4 gene,” Mol. Psychiatry, 6, No. 1, 35–38 (2001).

    Article  PubMed  CAS  Google Scholar 

  21. A. Rotondo, C. Mazzanti, L. Dell-Osso, P. Rucci, P. Sullivan, S. Bouanani, C. Gonnelli, D. Goldman, and G. B. Cassano, “Catechol-O-methyltransferase, serotonin transporter, and tryptophan hydroxylase gene polymorphisms in bipolar disorder patients with and without comorbid panic disorder,” Amer. J. Psychiatry, 159, 23–29 (2002).

    Article  Google Scholar 

  22. M. Rubinstein, T. J. Phillips, J. R. Bunzow, T. L. Falzone, G. Dziewczapolski, G. Zhang, Y. Fang, J. L. Larson, J. A. McDougall, J. A. Chester, C. Saez, T. A. Pugsley, O. Gershanik, M. J. Low, and D. K. Grundy, “Mice lacking dopamine D4 receptors are supersensitive to ethanol, cocaine, and methamphetamine,” Cell, 90, 991–1001 (1997).

    Article  PubMed  CAS  Google Scholar 

  23. D. Rujescu, I. Giegling, A. Gietl, A. M. Hartmann, and H. J. Moller, “A functional single nucleotide polymorphism (V158M) in the COMT gene is associated with aggressive personality traits,” Biol. Psychiatry, 54, 34–39 (2003).

    Article  PubMed  CAS  Google Scholar 

  24. I. S. Sanya and H. H. Van Tol, “Review of the role of dopamine D4 receptors in schizophrenia and antipsychotic action,” J. Psychiatr. Res., 31, No. 2, 219–232 (1997).

    Article  Google Scholar 

  25. J. A. Schinka, E. A. Letsch, and F. C. Crawford, “DRD4 and novelty seeking: results of meta-analyses,” Amer. J. Med. Genet., 114, No. 6, 643–648 (2002).

    Article  CAS  Google Scholar 

  26. S. Shifman, M. Bronstein, M. Sternfeld, A. Pisante-Shalom, E. Lev-Lehman, A. Weizman, I. Reznik, B. Spivak, N. Grisaru, L. Karp, R. Schiffer, M. Kotler, R. D. Strous, M. Swartz-Vanetik, H.Y. Knobler, E. Shinar, J. S. Beckmann, B. Yakir, N. Risch, N. B. Zak, and A. Darvasi, “A highly significant association between a COMT haplotype and schizophrenia,” Amer. J. Hum. Genet., 71, No. 6, 1296–1302 (2002).

    Article  PubMed  CAS  Google Scholar 

  27. R. D. Strous, N. Bark, S. S. Parsia, J. Volavka, and H. M. Lachman, “Analysis of a functional catechol-O-methyl-transferase gene polymorphism in schizophrenia: evidence for association with aggressive and antisocial behavior,” Psychiatry Res., 69, 71–77 (1997).

    Article  PubMed  CAS  Google Scholar 

  28. S. J. Tsai, C. J. Hong, Y. W. Yu, and T. J. Chen, “Association study of catechol-O-methyltransferase gene and dopamine D4 receptor gene polymorphisms and personality traits in healthy young Chinese females,” Neuropsychobiology, 50, No. 2, 153–156 (2004).

    Article  PubMed  CAS  Google Scholar 

  29. E. M. Tunbridge, D. M. Bannerman, T. Sharp, and P. J. Harrison, “Catechol-O-methyltransferase inhibition improves set-shifting performance and elevates stimulated dopamine release in the rat prefrontal cortex,” J. Neurosci., 24, No. 23, 5331–5335 (2004).

    Article  PubMed  CAS  Google Scholar 

  30. D. R. Weinberger, M. F. Egan, A. Bertolino, J. H. Callicott, V. S. Mattay, B. K. Lipska, K. F. Berman, and T. E. Goldberg, “Prefrontal neurons and the genetics of schizophrenia,” Biol. Psychiatry, 50, No. 11, 825–844 (2001).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Scientific Center for Mental Health, Russian Academy of Medical Sciences, Moscow

    V. E. Golimbet & M. V. Alfimova

  2. Department of Psychology, Scheinfeld Center of Human Genetics, Hebrew University, Israel

    I. K. Gritsenko & R. P. Ebstein

Authors
  1. V. E. Golimbet
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. V. Alfimova
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. I. K. Gritsenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. R. P. Ebstein
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

__________

Translated from Zhurnal Vysshei Nervnoi Deyatel’nosti imeni I. P. Pavlova, Vol. 56, No. 4, pp. 457–463, July–August, 2006.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Golimbet, V.E., Alfimova, M.V., Gritsenko, I.K. et al. Relationship between dopamine system genes and extraversion and novelty seeking. Neurosci Behav Physiol 37, 601–606 (2007). https://doi.org/10.1007/s11055-007-0058-8

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11055-007-0058-8

Key words

  • dopamine
  • reinforcement system
  • gene polymorphism
  • novelty-seeking
  • extraversion
  • dopamine receptor
  • catechol-O-methyltransferase