Hostname: page-component-cd9895bd7-q99xh Total loading time: 0 Render date: 2024-12-29T03:51:29.510Z Has data issue: false hasContentIssue false
  • English
  • Français

Serotonin and impulsive aggression

Published online by Cambridge University Press:  22 May 2015

Emil F. Coccaro ,
Jennifer R. Fanning ,
K. Luan Phan  and
Royce Lee
Emil F. Coccaro*
Affiliation:
Clinical Neuroscience & Psychopharmacology Research Unit, Department of Psychiatry (MC#3077), Pritzker School of Medicine, University of Chicago, Chicago, Illinois, USA
Jennifer R. Fanning
Affiliation:
Clinical Neuroscience & Psychopharmacology Research Unit, Department of Psychiatry (MC#3077), Pritzker School of Medicine, University of Chicago, Chicago, Illinois, USA
K. Luan Phan
Affiliation:
Department of Psychiatry, University of Illinois College of Medicine, Chicago, Illinois, USA Mental Health Service Line, Jesse Brown Veterans Administration Medical Center, Chicago, Illinois, USA Departments of Psychology, and Anatomy and Cell Biology, University of Illinois at Chicago, Chicago, Illinois, USA
Royce Lee
Affiliation:
Clinical Neuroscience & Psychopharmacology Research Unit, Department of Psychiatry (MC#3077), Pritzker School of Medicine, University of Chicago, Chicago, Illinois, USA
*
*Address for correspondence: Emil Coccaro, University of Chicago, Department of Psychiatry, 5841 S. Maryland Avenue, MC 3077, Chicago, IL 60637, USA. (Email: [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Aggression is a behavior with evolutionary origins, but is often both destructive and maladaptive in today’s society. Research over the past several decades has confirmed the involvement of neurotransmitter function in aggressive behavior. This research has centered around the “serotonin hypothesis.” As this literature continues to grow, guided by pre-clinical research and aided by the application of increasingly sophisticated neuroimaging methodology, a more complex picture has emerged. As current pharmacological and therapeutic interventions are effective but imperfect, it is hoped that new insights into the neurobiology of aggression will reveal novel avenues for treatment of this destructive and costly behavior.

Keywords

Aggressionneuroimagingneurotransmittersreceptorsserotonin
Type
Review Articles
Information
CNS Spectrums , Volume 20 , Special Issue 3: Violence in the Psychiatric Setting , June 2015 , pp. 295 - 302
Copyright
© Cambridge University Press 2015 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1. Dodge, KA. The structure and function of reactive and proactive aggression. In: Peppler D, Rubin K eds. The Development and Treatment of Childhood Aggression. Hillsdale, NJ: Erlbaum; 1991: 201–218.Google Scholar
2. Coccaro, EF. Intermittent explosive disorder as a disorder of impulsive aggression for DSM-5. Am J Psychiatry. 2012; 169(6): 577–588.Google Scholar
3. Berman, ME, Fallon, AE, Coccaro, EF. The relationship between personality psychopathology and aggressive behavior in research volunteers. J Abnorm Psychol. 1998; 107(4): 651–658.Google Scholar
4. Kessler, RC, Coccaro, EF, Fava, M, Jaeger, S, Jin, R, Walters, E. The prevalence and correlates of DSM-IV intermittent explosive disorder in the National Comorbidity Survey Replication. Arch Gen Psychiatry. 2006; 63(6): 669–678.CrossRefGoogle ScholarPubMed
5. Yanowitch, R, Coccaro, EF. The neurochemistry of human aggression. Adv Genet. 2011; 75: 151–169.Google Scholar
