Biochemical and molecular genetic factors in habitual violence and antisocial alcoholism

Control and preventive interventions
  • Matti Virkkunen


Serotonin has been found to play a central role in impulsive and habitual violent tendencies and personality disorders, and there is much evidence supporting the inverse relationship between impulsivity/aggression and central serotonergic activity. Biological factors, such as low brain serotonin turnover together with glucose metabolism and low brain noradrenaline turnover have been predictive of further violence among prisoners who evidence Antisocial Personality Disorder (ASP)1,2. However, according to recent reviews, the role of noradrenaline in impulsive aggression is still unclear3. Some studies demonstrate that increa sing noradrenaline correlates to impulsive aggression, whereas other studies demonstrate an opposite relationship. The role of dopamine and gamma-aminobutyric acid in human studies of these aggressive behaviors is still unclear and requires further investigation.


Personality Disorder Maternal Smoking Borderline Personality Disorder Acute Tryptophan Depletion Violent Offender 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Virkkunen, M., De Jong, J., Bartko, J., Goodwin, F., and Linnoila, M., 1989, Relationship of psychobiological variables to recidivism in violent offenders and impulsive fire setters. Arch. Gen. Psychiat. 46: 600–603.PubMedCrossRefGoogle Scholar
  2. 2.
    Virkkunen, M., Eggert, M., Rawlings, R., and Linnoila, M., 1996, A prospective follow-up study of alcoholic violent offenders and fire setters. Arch Gen Psychiat. 53: 523–529.PubMedCrossRefGoogle Scholar
  3. 3.
    Oquendo, M.A., and Mann, J.J., 2000, The biology of impulsivity and suicidality. J Psychiatr. Clin North Am. 23:11–25.Google Scholar
  4. 4.
    Tiihonen, J., and Hakola, P., 1994, Psychiatric disorders and homicide recidivism. Am. J. Psychiat. 15:436–438.Google Scholar
  5. 5.
    Lappalainen, J., Long, J.C., Eggert, M., Ozaki, N., Robin, 2W., Brown, G.L., Naukkarinen, H., Virkkunen, M., Linnoila, M., and Goldman, D., 1998, Linkage of antisocial alcoholism to the serotonin 5-HTI B receptor gene in 2 populations. Arch Gen Psychiat. 55:989–994.Google Scholar
  6. 6.
    Saudou, F., Amara, D.A., Dierich, A., LeMeur, M., Ramboz, S., Segu, L., Buhot, M.C., and Hen, R., 1994, Enhanced aggressive behavior in mice lacking 5-HT1B receptor. Science 265: 1875–1878.PubMedCrossRefGoogle Scholar
  7. 7.
    Crabbe, J.C., Phillipps, T.J., Feller, D.J., Hen, R., Wenger, C.D., Lessov, C.N., and Schafer, G.L., 1996, Elevated alcohol consumption in null mutant mice lacking 5-LITI B serotonin receptors. Nature Genetics 14: 98–101.PubMedCrossRefGoogle Scholar
  8. 8.
    Fish, E.W., Faccidomo, S., and Miczek, K.A., 1999, Aggression heightened by alcohol or social instigation in mice: reduction by the 5HT(1B) receptor agonist CP-94,253. Psychopharmacol. (Berl). 146: 391–399.Google Scholar
  9. 9.
    Coccaro, E.F., Kavoussi, R.J., and Hanger, R.L., 1995, Physiological responses to dfenfluramine and ipsapirone challenge correlate with indices of aggression in males with personality disorders. Int. Clin. Psychopharmacol 10: 177–179.PubMedCrossRefGoogle Scholar
  10. 10.
    Cleare, A.J., and Bond, A.J., 2000, Experimental evidence that the aggressive effect of tryptophan depletion is mediated via the 5-HTIA receptor. Psychopharmacol. (Berl). 147: 439–441.Google Scholar
