Current Psychiatry Reports

, Volume 2, Issue 2, pp 95–101 | Cite as

Serotonin and aggression in children

  • Effie M. Mitsis
  • Jeffrey M. Halperin
  • Jeffrey H. Newcorn
Article

Abstract

Research consistently indicates that in animals and adults, reduced central serotonergic (5-HT) function is associated with increased aggression. This relationship has been elucidated via cerebrospinal fluid monoamine metabolite levels, hormonal responses to pharmacologic challenge using serotonergic probes, platelet receptor binding studies, and, more recently, through molecular genetic approaches. In contrast, studies examining the relationship of 5-HT to aggression in children have been characterized by inconsistent findings. The literature examining the relationship between central 5-HT function and aggression is reviewed. Several hypotheses that might account for the discrepancies in the child literature are examined.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References and Recommended Reading

  1. 1.
    Cadoret RJ, Cain MS: Environmental and genetic factors in predicting adolescent antisocial behavior in adoptees. Psychiatric Journal of the University of Ottowa 1981, 6:220–225.Google Scholar
  2. 2.
    Kolvin I, Miller FJW, Fleeting M, Kolvin PA: Social and parenting factors affecting criminal-offense rates: findings from the Newcastle thousand family study (1947-1980). Br J Psychiatry 1988, 152:80–90.PubMedCrossRefGoogle Scholar
  3. 3.
    Loeber R, Wung P, Keenan K, et al.: Developmental pathways in disruptive child behavior. Dev Psychopathol 1993, 5:103–133.Google Scholar
  4. 4.
    Olweus D: Stability of aggressive reaction patterns in males: a review. Psychol Bull 1979, 86:852–857.PubMedCrossRefGoogle Scholar
  5. 5.
    Botchin MB, Kaplan JR, Manuck SB, Mann JJ: Low versus high prolactin responders to fenfluramine challenge: marker of behavioral differences in adult male cynomolgus macaques. Neuropsychopharmacology 1993, 9:93–99.PubMedGoogle Scholar
  6. 6.
    Higley JD, Mehlman PT, Taub DM, et al.: Cerebrospinal fluid monoamine and adrenal correlates of aggression in free-ranging rhesus monkeys. Arch Gen Psychiatry 1992, 49:436–441.PubMedGoogle Scholar
  7. 7.
    Raleigh MJ, McGuire MT: Animal analogues of ostracism: biological mechanisms and social consequences. Ethol Sociobiol 1986, 7:53–66.Google Scholar
  8. 8.
    Soubrie P: Reconciling the role of central serotonin neurons in human and animal behavior. Behav Brain Sci 1986, 9:319–364.CrossRefGoogle Scholar
  9. 9.
    Coccaro EF, Siever LJ, Klar HM, et al.: Serotonergic studies in patients with affective and personality disorders. Arch Gen Psychiatry 1989, 46:587–599.PubMedGoogle Scholar
  10. 10.
    Linnoila M, Virkkunen M, Dvhrinin M, et al.: Low cerbrospinalfluid 5-hydroxyindoleacetic acid concentration differentiates impulsive from nonimpulsive violent behavior. Life Sci 1983, 33:2609–2614.PubMedCrossRefGoogle Scholar
  11. 11.
    O’Keane V, Moloney E, O’Neil H, et al.: Blunted prolactin responses to d-fenfluramine in sociopathy: evidence for subsensitivity of central serotonergic function. Br J Psychiatry 1992, 160:643–646.PubMedGoogle Scholar
  12. 12.
    Virkkunen M, Goldman D, Nielsen DA, Linnoila M: Low brain serotonin turnover rate (low CSF 5-HIAA) and impulsive violence. J Psychiatry Neurosci 1995, 20:271–275.PubMedGoogle Scholar
  13. 13.