6. Coccaro, EF, Kavoussi, RJ, Hauger, RL, Cooper, TB, Ferris, CF. Cerebrospinal fluid vasopressin levels: correlates with aggression and serotonin function in personality-disordered subjects. Arch Gen Psychiatry. 1998; 55(8): 708–714.Google Scholar
7. Coccaro, EF, Lee, R, Liu, T, Mathé, AA. CSF NPY correlates with aggression in human subjects. Biol Psychiatry. 2012; 72(12): 997–1003.Google Scholar
8. Coccaro, EF, Lee, R, Owens, MJ, Kinkead, B, Nemeroff, CB. Cerebrospinal fluid substance P-like immunoreactivity correlates with aggression in personality disordered subjects. Biol Psychiatry. 2012; 72(3): 238–243.CrossRefGoogle ScholarPubMed
9. Coccaro, EF, Lee, R, Vezina, P. Cerebrospinal fluid glutamate concentration correlates with impulsive aggression in human subjects. J Psychiatr Res. 2013; 47(9): 1247–1253.Google Scholar
10. Coccaro, EF, Lee, R, Coussons-Read, M. Elevated plasma inflammatory markers in individuals with intermittent explosive disorder and correlation with aggression in humans. JAMA Psychiatry. 2014; 71(2): 158–165.CrossRefGoogle ScholarPubMed
11. Asberg, M, Schalling, D, Traskman-Bendz, L, Wagner, A. Psychobiology of suicide, impulsivity, and related phenomena. In Davis K ed Psychopharmacology: The Third Generation of Progress. New York: Raven Press; 1987: 665–668.Google Scholar
12. Bourne, HR, Bunney, WE, Colburn, RW, et al. Noradrenaline, 5-hydroxytryptamine, and 5-hydroxyindoleacetic acid hindbrains of suicidal patients. Lancet. 1968; 2(7572): 805–808.CrossRefGoogle ScholarPubMed
13. Pare, CMB, Yeung, DPH, Price, K, Stacey, RS. 5-Hydroxytryptamine, noradrenaline, and dopamine in brainstem, hypothalamus, and caudate nucleus of controls and of patients committing suicide by coal-gas poisoning. Lanset. 1969; 2(7612): 133–135.Google Scholar
14. Shaw, DM, Eccleston, EG, Camps, FE. 5-Hydroxytryptamine in the hind-brain of depressive suicides. Br J Psychiatry. 1967; 113(505): 140–1411.CrossRefGoogle ScholarPubMed
15. Stanley, M, Traskman-Bendz, L, Dorovini-Zis, K. Correlations between aminergic metabolites simultaneously obtained from human CSF and brain. Life Sci. 1985; 37(14): 1279–1286.Google Scholar
16. Asberg, M, Träskman, L, Thorén, P. 5-HIAA in the cerebrospinal fluid: a biochemical suicide predictor? Arch Gen Psychiatry. 1976; 33(10): 1193–1197.CrossRefGoogle ScholarPubMed
17. Brown, GL, Goodwin, FK, Ballenger, JC, Goyer, PF, Major, LF. Aggression in humans correlates with cerebrospinal fluid amine metabolites. Psychiatry Res. 1979; 1(2): 131–139.Google Scholar
18. Brown, GL, Ebert, MH, Goyer, PF, et al. Aggression, suicide, and serotonin: relationships to CSF amine metabolites. Am J Psychiatry. 1982; 139(6): 741–746.Google Scholar
19. Lidberg, L, Tuck, JR, Asberg, M, Scalia-Tomba, GP, Bertilsson, L. Homicide, suicide, and CSF 5-HIAA. Acta Psychiatr Scand. 1985; 71(3): 230–236.Google Scholar
20. Lester, D. The concentration of neurotransmitter metabolites in cerebrospinal fluid of suicidal individuals: a meta-analysis. Pharmacopsychiatry. 1995; 28(2): 45–50.CrossRefGoogle ScholarPubMed
21. 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(10): 1430–1435.Google Scholar
22. Coccaro, EF, Kavoussi, RJ, Trestman, RL, Gabriel, SM, Cooper, TB, Siever, LJ. Serotonin function in human subjects: intercorrelations among central 5-HT indices and aggressiveness. Psychiatry Res. 1997; 73(1–2): 1–14.Google Scholar
