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Population and Molecular Genetics of Anger and Aggression: Current State of the Art

  • Martin Reuter
Chapter

Abstract

Twin and adoption studies have demonstrated that about half of the variance in the aggression–hostility–anger (AHA) syndrome can be accounted for by genes. This strong heritability gives rise to the question which genes influence this facet of our personality that determines the proclivity for being aggressive or angry. Due to revolutionary progress in the field of molecular genetics over the last years first candidate genes for AHA have been identified. This chapter gives a short introduction in population and molecular genetics of anger and aggression. The most influential findings are reviewed. It becomes apparent that besides variations on genes coding for gonadal hormones, polymorphisms of serotonergic and dopaminergic neurotransmitter genes seem to be more relevant. Future perspectives in molecular genetic research are discussed that will help to unravel the genetic underpinnings of anger and aggression.

Keywords

Genetic Association Study Dizygotic Twin Androgen Receptor Gene COMT Gene TPH1 Gene 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Asberg, M., & Traskman, L. (1981). Studies of CSF 5-HIAA in depression and suicidal behaviour. Advances in Experimental Medicine and Biology, 133, 739–752.PubMedGoogle Scholar
  2. Beitchman, J. H., Baldassarra, L., Mik, H., De Luca, V., King, N., Bender, D., et al. (2006). Serotonin transporter polymorphisms and persistent, pervasive childhood aggression. American Journal of Psychiatry, 163, 1103–1105.PubMedCrossRefGoogle Scholar
  3. Bergman, A., Karlsson, P., Berggren, J., Martinsson, T., Bjorck, K., Nilsson, S., et al. (2007). Genome-wide linkage scan for breast cancer susceptibility loci in Swedish hereditary non-BRCA1/2 families: Suggestive linkage to 10q23.32-q25.3. Genes Chromosomes and Cancer, 46, 302–309.PubMedCrossRefGoogle Scholar
  4. Bioulac, B., Benezech, M., Renaud, B., Roche, D., & Noel, B. (1978). Biogenic amines in 47, XYY syndrome. Neuropsychobiology, 4, 366–370.PubMedCrossRefGoogle Scholar
  5. Bouchard, T. J., Jr. (1994). Genes, environment, and personality. Science, 264, 1700–1701.PubMedCrossRefGoogle Scholar
  6. Brown, G. L., Goodwin, F. K., Ballenger, J. C., Goyer, P. F., & Major, L. F. (1979). Aggression in humans correlates with cerebrospinal fluid amine metabolites. Psychiatry Research, 1, 131–139.PubMedCrossRefGoogle Scholar
  7. Bulayeva, K. B., Glatt, S. J., Bulayev, O. A., Pavlova, T. A., & Tsuang, M. T. (2007). Genome-wide linkage scan of schizophrenia: A cross-isolate study. Genomics, 89, 167–177.PubMedCrossRefGoogle Scholar
  8. Buss, A. H., & Durkee, A. (1957). An inventory for assessing different kinds of hostility. Journal of Consulting Psychology, 21, 343–349.PubMedCrossRefGoogle Scholar
  9. Coccaro, E. F., Bergeman, C. S., Kavoussi, R. J., & Seroczynski, A. D. (1997). Heritability of aggression and irritability: A twin study of the Buss–Durkee aggression scales in adult male subjects. Biological Psychiatry, 41, 273–284.PubMedCrossRefGoogle Scholar
  10. Coccaro, E. F., Bergeman, C. S., & McClearn, G. E. (1993). Heritability of irritable impulsiveness: A study of twins reared together and apart. Psychiatry Research, 48, 229–242.PubMedCrossRefGoogle Scholar
  11. Comings, D. E., Johnson, J. P., Gonzalez, N. S., Huss, M., Saucier, G., McGue, M., et al. (2000). Association between the adrenergic alpha 2A receptor gene (ADRA2A) and measures of irritability, hostility, impulsivity and memory in normal subjects. Psychiatric Genetics, 10, 39–42.PubMedCrossRefGoogle Scholar
  12. Contini, V., Marques, F. Z., Garcia, C. E., Hutz, M. H., & Bau, C. H. (2006). MAOA-uVNTR polymorphism in a Brazilian sample: Further support for the association with impulsive behaviors and alcohol dependence. American Journal of Medical Genetics B Neuropsychiatric Genetics, 141, 305–308.CrossRefGoogle Scholar
  13. Ducci, F., Newman, T. K., Funt, S., Brown, G. L., Virkkunen, M., & Goldman, D. (2006). A functional polymorphism in the MAOA gene promoter (MAOA-LPR) predicts central dopamine function and body mass index. Molecular Psychiatry, 11, 858–866.PubMedCrossRefGoogle Scholar