    Fishbein DH, Lozovsky D, Jaffe JH: Impulsivity, aggression, and neuroendocrine responses to serotonergic stimulation in substance abusers. Biol Psychiatry 1989, 25:1049–1066.PubMedCrossRefGoogle Scholar
  14. 14.
    Manuck SB, Flory JD, Ferrell RE, et al.: Aggression, impulsivity, and central nervous system serotonergic responsivity in a nonpatient sample. Neuropsychopharmacology 1998, 19:287–299.PubMedCrossRefGoogle Scholar
  15. 15.
    Manuck SB, Flory JD, Ferrell RE, et al.: Aggression and angerrelated traits associated with a polymorphism of the tryptophan hydroxylase gene. Biol Psychiatry 1999, 45:603–614.PubMedCrossRefGoogle Scholar
  16. 16.
    New AS, Gelernter J, Yovell Y, et al.: Tryptophan hydroxylase genotype is associated with impulsive-aggression measures: a preliminary study. Am J Med Genet (Neuropsychiatric Genet) 1998, 81:13–17.CrossRefGoogle Scholar
  17. 17.
    Brown GL, Ebert MH, Goyer PF, et al.: Aggression, suicide, and serotonin: relationships to CSF amine metabolites. Am J Psychiatry 1982, 139:741–746.PubMedGoogle Scholar
  18. 18.
    Lidberg L, Tuck JR, Asberg M, et al.: Homicide, suicide and CSF 5-HIAA. Acta Psychiatr Scand, 1985, 71:230–236.PubMedGoogle Scholar
  19. 19.
    Cleare AJ, Bond AJ: Does central serotonergic function correlate inversely with aggression? A study using d-fenfluramine in healthy subjects. Psychiatry Res 1997, 69:89–95.PubMedCrossRefGoogle Scholar
  20. 20.
    Mehlman PT, Higley JD, Faucher I, et al.: Low CSF 5-HIAA concentrations and severe aggression and impaired impulse control in nonhuman primates. Am J Psychiatry 1994, 151:1485–1491.PubMedGoogle Scholar
  21. 21.
    Mehlman PT, Higley JD, Faucher I, et al.: Correlation of CSF 5-HIAA concentration with sociality and the timing of emigration in free-ranging primates. Am J Psychiatry 1995, 152:907–913.PubMedGoogle Scholar
  22. 22.
    Higley JD, King ST, Hasert MF, et al.: Stability of interindividual differences in serotonin function and its relationship to severe aggression and competent social behavior in rhesus macaque females. Neuropsychopharmacology 1996, 14:67–76.PubMedCrossRefGoogle Scholar
  23. 23.
    Kruesi MJP, Rapoport JL, Hamburger S, et al.: Cerebrospinal fluid monoamine metabolites, aggression, and impulsivity in disruptive behavior disorders of children and adolescents. Arch Gen Psychiatry 1990, 47:419–426.PubMedGoogle Scholar
  24. 24.
    Kruesi MJP, Hibbs E, Zahn TP, et al.: A 2-year prospective follow-up study of children and adolescents with disruptive behavior disorders. Arch Gen Psychiatry 1992, 49:429–435.PubMedGoogle Scholar
  25. 25.
    Castellanos FX, Elia J, Kruesi MJP, et al.: Cerebrospinal fluid monoamine metabolites in boys with attention-deficit hyperactivity disorder. Psychiatry Res 1994, 52:305–316.PubMedCrossRefGoogle Scholar
  26. 26.
    Clarke RA, Murphy DL, Constantino JN: Serotonin and externalizing behavior in young children. Psychiatry Res 1999, 86:29–40. Found the relationship between central 5-HT and behavioral deviance in infants to be weak, if present at all.PubMedCrossRefGoogle Scholar
  27. 27.
    Constantino JN, Murphy DL: Monoamine metabolites in ‘leftover’ newborn human cerebrospinal fluid-a potential resource for biobehavioral research. Psychiatry Res 1996, 65:129–142.PubMedCrossRefGoogle Scholar
  28. 28.
