Advertisement

Journal of Neural Transmission

, Volume 117, Issue 2, pp 241–248 | Cite as

Cerebrospinal fluid 5-hydroxyindolacetic acid and homovanillic acid: reciprocal relationships with impulsive aggression in human subjects

  • Emil F. Coccaro
  • Royce Lee
Biological Psychiatry - Original Article

Abstract

While the relationship between cerebrospinal fluid 5-HIAA (CSF 5-HIAA) and aggression is typically reported as inverse, studies of some groups of aggressive individuals demonstrate a positive (or no) relationship, between these two variables. It is possible that simultaneous examination of both CSF 5-HIAA and CSF homovanillic acid (HVA), which co-vary in human subjects may clarify differences in reported findings in different groups of aggressive individuals. CSF 5-HIAA and CSF HVA concentrations were simultaneously examined in 60 healthy human subjects (40 with personality disorder and 20 healthy controls) and were correlated with measures of aggression and impulsivity. CSF 5-HIAA concentrations correlated positively, and CSF HVA concentrations correlated inversely, with a composite measure of impulsive aggression in all subjects as well as in the personality disordered subjects. The CSF 5-HIAA findings are consistent with those demonstrating reduced post-synaptic 5-HT receptor responsiveness to 5-HT agent challenge and suggest differences in the pathophysiology between different groups of subjects with aggressive behavior, particularly with regard to severity of aggressive behavior.

Keywords

CSF 5-HIAA HVA Aggression Impulsivity Personality 

Notes

Acknowledgments

This work was supported in part by grants from the National Institute of Mental Health: RO-1 MH46848 and KO-2 MH00095 (Dr. Coccaro).

Conflict of interest statement

None.

