Skip to main content
SpringerLink
Log in

Acute tryptophan depletion and self-injurious behavior in aggressive patients and healthy volunteers

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

Rationale

An association between serotonin (5-HT) activity and self-injurious (i.e., self-aggressive) behavior across the spectrum of lethality (from self-mutilation through completed suicide) is a well-replicated finding. Studies to date, however, have relied on nonexperimental designs to examine this relationship, limiting the causal inferences that can be drawn about the role of 5-HT in self-aggressive behavior.

Objective

Examine the effect of experimentally altered 5-HT activity (via dietary tryptophan depletion) on self-aggressive behavior among adults with and without intermittent explosive disorder (IED). Individuals with a marked history of aggression, such as those with IED, are characterized by compromised 5-HT and heightened risk for self-aggression, making this a population of interest for examining the proposed relations.

Materials and methods

IED patients (n = 16) and healthy controls (n = 16) received a tryptophan depletion and a placebo drink on separate days at least 1 week apart. Self-aggressive behavior was assessed on both study days using a well-validated laboratory-based behavioral assessment with self-aggression defined as the intensity of shock self-administered.

Results

Tryptophan depletion facilitated selection of more intense shocks, on average, in both groups. Patients with IED were also more self-aggressive overall than healthy volunteers. No IED by drink condition interactions were found.

Conclusion

Experimentally lowered 5-HT bioavailability enhances overall self-injurious behavior irrespective of aggression history.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

Notes

  1. Complete VAS data was available from 26 (15 control and 11 IED) of the 28 subjects who completed the SAP. The two remaining subjects failed to complete the VAS for at least one time point.

References

  • Arango V, Ernsberger P, Marzuk PM, Chen JS, Tierney H, Stanley M, Reis DJ, Mann JJ (1990) Autoradiographic demonstration of increased serotonin 5-HT2 and beta-adrenergic receptor binding sites in the brain of suicide victims. Arch Gen Psychiatry 47:1038–1047

    PubMed  CAS  Google Scholar 

  • Arora RC, Meltzer HY (1989) Serotonergic measures in the brains of suicide victims: 5-HT2 binding sites in the frontal cortex of suicide victims and control subjects. Am J Psychiatry 146:730–736

    PubMed  CAS  Google Scholar 

  • Berman ME, Walley JC (2003) Imitation of self-aggressive behavior: an experimental test of the contagion hypothesis. J Appl Soc Psychol 33:1036–1057

    Article  Google Scholar 

  • Berman ME, Jones GD, McCloskey MS (2005) The effects of diazepam on human self-aggressive behavior. Psychopharmacology (Berl) 178:100–106

    Article  CAS  Google Scholar 

  • Bjork JM, Dougherty DM, Moeller FG, Swann AC (2000) Differential behavioral effects of plasma tryptophan depletion and loading in aggressive and nonaggressive men. Neuropsychopharmacology 22:357–369

    Article  PubMed  CAS  Google Scholar 

  • Boldrini M, Underwood MD, Mann JJ, Arango V (2005) More tryptophan hydroxylase in the brainstem dorsal raphe nucleus in depressed suicides. Brain Res 1041:19–28

    Article  PubMed  CAS  Google Scholar 

  • Bond AJ, Wingrove J, Critchlow DG (2001) Tryptophan depletion increases aggression in women during the premenstrual phase. Psychopharmacology (Berl) 156:477–480

    Article  CAS  Google Scholar 

  • Briere J, Gil E (1998) Self-mutilation in clinical and general population samples: prevalence, correlates, and functions. Am J Orthopsychiatry 68:609–620

    Article  PubMed  CAS  Google Scholar 

  • Brown GL, Ebert MH, Goyer PF, Jimerson DC, Klein WJ, Bunney WE, Goodwin FK (1982) Aggression, suicide, and serotonin: relationships to CSF amine metabolites. Am J Psychiatry 139:741–746

    PubMed  CAS  Google Scholar 

  • Brown MZ, Comtois KA, Linehan MM (2002) Reasons for suicide attempts and nonsuicidal self-injury in women with borderline personality disorder. J Abnorm Psychol 111:198–202