23. Hibbeln, JR, Umhau, JC, George, DT, Shoaf, SE, Linnoila, M, Salem, N Jr. Plasma total cholesterol concentrations do not predict cerebrospinal fluid neurotransmitter metabolites: implications for the biophysical role of highly unsaturated fatty acids. Am J Clin Nutr. 2000; 71(1 Suppl): 331S–338S.Google Scholar
24. Simeon, D, Stanley, B, Frances, A, Mann, JJ, Winchel, R, Stanley, M. Self-mutilation in personality disorders: psychological and biological correlates. Am J Psychiatry. 1992; 149(2): 221–226.Google ScholarPubMed
25. Coccaro, EF, Lee, R. Cerebrospinal fluid 5-hydroxyindolacetic acid and homovanillic acid: reciprocal relationships with impulsive aggression in human subjects. J Neural Transm. 2010; 117(2): 241–248.CrossRefGoogle ScholarPubMed
26. Coccaro, EF, Siever, LJ, Klar, HM, et al. Serotonergic studies in patients with affective and personality disorders: correlates with suicidal and impulsive aggressive behavior. Arch Gen Psychiatry. 1989; 46(7): 587–599.Google Scholar
27. Coccaro, EF, Lee, R, Kavoussi, RJ. Aggression, suicidality, and intermittent explosive disorder: serotonergic correlates in personality disorder and healthy control subjects. Neuropsychopharmacology. 2010; 35(2): 435–444.Google Scholar
28. Suarez, EC, Krishnan, KR. The relation of free plasma tryptophan to anger, hostility, and aggression in a nonpatient sample of adult men and women. Ann Behav Med. 2006; 31(3): 254–260.CrossRefGoogle Scholar
29. Goveas, JS, Csernansky, JG, Coccaro, EF. Platelet serotonin content correlates inversely with life history of aggression in personality-disordered subjects. Psychiatry Res. 2004; 126(1): 23–32.CrossRefGoogle ScholarPubMed
30. Coccaro, E, Kavoussi, R, Sheline, Y, Lish, J, Csernansky, J. Impulsive aggression in personality disorder correlates with tritiated paroxetine binding in the platelet. Arch Gen Psychiatry. 1996; 53(6): 531–536.Google Scholar
31. Coccaro, EF, Kavoussi, RJ, Sheline, YI, Berman, ME, Csernansky, JG. Impulsive aggression in personality disorder correlates with platelet 5-HT2A receptor binding. Neuropsychopharmacology. 1997; 16(3): 211–216.CrossRefGoogle ScholarPubMed
32. Coccaro, EF, Lee, R, Kavoussi, RJ. Inverse relationship between numbers of 5-HT transporter binding sites and life history of aggression and intermittent explosive disorder. J Psychiatr Res. 2009; 44(3): 137–142.CrossRefGoogle ScholarPubMed
33. Marseille, R, Lee, R, Coccaro, EF. Inter-relationship between different platelet measures of 5-HT and their relationship to aggression in human subjects. Prog Neuropsychopharmacol Biol Psychiatry. 2012; 36(2): 277–281.CrossRefGoogle ScholarPubMed
34. New, AS, Trestman, RL, Mitropoulou, V, et al. Serotonergic function and self-injurious behavior in personality disorder patients. Psychiatry Res. 1997; 69(1): 17–26.Google Scholar
35. Paris, J, Zweig-Frank, H, Kin, NM, Schwartz, G, Steiger, H, Nair, NP. Neurobiological correlates of diagnosis and underlying traits in patients with borderline personality disorder compared with normal controls. Psychiatry Res. 2004; 121(3): 239–252.Google Scholar
36. O'Keane, V, Moloney, E, O'Neill, H, O'Connor, A, Smith, C, Dinan, TG. Blunted prolactin responses to d-fenfluramine in sociopathy: evidence for subsensitivity of central serotonergic function. Br J Psychiatry. 1992; 160(5): 643–646.Google Scholar
37. Moeller, FG, Steinberg, JL, Petty, F, et al. Serotonin and impulsive/aggressive behavior in cocaine dependent subjects. Prog Neuropsychopharmacol Biol Psychiatry. 1994; 18(6): 1027–1035.Google Scholar