References

  1. Agren H, Mefford IN, Rudorfer MV, Linnoila M, Potter WZ (1986) Interacting neurotransmitter systems. A non-experimental approach to the 5HIAA-HVA correlation in human CSF. J Psychiatr Res 20(3):175–193CrossRefPubMedGoogle Scholar
  2. American Psychiatric Association (1994) Diagnostic and statistical manual of mental disorders, 4th edn. American Psychiatric Association Press, Washington, DCGoogle Scholar
  3. Ashby P, Verrier M, Warsh JJ, Price KS (1976) Spinal reflexes and the concentrations of 5-HIAA, MHPG, and HVA in lumbar cerebrospinal fluid after spinal lesions in man. J Neurol Neurosurg Psychiatry 39(12):1191–1200CrossRefPubMedGoogle Scholar
  4. Barton DA, Esler MD, Dawood T, Lambert EA, Haikerwal D, Brenchley C et al (2008) Elevated brain serotonin turnover in patients with depression: effect of genotype and therapy. Arch Gen Psychiatry 65(1):38–46CrossRefPubMedGoogle Scholar
  5. Brown GL, Goodwin FK, Ballenger JC, Goyer PF, Major LF (1979) Aggression in humans correlates with cerebrospinal fluid amine metabolites. Psychiatry Res 1(2):131–139CrossRefPubMedGoogle Scholar
  6. Brown GL, Ebert MH, Goyer PF, Jimerson DC, Klein WJ, Bunney WE et al (1982) Aggression, suicide, and serotonin: relationships to CSF amine metabolites. Am J Psychiatry 139(6):741–746PubMedGoogle Scholar
  7. Bunce SC, Noblett KL, McCloskey MS, Coccaro EF (2005) High prevalence of personality disorders among healthy volunteers for research: implications for control group bias. J Psychiatr Res 39(4):421–430CrossRefPubMedGoogle Scholar
  8. Buss AH, Durkee A (1957) An inventory for assessing different kinds of hostility. J Consult Psychol 21(4):343–349CrossRefPubMedGoogle Scholar
  9. Castellanos FX, Elia J, Kruesi MJ, Gulotta CS, Mefford IN, Potter WZ et al (1994) Cerebrospinal fluid monoamine metabolites in boys with attention-deficit hyperactivity disorder. Psychiatry Res 52(3):305–316CrossRefPubMedGoogle Scholar
  10. Coccaro E, Siever L (2002) Pathophysiology and treatment of aggression. In: Psychopharmacology: the fifth generation of progress, pp 1709–1723Google Scholar
  11. Coccaro EF, Siever LJ (2005) Neurobiology of personality disorder. In: Oldham JM, Skodol AE, Bender D (eds) Textbook of personality disorders. American Psychiatric Press, Arlington, pp 155–169Google Scholar
  12. Coccaro EF, Kavoussi RJ, Sheline YI, Lish JD, Csernansky JG (1996) Impulsive aggression in personality disorder correlates with tritiated paroxetine binding in the platelet. Arch Gen Psychiatry 53(6):531–536PubMedGoogle Scholar
  13. Coccaro EF, Berman ME, Kavoussi RJ (1997a) Assessment of life history of aggression: development and psychometric characteristics. Psychiatry Res 73(3):147–157CrossRefPubMedGoogle Scholar
  14. Coccaro EF, Kavoussi RJ, Cooper TB, Hauger RL (1997b) 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 154(10):1430–1435PubMedGoogle Scholar
  15. Coccaro EF, Kavoussi RJ, Trestman RL, Gabriel SM, Cooper TB, Siever LJ (1997c) Serotonin function in human subjects: intercorrelations among central 5-HT indices and aggressiveness. Psychiatry Res 73(1–2):1–14CrossRefPubMedGoogle Scholar
  16. Coccaro EF, Schmidt CA, Samuels JF, Nestadt G (2004) Lifetime and 1-month prevalence rates of intermittent explosive disorder in a community sample. J Clin Psychiatry 65(6):820–824PubMedCrossRefGoogle Scholar
  17. Curzon G, Gumpert EJ, Sharpe DM (1971) Amine metabolites in the lumbar cerebrospinal fluid of humans with restricted flow of cerebrospinal fluid. Nat New Biol 231(23):189–191PubMedGoogle Scholar
  18. Emerson AJ, Kappenman DP, Ronan PJ, Renner KJ, Summers CH (2000) Stress induces rapid changes in serotonergic activity: restraint and exertion. Behav Brain Res 111(1–2):83–92CrossRefPubMedGoogle Scholar
  19. Engstrom G, Alling C, Blennow K, Regnell G, Traskman-Bendz L (1999) Reduced cerebrospinal HVA concentrations and HVA/5-HIAA ratios in suicide attempters. Monoamine metabolites in 120 suicide attempters and 47 controls. Eur Neuropsychopharmacol 9(5):399–405CrossRefPubMedGoogle Scholar
  20. Eysenck SB, Eysenck HJ (1977) The place of impulsiveness in a dimensional system of personality description. Br J Soc Clin Psychol 16(1):57–68PubMedGoogle Scholar
  21. Fri CG, Wiesel FA, Sedvall G (1974) Simultaneous quantification of homovanillic acid and 5-hydroxyindoleacetic acid in cerebrospinal fluid by mass fragmentography. Life Sci 14(12):2469–2480CrossRefPubMedGoogle Scholar
  22. Garelis E, Young SN, Lal S, Sourkes TL (1974) Monoamine metabolites in lumbar CSF: the question of their origin in relation to clinical studies. Brain Res 79(1):1–8CrossRefPubMedGoogle Scholar
  23. Geldof M, Freijer JI, Peletier LA, van Beijsterveldt L, Danhof M (2008) Mechanistic model for the acute effect of fluvoxamine on 5-HT and 5-HIAA concentrations in rat frontal cortex. Eur J Pharm Sci 33(3):217–229PubMedGoogle Scholar
  24. Gillman PK, Bartlett JR, Bridges PK, Hunt A, Patel AJ, Kantamaneni BD et al (1981) Indolic substances in plasma, cerebrospinal fluid, and frontal cortex of human subjects infused with saline or tryptophan. J Neurochem 37(2):410–417CrossRefPubMedGoogle Scholar