  11. 11.
    Nielsen, D.A., Virkkunen, M., Lappalainen, J., Eggert, M., Brown, G.L., Long, J.C., Goldman, D., and Linnoila, M., 1998, A tryptophan hydroxylase gene marker for suicidality and alcoholism. Arch. Gen. Psychiat. 55:593–602.Google Scholar
  12. 12.
    Rotondo, A., Schuebel, K., Bergen, A., Aragon, R., Virkkunen, M., Linnoila, M., Goldman, D., and Nielsen, D., 1999, Identification of four variants in the tryptophan hydroxylase promoter and association to behavior. Mot Psychiat. 4: 360–368.CrossRefGoogle Scholar
  13. 13.
    Manuck, S.B., Flory, J.D., Ferrell, R.E., Dent, K.M., Mann, J.J., and Muldoon, M..F., 1999, Aggression and anger-related traits associated with a polymorphism of the tryptophan hydroxylase gene. Biol. Psychiat. 45: 603–614.PubMedCrossRefGoogle Scholar
  14. 14.
    Radel, M., Vallejo, R.L., Long, J.C., and Goldman, D., 1999, Sib-pair linkage analysis of GABRG2 to alcohol dependence. Alcohol Clin Exp. Res. 23: 59A.Google Scholar
  15. 15.
    Buckley, P.F., 1999, The role of typical and atypical antipsychotic medications in the management of agitation and aggression. J Gin Psychiat. 60 (Suppl 10): 52–60.Google Scholar
  16. 16.
    Coccaro, E., and Kavoussi, R.J., 1997, Fluoxetine and impulsive aggressive behavior in personality-disordered subjects. Arch Gen. Psychiat. 54: 1081–1088.PubMedCrossRefGoogle Scholar
  17. 17.
    Oliver, B., Mos, J., Hartog, J., and Rasmussen, D., 1990, Serenics. Drugs, News and Perspectives 3: 261–271.Google Scholar
  18. 18.
    de Koning, P., Mak, M., de Vries, M.H., Allsopp L.F., Stevens, RB., Verbroggen, R., van den Borre, R., van Peteghem, P., Kohen, D., and Arumainayagam, M., 1994, Eltoprazine in aggressively mentally handicapped patients: a double-blind, placebo-and baseline-controlled multi-center study. Inter. Clin.Psychipharmacol. 9: 187–194.CrossRefGoogle Scholar
  19. 19.
    Sheard, M.H., Marini,l.L., Bridges, Cl.,. and Wagner, E., 1976, The effect of lithium on impulsive aggressive behavior in man. Am. J. Psychiat. 133: 1409–1413.Google Scholar
  20. 20.
    Fava, M., 1997, Psychopharmacologic treatment of pathologic aggression. Psychiat. Clin. North Ant 20: 427–451.CrossRefGoogle Scholar
  21. 21.
    Keck, P.E. Jr., Strakowski, S.M., and McElrory, S.L., 2000, The efficacy of atypical antipsychotics in the treatment of depressive symptoms, hostility, and suicidality in patients with schizophrenia J Clin Psychiat. 61 Suppl 3: 4–9.Google Scholar
  22. 22.
    Volavka, J., and Chrome, L., 1999, Atypical antipsychotics in the treatment of the persistently aggressive psychotic patient: methodological concerns. Schizophr. Res. 35 Suppl: S23 - S33.Google Scholar
  23. 23.
    Spivak, B., Roitman, S., Vered, Y., Mester, R., Graff, E., Talmon, Y., Guy, N., Gonen, N., and Weizman, A., 1998, Diminished suicidal and aggressive behavior, high plasma norepinephrine levels, and serum triglyceride levels in chronic neuroleptic-resistant schizophrenic patients maintained on clozapine. Clin. Neuropharmacol. 21: 245–250.PubMedGoogle Scholar
  24. 24.
    LeMarquand, D.G., Benkelfat, C., Phil, R.O., Palmour, R.M., and Young, S.N., 1999. Behavioral disinhibition induced by tryptophan depletion in nonalcoholic young men with multigenerational family histories of paternal alcoholism. Am. J. Psychiat. 156: 1771 1779.Google Scholar