38. Moss, HB, Yao, JK, Panzak, GL. Serotonergic responsivity and behavioral dimensions in antisocial personality disorder with substance abuse. Biol Psychiatry. 1990; 28(4): 325–338.CrossRefGoogle ScholarPubMed
39. Coccaro, EF, Berman, ME, Kavoussi, RJ, Hauger, RL. Relationship of prolactin response to d-fenfluramine to behavioral and questionnaire assessments of aggression in personality-disordered men. Biol Psychiatry. 1996; 40(3): 157–164.CrossRefGoogle ScholarPubMed
40. Moeller, FG, Allen, T, Cherek, DR, Dougherty, DM, Lane, S, Swann, AC. Ipsapirone neuroendocrine challenge: relationship to aggression as measured in the human laboratory. Psychiatry Res. 1998; 81(1): 31–38.CrossRefGoogle ScholarPubMed
41. Pihl, RO, Young, SN, Harden, P, Plotnick, S, Chamberlain, B, Ervin, FR. Acute effect of altered tryptophan levels and alcohol on aggression in normal human males. Psychopharmacology (Berl). 1995; 119(4): 353–360.Google Scholar
42. Cleare, AJ, Bond, AJ. The effect of tryptophan depletion and enhancement on subjective and behavioural aggression in normal male subjects. Psychopharmacology (Berl). 1995; 118(1): 72–81.CrossRefGoogle ScholarPubMed
43. Dougherty, DM, Bjork, JM, Marsh, D, Moeller, FG. Influence of trait hostility on tryptophan depletion-induced laboratory aggression. Psychiatry Res. 1999; 88(3): 227–232.CrossRefGoogle ScholarPubMed
44. Linnoila, M, Virkkunen, M, Scheinin, M, Nuutila, A, Rimon, R, Goodwin, FK. Low cerebrospinal fluid 5-hydroxyindoleacetic acid concentration differentiates impulsive from nonimpulsive violent behavior. Life Sci. 1983; 33(26): 2609–2614.Google Scholar
45. Spoont, MR. Modulatory role of serotonin in neural information processing: implications for human psychopathology. Psychol Bull. 1992; 112(2): 330–350.Google Scholar
46. Linnoila, VM, Virkkunen, M. Aggression, suicidality, and serotonin. J Clin Psychiatry. 1992; 53(Suppl): 46–51.Google ScholarPubMed
47. Coccaro, EF, Kavoussi, RJ, Lesser, JC. Self- and other-directed human aggression: the role of the central serotonergic system. Int Clin Psychopharmacol. 1992; 6(Suppl 6): 70–83.Google Scholar
48. Berman, ME, McCloskey, MS, Fanning, JR, Schumacher, JA, Coccaro, EF. Serotonin augmentation reduces response to attack in aggressive individuals. Psychol Sci. 2009; 20(6): 714–720.Google Scholar
49. Marks, DJ, Miller, SR, Schulz, KP, Newcorn, JH, Halperin, JM. The interaction of psychosocial adversity and biological risk in childhood aggression. Psychiatry Res. 2007; 151(3): 221–230.Google Scholar
50. Duke, AA, Bègue, L, Bell, R, Eisenlohr-Moul, T. Revisiting the serotonin-aggression relation in humans: a meta-analysis. Psychol Bull. 2013; 139(5): 1148–1172.CrossRefGoogle ScholarPubMed
51. Cleare, AJ, Bond, AJ. Ipsapirone challenge in aggressive men shows an inverse correlation between 5-HT1A receptor function and aggression. Psychopharmacology (Berl). 2000; 148(4): 344–349.CrossRefGoogle ScholarPubMed
52. Almeida, M, Lee, R, Coccaro, EF. Cortisol responses to ipsapirone challenge correlate with aggression, while basal cortisol levels correlate with impulsivity, in personality disorder and healthy volunteer subjects. J Psychiatr Res. 2010; 44(14): 874–880.Google Scholar
53. Bortolato, M, Pivac, N, Muck Seler, D, Nikolac Perkovic, M, Pessia, M, Di Giovanni, G. The role of the serotonergic system at the interface of aggression and suicide. Neuroscience. 2013; 236: 160–185.CrossRefGoogle ScholarPubMed
54. Olivier, B, van Oorschot, R. 5-HT1B receptors and aggression: a review. Eur J Pharmacol. 2005; 526(1–3): 207–217.Google Scholar