  25. Grahame-Smith DG (1971) Studies in vivo on the relationship between brain tryptophan, brain 5-HT synthesis and hyperactivity in rats treated with a monoamine oxidase inhibitor and l-tryptophan. J Neurochem 18(6):1053–1066CrossRefPubMedGoogle Scholar
  26. Higley JD, Mehlman PT, Taub DM, Higley SB, Suomi SJ, Vickers JH et al (1992) Cerebrospinal fluid monoamine and adrenal correlates of aggression in free-ranging rhesus monkeys. Arch Gen Psychiatry 49(6):436–441PubMedGoogle Scholar
  27. Kishida I, Aklillu E, Kawanishi C, Bertilsson L, Agren H (2007) Monoamine metabolites level in CSF is related to the 5-HTT gene polymorphism in treatment-resistant depression. Neuropsychopharmacology 32(10):2143–2151CrossRefPubMedGoogle Scholar
  28. Limson R, Goldman D, Roy A, Lamparski D, Ravitz B, Adinoff B et al (1991) Personality and cerebrospinal fluid monoamine metabolites in alcoholics and controls. Arch Gen Psychiatry 48(5):437–441PubMedGoogle Scholar
  29. Linnoila M, Virkkunen M, Scheinin M, Nuutila A, Rimon R, Goodwin FK (1983) Low cerebrospinal fluid 5-hydroxyindoleacetic acid concentration differentiates impulsive from nonimpulsive violent behavior. Life Sci 33(26):2609–2614CrossRefPubMedGoogle Scholar
  30. Mann JJ, McBride PA, Brown RP, Linnoila M, Leon AC, DeMeo M et al (1992) Relationship between central and peripheral serotonin indexes in depressed and suicidal psychiatric inpatients. Arch Gen Psychiatry 49(6):442–446PubMedGoogle Scholar
  31. Mehlman PT, Higley JD, Faucher I, Lilly AA, Taub DM, Vickers J et al (1994) Low CSF 5-HIAA concentrations and severe aggression and impaired impulse control in nonhuman primates. Am J Psychiatry 151(10):1485–1491PubMedGoogle Scholar
  32. Moller SE, Mortensen EL, Breum L, Alling C, Larsen OG, Boge-Rasmussen T et al (1996) Aggression and personality: association with amino acids and monoamine metabolites. Psychol Med 26(2):323–331CrossRefPubMedGoogle Scholar
  33. Placidi GP, Oquendo MA, Malone KM, Huang YY, Ellis SP, Mann JJ (2001) Aggressivity, suicide attempts, and depression: relationship to cerebrospinal fluid monoamine metabolite levels. Biol Psychiatry 50(10):783–791CrossRefPubMedGoogle Scholar
  34. Post RM, Kotin J, Goodwin FK, Gordon EK (1973) Psychomotor activity and cerebrospinal fluid amine metabolites in affective illness. Am J Psychiatry 130(1):67–72PubMedGoogle Scholar
  35. Prochazka H, Agren H (2003) Self-rated aggression and cerebral monoaminergic turnover. Sex differences in patients with persistent depressive disorder. Eur Arch Psychiatry Clin Neurosci 253(4):185–192CrossRefPubMedGoogle Scholar
  36. Sher L, Mann JJ, Traksman-Benz L, Winchel R, Huang YY, Fertuck E, Stanley BH (2006a) Lower cerebrospinal fluid homovanillic acid levels in depressed suicide attempters. J Affective Disorders 90:83–89CrossRefGoogle Scholar
  37. Sher L, Carballo JJ, Grunebaum MF, Burke AK, Zalsman G, Huang YY et al (2006b) A prospective study of the association of cerebrospinal fluid monoamine metabolite levels with lethality of suicide attempts in patients with bipolar disorder. Bipolar Disord 8(5 Pt 2):543–550Google Scholar
  38. Soderstrom H, Blennow K, Manhem A, Forsman A (2001) CSF studies in violent offenders. I. 5-HIAA as a negative and HVA as a positive predictor of psychopathy. J Neural Transm 108(7):869–878CrossRefPubMedGoogle Scholar
  39. Spielberger CD (1996) State-trait anger expression inventory: professional manual. Psychological Assessment Resources, Inc, Odessa, FLGoogle Scholar
  40. Stanley B, Molcho A, Stanley M, Winchel R, Gameroff MJ, Parsons B et al (2000) Association of aggressive behavior with altered serotonergic function in patients who are not suicidal. Am J Psychiatry 157(4):609–614CrossRefPubMedGoogle Scholar
  41. van der Vegt BJ, Lieuwes N, Cremers TI, de Boer SF, Koolhaas JM (2003) Cerebrospinal fluid monoamine and metabolite concentrations and aggression in rats. Horm Behav 44(3):199–208CrossRefPubMedGoogle Scholar
  42. Virkkunen M, Nuutila A, Goodwin FK, Linnoila M (1987) Cerebrospinal fluid monoamine metabolite levels in male arsonists. Arch Gen Psychiatry 44(3):241–247PubMedGoogle Scholar
  43. Virkkunen M, De Jong J, Bartko J, Goodwin FK, Linnoila M (1989) Relationship of psychobiological variables to recidivism in violent offenders and impulsive fire setters. A follow-up study. Arch Gen Psychiatry 46(7):600–603PubMedGoogle Scholar
  44. Virkkunen M, Rawlings R, Tokola R, Poland RE, Guidotti A, Nemeroff C et al (1994) CSF biochemistries, glucose metabolism, and diurnal activity rhythms in alcoholic, violent offenders, fire setters, and healthy volunteers. Arch Gen Psychiatry 51(1):20–27PubMedGoogle Scholar
  45. Wolf WA, Youdim MB, Kuhn DM (1985) Does brain 5-HIAA indicate serotonin release or monoamine oxidase activity? Eur J Pharmacol 109(3):381–387CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  1. 1.Clinical Neuroscience Research Unit, Department of Psychiatry and Behavioral Neuroscience, Pritzker School of MedicineThe University of ChicagoChicagoUSA

Personalised recommendations