    Article  PubMed  Google Scholar 

  • Carpenter LL, Anderson GM, Pelton GH, Gudin JA, Kirwin PD, Price LH, Heninger GR, McDougle CJ (1998) Tryptophan depletion during continuous CSF sampling in healthy human subjects. Neuropsychopharmacology 19:26–35

    Article  PubMed  CAS  Google Scholar 

  • CDC (2005) Web-based Injury Statistics Query and Reporting System (WISQARS). Available at http://www.cdc.gov/ncipc/wisqars/

  • Cleare AJ, Bond AJ (1995) The effect of tryptophan depletion and enhancement on subjective and behavioural aggression in normal male subjects. Psychopharmacology (Berl) 118:72–81

    Article  CAS  Google Scholar 

  • Coccaro EF (2003) Intermittent explosive disorder. In: Coccaro EF (ed) Aggression: psychiatric assessment and treatment. Marcel Dekker, New York, pp 149–199

    Google Scholar 

  • Coccaro EF, Kavoussi RJ (1997) Fluoxetine and impulsive aggressive behavior in personality-disordered subjects. Arch Gen Psychiatry 54:1081–1088

    PubMed  CAS  Google Scholar 

  • Comtois KA (2002) A review of interventions to reduce the prevalence of parasuicide. Psychiatr Serv 53:1138–1144

    Article  PubMed  Google Scholar 

  • Fava M, Rosenbaum JF, Pava JA, McCarthy MK, Steingard RJ, Bouffides E (1993) Anger attacks in unipolar depression, part 1: clinical correlates and response to fluoxetine treatment. Am J Psychiatry 150:1158–1163

    PubMed  CAS  Google Scholar 

  • Favazza AR (1998) The coming of age of self-mutilation. J Nerv Ment Dis 186:259–268

    Article  PubMed  CAS  Google Scholar 

  • First MB, Gibbons M, Spitzer RL, Williams JBW (1996) User’s guide for the SCID-I (Research Version). Biometrics Research, Biometrics Research

  • Goveas JS, Csernansky JG, Coccaro EF (2004) Platelet serotonin content correlates inversely with life history of aggression in personality-disordered subjects. Psychiatry Res 126:23–32

    Article  PubMed  CAS  Google Scholar 

  • Gratz KL (2001) Measurement of deliberate self-harm: preliminary data on the deliberate self-harm inventory. J Psychopathol Behav Assess 23:253–263

    Article  Google Scholar 

  • Gross-Isseroff R, Biegon A, Voet H, Weizman A (1998) The suicide brain: a review of postmortem receptor/transporter binding studies. Neurosci Biobehav Rev 22:653–661

    Article  PubMed  CAS  Google Scholar 

  • Gunnell D, Shepherd M, Evans M (2000) Are recent increases in deliberate self-harm associated with changes in socio-economic conditions? An ecological analysis of patterns of deliberate self-harm in Bristol 1972–3 and 1995–6. Psychol Med 30:1197–1203

    Article  PubMed  CAS  Google Scholar 

  • Joiner TE (2005) Why people die by suicide. Harvard University Press, Cambridge

    Google Scholar 

  • Joiner TE Jr, Johnson F, Soderstrom K (2002) Association between serotonin transporter gene polymorphism and family history of attempted and completed suicide. Suicide Life Threat Behav 32:329–332

    Article  PubMed  Google Scholar 

  • Keilp JG, Gorlyn M, Oquendo MA, Brodsky B, Ellis SP, Stanley B, John Mann J (2006) Aggressiveness, not impulsiveness or hostility, distinguishes suicide attempters with major depression. Psychol Med 36:1779–1788

    Article  PubMed  Google Scholar 

  • Kidd SA, Carroll MR (2007) Coping and suicidality among homeless youth. J Adolesc 30(2):283–296 (Apr)

    Article  PubMed  Google Scholar 

  • Kisiel CL, Lyons JS (2001) Dissociation as a mediator of psychopathology among sexually abused children and adolescents. Am J Psychiatry 158:1034–1039