  25. 25.
    Sainio, E-L., Pulkki, K., and Young, S.N., 1996, L-tryptophan: biochemical, nutritional and pharmacological aspects. Amino acids 10: 21–47.CrossRefGoogle Scholar
  26. 26.
    Hibbeln, J.R., Umhau, J.C., Linnoila, M., George, D.T., Ragan, P.W., Shoaf, S.E., Vaughan, M.R., Rawlings, R., and Salem, N. Jr., 1998, A replication study of violent and nonviolent subjects: cerebrospinal fluid metabolites of serotonin and dopamine are predicted by plasma essential fatty acids. Biol.Psychiat. 44: 243–249.PubMedCrossRefGoogle Scholar
  27. 27.
    Virkkunen, M.E., Horrobin, D.F., Jenkins, D.K., and Manku, M.S., 1987, Plasma phospholipid essential fatty acids and prostaglandins in alcoholic, habitually violent, and impulsive offenders Biol Psychiat. 22: 1087–1096.PubMedCrossRefGoogle Scholar
  28. 28.
    Vessby, B., 2000, Dietary fat and insulin action in humans. Brit. J. Nutr. 83 Suppl 1: S91 - S96.Google Scholar
  29. 29.
    Burgess, J.R., Stevens. L., Zhang, W., and Peck, L., 2000, Long-chain polyunsaturated fatty acids in children with attention-deficit hyperactivity disorder. Am J. Clin. Nutr. 71 (1 Suppl): 327S - 330S.Google Scholar
  30. 30.
    Hamazaki, T., Sawazaki, S., Itomura, M., Asaoka, E., Nogao, Y., Nishimura, N., Yazawa, K., Kuwamori, T., and Kobayashi M., 1996, The effect of docosahexaenoic acid on aggression in young adults. A placebo-controlled double-blind study. J. Clin. Invest. 97: 1129–1134.PubMedCrossRefGoogle Scholar
  31. 31.
    Hamazaki, T., Sawazaki, S., Nagar), Y., Kuwamori, T., Yazawa, K., Mizushima, Y., and Kobayashi, M., 1998, Docosahexaenoic acid does not affect aggression on normal volunteers under nonstressful conditions. A randomized, placebo-controlled, double-blind study. Lipids 33: 663–667.PubMedCrossRefGoogle Scholar
  32. 32.
    Wakslag, L.S., Lahey, B.B., Loeber, R., Green, S.M., Gordon, R.A., and Leventhal, B.L., 1997, Maternal smoking during pregnancy and the risk for conduct disorder in boys. Arch Gen. Psychiat. 54. 670–676Google Scholar
  33. 32.
    Fergusson, D.M., Woodward, L.J., and Horwood, L.J., 1998, Maternal smoking during pregnancy and psychiatric adjustment in late adolescence. Arch Gen. Psychiat. 55: 72 1727.Google Scholar
  34. 33.
    Brennan, P.A., Grekin, E.R., and Mednick, S.A., 1999, Maternal smoking during pregnancy and adult male criminal outcomes. Arch Gen. Psychiat. 56: 215–219.PubMedCrossRefGoogle Scholar
  35. 34.
    Rasanen, P., Hakko, H., Isohanni, M., Hodgins, S., Jarvelin, M-R., and Tiihonen, J., 1999, Maternal smoking during pregnancy and risk of criminal behavior among adult male offspring in the Northern Finland 1966 Birth Cohort. Am J. Psychiat. 156: 857–862.PubMedGoogle Scholar
  36. 35.
    Fergusson, D.M., 1999, Prenatal smoking and antisocial behavior. Arch. Gen. Psychiat. 56: 223–224.PubMedCrossRefGoogle Scholar
  37. 36.
    Paris, J., 1996, Antisocial personality disorder: a biopsychosocial model. Can. J. Psychiat. 41: 75–80.Google Scholar
  38. Paanila, J., Eronen, M., Hakola, P., and Tiihonen, J., 2000, Aging and homicide rates. J. Foren. Sci. 45: 390–391.Google Scholar

Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Matti Virkkunen
    • 1
  1. 1.Department of PsychiatryHelsinki University Central HospitalHelsinkiFinland

Personalised recommendations