    Halperin JM, Sharma V, Siever LJ, et al.: Serotonergic function in aggressive and nonaggressive boys with attention deficit hyperactivity disorder. Am J Psychiatry 1994, 151:243–248.PubMedGoogle Scholar
  29. 29.
    Halperin JM, Newcorn JH, Schwartz ST, et al.: Age-related changes in the association between serotonergic function and aggression in boys with ADHD. Biol Psychiatry 1997, 41:682–689.PubMedCrossRefGoogle Scholar
  30. 30.
    Pine DS, Coplan JD, Wasserman GA, et al.: Neuroendocrine response to fenfluramine challenge in boys. Associations with aggressive behavior and adverse rearing. Arch Gen Psych 1997, 54:839–846.Google Scholar
  31. 31.
    Stoff DM, Pasatiempo AP, Yeung JH, et al.: Neuroendocrine responses to challenge with dl-fenfluramine and aggression in disruptive behavior disorders of children and adolescents. Psychiatry Res 1992, 43:263–276.PubMedCrossRefGoogle Scholar
  32. 32.
    Grayson RH, Halperin JM, Sharma V, et al.: Changes in plasma prolactin and catecholamine metabolite levels following acute needle-stick in children. Psychiatry Res 1997, 69:27–32.PubMedCrossRefGoogle Scholar
  33. 33.
    Birmaher B, Stanley M, Greenhill L, et al.: Platelet imipramine binding in children and adolescents with impulsive behavior. J Am Acad Child Adolesc Psychiatry 1990, 29:914–918.PubMedCrossRefGoogle Scholar
  34. 34.
    Stoff DM, Pollock L, Vitiello B, et al.: Reduction of (3H)-Imipramine binding sites on platelets of conduct-disordered children. Neuropsychopharmacology 1987, 1:55–62.PubMedCrossRefGoogle Scholar
  35. 35.
    Donovan A, Halperin JM, Newcorn JH, Sharma V: Thermal response to serotonergic challenge and aggression in ADHD children. J Child Adolesc Psychopharmacology 1999, 9:85–91.CrossRefGoogle Scholar
  36. 36.
    Pine DS, Wasserman G, Coplan J, et al.: Serotonergic and cardiac correlates of aggression in children. Proc NY Acad Sci 1996, 794:391–393.CrossRefGoogle Scholar
  37. 37.
    Schulz KP, Newcorn JH, McKay KE, et al.: Central serotonergic function and aggression in boys: effect of ADHD. Scientific Proceedings of the Annual Meeting of the American Academy of Child and Adolescent Psychiatry. 1998, 14:91.Google Scholar
  38. 38.
    Lidlow MS, Goldman-Rakic PS, Rakic P: Synchronized overproduction of neurotransmitter receptors in diverse regions of the primate cerebral cortex. Proc Natl Acad Sci 1991, 88:10218–10221.CrossRefGoogle Scholar
  39. 39.
    Higley JD, Suomi SJ, Linnoila M: CSF monoamine metabolite concentrations vary according to age, rearing, and sex, and are influenced by the stress or os social separation in rhesus monkeys. Psychopharmacology 1991, 103:551–556.PubMedCrossRefGoogle Scholar
  40. 40.
    Langlais PJ, Walsh FX, Bird ED, Levy HL: Cerebrospinal fluid neurotransmitter metabolites in neurologically normal infants and children. Pediatrics 1985, 75:580–586.PubMedGoogle Scholar
  41. 41.
    Silverstein FS, Donn S, Buchanan K, Johnston MV: Concentrations of homovanillic acid and 5-hydroxyindoleacetic acid in cerebrospinal fluid from human infants in the perinatal period. J Neurochem 1985, 43:1769–1772.CrossRefGoogle Scholar
  42. 42.
    Pick LH, Halperin JM, Schwartz ST, Newcorn JH: A longitudinal study of neurobiological mechanisms in boys with attention-deficit hyperactivity disorder: preliminary findings. Biol Psychiatry 1999, 45:373–373. The only study to examine stability of central 5-HT function in children with DBDs.CrossRefGoogle Scholar
  43. 43.