  14. Frankle, W. G., Lombardo, I., New, A. S., Goodman, M., Talbot, P. S., Huang, Y., et al. (2005). Brain serotonin transporter distribution in subjects with impulsive aggressivity: A positron emission study with [11C]McN 5652. American Journal of Psychiatry, 162, 915–923.PubMedCrossRefGoogle Scholar
  15. Gatewood, J. D., Wills, A., Shetty, S., Xu, J., Arnold, A. P., Burgoyne, P. S., et al. (2006). Sex chromosome complement and gonadal sex influence aggressive and parental behaviors in mice. Journal of Neuroscience, 26, 2335–2342.PubMedCrossRefGoogle Scholar
  16. Gerra, G., Garofano, L., Bosari, S., Pellegrini, C., Zaimovic, A., Moi, G., & et al. (2004). Analysis of monoamineoxidase A (MAO-A) promoter polymorphism in male heroin-dependent subjects:behavioural and personality correlates. Journal of Neural Transmission. 111, 611–621.Google Scholar
  17. Gerra, G., Garofano, L., Castaldini, L., Rovetto, F., Zaimovic, A., Moi, G., et al. (2005). Serotonin transporter promoter polymorphism genotype is associated with temperament, personality traits and illegal drugs use among adolescents. Journal of Neural Transmission, 112, 1397–1410.PubMedCrossRefGoogle Scholar
  18. Greenberg, B. D., Tolliver, T. J., Huang, S. J., Li, Q., Bengel, D., & Murphy, D. L. (1999). Genetic variation in the serotonin transporter promoter region affects serotonin uptake in human blood platelets. American Journal of Medical Genetics, 88, 83–87.PubMedCrossRefGoogle Scholar
  19. Haberstick, B. C., Smolen, A., & Hewitt, J. K. (2006). Family-based association test of the 5HTTLPR and aggressive behavior in a general population sample of children. Biological Psychiatry, 59, 836–843.PubMedCrossRefGoogle Scholar
  20. Han, D. H., Kee, B. S., Min, K. J., Lee, Y. S., Na, C., Park, D. B., et al. (2006). Effects of catechol-O-methyltransferase Val158Met polymorphism on the cognitive stability and aggression in the first-onset schizophrenic patients. NeuroReport, 17, 95–99.PubMedCrossRefGoogle Scholar
  21. Han, D. H., Park, D. B., Na, C., Kee, B. S., & Lee, Y. S. (2004). Association of aggressive behavior in Korean male schizophrenic patients with polymorphisms in the serotonin transporter promoter and catecholamine-O-methyltransferase genes. Psychiatry Research, 129, 29–37.PubMedCrossRefGoogle Scholar
  22. Hebebrand, J., Dempfle, A., Saar, K., Thiele, H., Herpertz-Dahlmann, B., Linder, M., et al. (2006). A genome-wide scan for attention-deficit/hyperactivity disorder in 155 German sib-pairs. Molecular Psychiatry, 11, 196–205.PubMedCrossRefGoogle Scholar
  23. Hennig, J., Reuter, M., Netter, P., Burk, C., & Landt, O. (2005). Two types of aggression are differentially related to serotonergic activity and the A779C TPH polymorphism. Behavioral Neuroscience, 119, 16–25.PubMedCrossRefGoogle Scholar
  24. Jones, G., Zammit, S., Norton, N., Hamshere, M. L., Jones, S. J., Milham, C., et al. (2001). Aggressive behaviour in patients with schizophrenia is associated with catechol-O-methyltransferase genotype. British Journal of Psychiatry, 179, 351–355.PubMedCrossRefGoogle Scholar
  25. Jönsson, E. G., Goldman, D., Spurlock, G., Gustavsson, J. P., Nielsen, D. A., Linnoila, M., Owen, M. J., & Sedvall, G. C. (1997). Tryptophan hydroxylase and catechol-O-methyltransferase gene polymorphisms: relationships to monoamine metabolite concentrations in CSF of healthy volunteers. European Archives of Psychiatry and Clinical Neuroscience, 247, 297–302.Google Scholar
  26. Jonsson, E. G., von Gertten, C., Gustavsson, J. P., Yuan, Q. P., Lindblad-Toh, K., Forslund, K., et al. (2001). Androgen receptor trinucleotide repeat polymorphism and personality traits. Psychiatric Genetics, 11, 19–23.PubMedCrossRefGoogle Scholar
  27. Lachman, H. M., Nolan, K. A., Mohr, P., Saito, T., & Volavka, J. (1998). Association between catechol O-methyltransferase genotype and violence in schizophrenia and schizoaffective disorder. American Journal of Psychiatry, 155, 835–837.PubMedGoogle Scholar
  28. 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, 243–250.PubMedCrossRefGoogle Scholar