55. Meyer, JH, Wilson, AA, Rusjan, P, et al. Serotonin2A receptor binding potential in people with aggressive and violent behaviour. J Psychiatry Neurosci. 2008; 33(6): 499–508.Google Scholar
56. Soloff, PH, Price, JC, Mason, NS, Becker, C, Meltzer, CC. Gender, personality, and serotonin-2A receptor binding in healthy subjects. Psychiatry Research: Neuroimaging. 2010; 181(1): 77–84.Google Scholar
57. Rosell, DR, Thompson, JL, Slifstein, M, et al. Increased serotonin 2A receptor availability in the orbitofrontal cortex of physically aggressive personality disordered patients. Biol Psychiatry. 2010; 67(12): 1154–1162.Google Scholar
58. Siever, LJ, Buchsbaum, MS, New, AS, et al. d,l-fenfluramine response in impulsive personality disorder assessed with [18F]fluorodeoxyglucose positron emission tomography. Neuropsychopharmacology. 1999; 20(5): 413–423.Google Scholar
59. New, AS, Hazlett, EA, Buchsbaum, MS, et al. Blunted prefrontal cortical 18fluorodeoxyglucose positron emission tomography response to meta-chlorophenylpiperazine in impulsive aggression. Arch Gen Psychiatry. 2002; 59(7): 621–629.Google Scholar
60. New, AS, Buchsbaum, MS, Hazlett, EA, et al. Fluoxetine increases relative metabolic rate in prefrontal cortex in impulsive aggression. Psychopharmacology (Berl). 2004; 176(3–4): 451–458.Google Scholar
61. Leyton, M, Okazawa, H, Diksic, M, et al. Brain regional alpha-[11C]methyl-L-tryptophan trapping in impulsive subjects with borderline personality disorder. Am J Psychiatry. 2001; 158(5): 775–782.Google Scholar
62. Frankle, WG, Lombardo, I, New, AS, et al. Brain serotonin transporter distribution in subjects with impulsive aggressivity: a positron emission study with [11C]McN 5652. Am J Psychiatry. 2005; 162(5): 915–923.Google Scholar
63. Koch, W, Schaaff, N, Pöpperl, G, et al. [I-123] ADAM and SPECT in patients with borderline personality disorder and healthy control subjects. J Psychiatry Neurosci. 2007; 32(4): 234–240.Google Scholar
64. Coccaro, EF, Lee, R, Kavoussi, RJ. A double-blind, randomized, placebo-controlled trial of fluoxetine in patients with intermittent explosive disorder. J Clin Psychiatry. 2009; 70(5): 653–662.Google Scholar
65. George, DT, Phillips, MJ, Lifshitz, M, et al. Fluoxetine treatment of alcoholic perpetrators of domestic violence: a 12-week, double-blind, randomized, placebo-controlled intervention study. J Clin Psychiatry. 2011; 72(1): 60–65.Google Scholar
66. Silva, H, Iturra, P, Solari, A, et al. Fluoxetine response in impulsive-aggressive behavior and serotonin transporter polymorphism in personality disorder. Psychiatr Genet. 2010; 20(1): 25–30.Google Scholar
67. Heiligenstein, JH, Coccaro, EJ, Potvin, JH, Beasley, CM, Dornseif, BE, Mascia, DN. Fluoxetine not associated with increased violence or aggression in controlled clinical trials. Ann Clin Psychiatry. 1992; 4(4): 285–295.CrossRefGoogle Scholar
68. Salzman, C, Wolfson, AN, Schatzberg, A, et al. Effect of fluoxetine on anger in symptomatic volunteers with borderline personality disorder. J Clin Psychopharmacol. 1995; 15(1): 23–29.Google Scholar
69. Coccaro, EF, Kavoussi, RJ, Hauger, RL. Serotonin function and antiaggressive response to fluoxetine: a pilot study. Biol Psychiatry. 1997; 42(7): 546–552.Google Scholar
70. Coccaro, EF, Sripada, CS, Yanowitch, RN, Phan, KL. Corticolimbic function in impulsive aggressive behavior. Biol Psychiatry. 2011; 69(12): 1153–1159.CrossRefGoogle ScholarPubMed