    Cases O, Seif I, Grimsby J, et al.: Aggressive behavior and altered amounts of brain serotonin and norepinephrine in mice lacking MAOA. Science 1995, 268:1763–1766.PubMedCrossRefGoogle Scholar
  44. 44.
    Loeber R, Stouthamer-Loeber M: Development of juvenile aggression and violence. Am Psychologist 1998, 242–259.Google Scholar
  45. 45.
    Lyons MJ, True WT, Eisen SA, et al.: Differential heritability of adult and juvenile antisocial traits. Arch Gen Psychiatry 1995, 52:906–915.PubMedGoogle Scholar
  46. 46.
    Biederman J, Munir K, Knee D: Conduct and oppositional disorder in clinically referred children with attention deficit disorder: a controlled family study. J Am Acad Child Adolesc Psychiat 1987, 26:724–727.CrossRefGoogle Scholar
  47. 47.
    Frick PJ, Lahey BB, Loeber R, et al.: Familial risk factors to oppositional defiant disorder and conduct disorder: parental psychopathology and maternal parenting. J Consult Clin Psychol 1992, 60:49–55.PubMedCrossRefGoogle Scholar
  48. 48.
    Lahey BB, Piacentini JC, McBurnett K, et al.: Psychopathology in the parents of children with conduct disorder and hyperactivity. J Am Acad Child Adolesc Psychiatry 1988, 27:163–170.PubMedCrossRefGoogle Scholar
  49. 49.
    Coccaro EF, Silverman JM, Klar HM, et al.: Familial correlates of reduced central serotonergic system function in patients with personality disorders. Arch Gen Psychiatry 1994, 51:318–324.PubMedGoogle Scholar
  50. 50.
    Constantino JN, Morris JA, Murphy DL: CSF 5-HIAA and family history of antisocial personality disorder in newborns. Am J Psychiatry 1997, 154:1771–1773.PubMedGoogle Scholar
  51. 51.
    Constantino JN, Murphy DL, Morris JA: Family psychiatric history, cerebrospinal fluid monoamine metabolites, and temperament in infants. Biol Psychiatry 1999,45:626–632.PubMedCrossRefGoogle Scholar
  52. 52.
    Halperin JM, Newcorn JH, Kopstein I, et al.: Serotonin, aggression, and parental psychopathology in children with attention-deficit hyperactivity disorder. J Amer Acad Child Adol Psychiatry 1997, 36:1391–1398.CrossRefGoogle Scholar
  53. 53.
    Ernouf D, Compagnon P, Lothion P, et al.: Platelets in 3H 5HT uptake in descendants from alcoholic patients: a potential risk factor for alcohol dependence. Life Science 1993, 52:989–995.CrossRefGoogle Scholar
  54. 54.
    Cadoret RJ, Yates WR, Troughton E, et al.: Genetic-environmental interaction in the genesis of aggressivity and conduct disorders. Arch Gen Psychiatry 1995, 52:916–924.PubMedGoogle Scholar
  55. 55.
    Higley JD, Thompson WW, Champoux M, et al.: Paternal and maternal genetic and environmental contributions to cerebrospinal fluid monoamine metabolites in rhesus monkeys (macaca mulatta). Arch Gen Psychiatry 1993, 50:615–623.PubMedGoogle Scholar
  56. 56.
    Seroczynski AD, Bergeman CS, Coccaro EF: Etiology of the impulsivity/aggression relationship: genes or environment. Psychiatry Research 1999, 86:41–57. Examined the impact of genetic and environmental factors in the development of aggression in adults.PubMedCrossRefGoogle Scholar
  57. 57.
    Coccaro EF, Bergeman CS, McClearn GE: Heritability of irritable aggressiveness: a study of twins reared together and apart. Psychiatry Res 1993, 48:229–242.PubMedCrossRefGoogle Scholar
  58. 58.
    Ghodsian-Carpey J, Baker LA: Genetic and environmental influences on aggression in 4-to 7-year-old twins. Aggressive Behav 1987, 13:173–186.CrossRefGoogle Scholar