  29. Lesch, K. P., Bengel, D., Heils, A., Sabol, S. Z., Greenberg, B. D., & Petri, S., (1996). Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science, 274, 1527–1531.Google Scholar
  30. Loehlin, J. C., Jonsson, E. G., Gustavsson, J. P., Schalling, M., & Stallings, M. C. (2003). The androgen receptor gene and psychological traits: Are results consistent in Sweden and Australia? Twin Research, 6, 201–208.PubMedCrossRefGoogle Scholar
  31. Mann, J. J., Malone, K. M., Nielsen, D. A., Goldman, D., Erdos, J., & Gelernter, J. (1997). Possible association of a polymorphism of the tryptophan hydroxylase gene with suicidal behavior in depressed patients. American Journal of Psychiatry, 154, 1451–1453.Google Scholar
  32. Manuck, S. B., Flory, J. D., Ferrell, R. E., Dent, K. M., Mann, J. J., & Muldoon, M. F. (1999). Aggression and anger-related traits associated with a polymorphism of the tryptophan hydroxylase gene. Biological Psychiatry, 45, 603–614.PubMedCrossRefGoogle Scholar
  33. Manuck, S. B., Flory, J. D., Ferrell, R. E., Mann, J. J., & Muldoon, M. F. (2000). A regulatory polymorphism of the monoamine oxidase-A gene may be associated with variability in aggression, impulsivity, and central nervous system serotonergic responsivity. Psychiatry Research, 95, 9–23.PubMedCrossRefGoogle Scholar
  34. McCrae, R. R., Costa, P. T., Jr., Pedroso de Lima, M., Simoes, A., Ostendorf, F., Angleitner, A., et al. (1999). Age differences in personality across the adult life span: Parallels in five cultures. Developmental Psychology, 35, 466–477.PubMedCrossRefGoogle Scholar
  35. New, A. S., Gelernter, J., Yovell, Y., Trestman, R. L., Nielsen, D. A., Silverman, J., et al. (1998). Tryptophan hydroxylase genotype is associated with impulsive-aggression measures: A preliminary study. American Journal of Medical Genetics, 81, 13–17.PubMedCrossRefGoogle Scholar
  36. Nielsen, D. A., Goldman, D., Virkkunen, M., Tokola, R., Rawlings, R., & Linnoila, M. (1994). Suicidality and 5-hydroxyindoleacetic acid concentration associated with a tryptophan hydroxylase polymorphism. Archives of General Psychiatry, 51, 34–38.PubMedGoogle Scholar
  37. Nielsen, D. A., Virkkunen, M., Lappalainen, J., Eggert, M., Brown, G. L., Long, J. C., et al. (1998). A tryptophan hydroxylase gene marker for suicidality and alcoholism. Archives of General Psychiatry, 55, 593–602.PubMedCrossRefGoogle Scholar
  38. Nolan, K. A., Volavka, J., Lachman, H. M., & Saito, T. (2000). An association between a polymorphism of the tryptophan hydroxylase gene and aggression in schizophrenia and schizoaffective disorder. Psychiatric Genetics, 10, 109–115.PubMedCrossRefGoogle Scholar
  39. Nomura, M., Andersson, S., Korach, K. S., Gustafsson, J. A., Pfaff, D. W., & Ogawa, S. (2006). Estrogen receptor-beta gene disruption potentiates estrogen-inducible aggression but not sexual behaviour in male mice. European Journal of Neuroscience, 23, 1860–1868.PubMedCrossRefGoogle Scholar
  40. Pillai, S. G., Chiano, M. N., White, N. J., Speer, M., Barnes, K. C., Carlsen, K., et al. (2006). A genome-wide search for linkage to asthma phenotypes in the genetics of asthma international network families: Evidence for a major susceptibility locus on chromosome 2p. European Journal of Human Genetics, 14, 307–316.PubMedCrossRefGoogle Scholar
  41. Reuter, M., & Hennig, J. (2005a). Pleiotropic effect of the TPH A779C polymorphism on nicotine dependence and personality. American Journal of Medical Genetics B Neuropsychiatric Genetics, 134, 20–24.CrossRefGoogle Scholar
  42. Reuter, M., & Hennig, J. (2005b). Association of the functional catechol-O-methyltransferase VAL158MET polymorphism with the personality trait of extraversion. NeuroReport, 16, 1135–1138.PubMedCrossRefGoogle Scholar
  43. Robins, D. M. (2005). Androgen receptor and molecular mechanisms of male-specific gene expression. Novartis Foundation Symposium, 268, 42–52.PubMedCrossRefGoogle Scholar
  44. Rujescu, D., Giegling, I., Bondy, B., Gietl, A., Zill, P., & Moller, H. J. (2002). Association of anger-related traits with SNPs in the TPH gene. Molecular Psychiatry, 7, 1023–1029.PubMedCrossRefGoogle Scholar
  45. Rujescu, D., Giegling, I., Gietl, A., Hartmann, A. M., & Moller, H. J. (2003). A functional single nucleotide polymorphism (V158M) in the COMT gene is associated with aggressive personality traits. Biological Psychiatry, 54, 34–39.PubMedCrossRefGoogle Scholar
  46. Rujescu, D., Giegling, I., Sato, T., Hartmann, A. M., & Moller, H. J. (2003). Genetic variations in tryptophan hydroxylase in suicidal behavior: Analysis and meta-analysis. Biological Psychiatry, 54, 465–473.PubMedCrossRefGoogle Scholar
  47. Sakai, J. T., Young, S. E., Stallings, M. C., Timberlake, D., Smolen, A., Stetler, G. L., et al. (2006). Case-control and within-family tests for an association between conduct disorder and 5HTTLPR. American Journal of Medical Genetics B Neuropsychiatric Genetics, 141, 825–832.CrossRefGoogle Scholar
  48. Sapolsky, R. M. (1991). Testicular function, social rank and personality among wild baboons. Psychoneuroendocrinology, 16, 281–293.PubMedCrossRefGoogle Scholar
  49. Setchell, J. M., & Dixson, A. F. (2001). Changes in the secondary sexual adornments of male mandrills (Mandrillus sphinx) are associated with gain and loss of alpha status. Hormones & Behavior, 39, 177–184.CrossRefGoogle Scholar
  50. Shih, J. C. (2004). Cloning, after cloning, knock-out mice, and physiological functions of MAO A and B. Neurotoxicology, 25, 21–30.PubMedCrossRefGoogle Scholar
  51. Smyth, D. J., Cooper, J. D., Bailey, R., Field, S., Burren, O., Smink, L. J., et al. (2006). A genome-wide association study of nonsynonymous SNPs identifies a type 1 diabetes locus in the interferon-induced helicase (IFIH1) region. Nature Genetics, 38, 617–619.PubMedCrossRefGoogle Scholar
  52. Staner, L., Uyanik, G., Correa, H., Tremeau, F., Monreal, J., Crocq, M. A., et al. (2002). A dimensional impulsive-aggressive phenotype is associated with the A218C polymorphism of the tryptophan hydroxylase gene: A pilot study in well-characterized impulsive inpatients. American Journal of Medical Genetics, 114, 553–557.PubMedCrossRefGoogle Scholar
  53. Strous, R. D., Bark, N., Parsia, S. S., Volavka, J., & Lachman, H. M. (1997). Analysis of a functional catechol-O-methyltransferase gene polymorphism in schizophrenia: Evidence for association with aggressive and antisocial behavior. Psychiatry Research, 69, 71–77.PubMedCrossRefGoogle Scholar
  54. Strous, R. D., Nolan, K. A., Lapidus, R., Diaz, L., Saito, T., & Lachman, H. M. (2003). Aggressive behavior in schizophrenia is associated with the low enzyme activity COMT polymorphism: A replication study. American Journal of Medical Genetics B Neuropsychiatric Genetics, 120, 29–34.Google Scholar
  55. Trainor, B. C., Greiwe, K. M., & Nelson, R. J. (2006). Individual differences in estrogen receptor alpha in select brain nuclei are associated with individual differences in aggression. Hormones and Behavior, 50, 338–345.PubMedCrossRefGoogle Scholar
  56. Tsai, S. J., Wang, Y. C., Chen J. Y., & Hong, C. J. (2003). Allelic variants of the tryptophan hydroxylase (A218C) and serotonin 1B receptor (A-161T) and personality traits. Neuropsychobiology, 48, 68–71.Google Scholar
  57. Volavka, J., Bilder, R., & Nolan, K. (2004). Catecholamines and aggression: The role of COMT and MAO polymorphisms. Annals of the New York Academy of Sciences, 1036, 393–398.PubMedCrossRefGoogle Scholar
  58. Westberg, L., Melke, J., Landen, M., Nilsson, S., Baghaei, F., Rosmond, R., et al. (2003). Association between a dinucleotide repeat polymorphism of the estrogen receptor alpha gene and personality traits in women. Molecular Psychiatry, 8, 118–122.PubMedCrossRefGoogle Scholar
  59. Widom, C. S., & Brzustowicz, L. M. (2006). MAOA and the “cycle of violence:” Childhood abuse and neglect, MAOA genotype, and risk for violent and antisocial behavior. Biological Psychiatry, 60, 684–689.PubMedCrossRefGoogle Scholar
  60. Zuckerman, M. (1984). Sensation seeking: A comparative approach to a human trait. Behavioral and Brain Sciences, 7, 413–471.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Department of PsychologyUniversity of BonnBonnGermany

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