  59. 59.
    Kraemer GW, Ebert MH, Schmidt DE, McKinney WT: A longitudinal study of the effect of different social rearing conditions on cerebrospinal fluid norepinephrine and biogenic amine metabolites in rhesus monkeys. Neuropsychopharmacology 1989, 2:175–189.PubMedCrossRefGoogle Scholar
  60. 60.
    Kraemer GW, Clarke S: Social attachment, brain function, and aggression. Ann N Y Acad Sci 1996, 794:121–135.PubMedCrossRefGoogle Scholar
  61. 61.
    Nielsen DA, Goldman D, Virkkunen M, et al.: Suicidality and 5-hydroxyindoleacetic acid concentration associated with a tryptophan hydroxylase polymorphism. Arch Gen Psychiatry 1994, 51:34–38.PubMedGoogle Scholar
  62. 62.
    Coccaro EF, Kavoussi RJ, Cooper TB, Hauger RL: Central serotonin activity and aggression: inverse relationship with prolactin response to d-fenfluramine, but not CSF 5-HIAA concentration, in human subjects. Am J Psychiatry 1997, 154:1430–1435.PubMedGoogle Scholar
  63. 63.
    Glennon RA, Dukat M: Serotonin receptro subtypes. In Psychopharmacology: The Fourth Generation of Progress. Edited by Ploom FE, Kupfe DJ. New York: Raven Press; 1995:415–429.Google Scholar
  64. 64.
    Olivier B, Mos J: Serotonin receptor subtypes and aggressive behavior. Neuropsychopharmacology 1994, 10:944s.Google Scholar
  65. 65.
    de Boer SF, Lesourd M, Mocaer E, Koolhaas JM: Selective antiaggressive effects of alnespirone in resident-intruder test are mediated via 5-hydroxytryptamine1A receptors: a comparative pharmacological study with 8-hydroxy-2-dipropylaminotetralin, ipsapirone, buspirone, eltoprazine, and WAY-100635. J Pharmacol Exp Ther 1998, 288:1125–1133.Google Scholar
  66. 66.
    Virkkunen M, Eggert M, Rawlings R, Linnoila M: A prospective follow-up study of alcoholic violent offenders and fire setters. Arch Gen Psychiatry 1996, 53:523–529.PubMedGoogle Scholar
  67. 67.
    Lappalainen J, Dean M, Charbonneau L, et al.: Mapping of the serotonin 5-HT1D autoreceptor gene on chromosome 6 using a coding region polymorphism. Am J Med Genet 1995, 60:157–161.PubMedCrossRefGoogle Scholar
  68. 68.
    Miczek KA, Weerts EM, Vivian JA, Barros HM: Aggression, anxiety, and vocalizations in animals: GABAA and 5-HT anxiolytics. Psychopharmacology 1995, 121:38–56.PubMedCrossRefGoogle Scholar
  69. 69.
    Sanchez C, Arnt J, Hyttel J, Moltzen EK: The role of serotonergic mechanisms in inhibition of isolation-induced aggression in male mice. Psychopharmacology 1993, 110:53–59.PubMedCrossRefGoogle Scholar
  70. 70.
    Hen R, Saudou F, Amara A, et al.: Mice lacking 5-hydroxytryptamine 1B receptors display aggressive behavior. Soc Neurosci Abstr 1994, 20:1266.Google Scholar
  71. 71.
    Saudou F, Amara DA, Dierich A, et al.: Enhanced aggressive behavior in mice lacking 5-HT1B receptor. Science 1994, 265:1875–1878.PubMedCrossRefGoogle Scholar
  72. 72.
    Moffitt TE: Adolescence-limited and life-course-persistent antisocial behavior: a developmental taxonomy. Psychol Rev 1993, 100:674–701.PubMedCrossRefGoogle Scholar

Copyright information

© Current Science Inc 2000

Authors and Affiliations

  • Effie M. Mitsis
    • 1
  • Jeffrey M. Halperin
    • 1
    • 2
  • Jeffrey H. Newcorn
    • 2
  1. 1.Department of PsychologyQueens CollegeFlushingUSA
  2. 2.Department of PsychiatryMount Sinai School of MedicineNew YorkUSA

Personalised recommendations