    Article  PubMed  CAS  Google Scholar 

  • Klein DN, Ouimette PC, Kelly HS, Ferro T, Riso LP (1994) Test–retest reliability of team consensus best-estimate diagnoses of axis I and II disorders in a family study. Am J Psychiatry 151:1043–1047

    PubMed  CAS  Google Scholar 

  • LeMarquand DG, Benkelfat C, Pihl RO, Palmour RM, Young SN (1999) Behavioral disinhibition induced by tryptophan depletion in nonalcoholic young men with multigenerational family histories of paternal alcoholism. Am J Psychiatry 156:1771–1779

    PubMed  CAS  Google Scholar 

  • Lester D (1995) The concentration of neurotransmitter metabolites in the cerebrospinal fluid of suicidal individuals: a meta-analysis. Pharmacopsychiatry 28:45–50

    Article  PubMed  CAS  Google Scholar 

  • Linehan MM, Armstrong HE, Suarez A, Allmon D, Heard HL (1991) Cognitive-behavioral treatment of chronically parasuicidal borderline patients. Arch Gen Psychiatry 48:1060–1064

    PubMed  CAS  Google Scholar 

  • Lopez-Ibor JJ Jr, Saiz-Ruiz J, Perez de los Cobos JC (1985) Biological correlations of suicide and aggressivity in major depressions (with melancholia): 5-hydroxyindoleacetic acid and cortisol in cerebral spinal fluid, dexamethasone suppression test and therapeutic response to 5-hydroxytryptophan. Neuropsychobiology 14:67–74

    Article  PubMed  Google Scholar 

  • Mann JJ, Waternaux C, Haas GL, Malone KM (1999) Toward a clinical model of suicidal behavior in psychiatric patients. Am J Psychiatry 156:181–189

    PubMed  CAS  Google Scholar 

  • Mann JJ, Huang YY, Underwood MD, Kassir SA, Oppenheim S, Kelly TM, Dwork AJ, Arango V (2000) A serotonin transporter gene promoter polymorphism (5-HTTLPR) and prefrontal cortical binding in major depression and suicide. Arch Gen Psychiatry 57:729–738

    Article  PubMed  CAS  Google Scholar 

  • Marsh DM, Dougherty DM, Moeller FG, Swann AC, Spiga R (2002) Laboratory-measured aggressive behavior of women: acute tryptophan depletion and augmentation. Neuropsychopharmacology 26:660–671

    Article  PubMed  CAS  Google Scholar 

  • McCloskey MS, Berman ME (2003) Alcohol intoxication and self-aggressive behavior. J Abnorm Psychol 112:306–311

    Article  PubMed  Google Scholar 

  • McCloskey MS, Coccaro EF (2003) Questionnaire and interview measures of aggression in adults. In: Coccaro EF (ed) Aggression: psychiatric assessment and treatment. Marcel Dekker, New York, pp 167–193

    Google Scholar 

  • McCloskey MS, Berman ME, Noblett KL, Coccaro EF (2006) Intermittent explosive disorder-integrated research diagnostic criteria: convergent and discriminant validity. J Psychiatr Res 40:231–242

    Article  PubMed  Google Scholar 

  • McCloskey MS, Ben-Zeev D, Lee R, Coccaro EF (2008a) Prevalence of suicidal and self-injurious behavior among subjects with intermittent explosive disorder. Psychiatry Res 158:248–250

    Article  PubMed  Google Scholar 

  • McCloskey MS, Lee R, Berman ME, Noblett KL, Coccaro EF (2008b) The relationship between impulsive verbal aggression and intermittent explosive disorder. Aggress Behav 34:51–60

    Article  PubMed  Google Scholar 

  • Miller MD, Ferris DG (1993) Measurement of subjective phenomena in primary care research: the visual analogue scale. Fam Pract Res J 13:15–24

    PubMed  CAS  Google Scholar 

  • Moeller FG, Dougherty DM, Swann AC, Collins D, Davis CM, Cherek DR (1996) Tryptophan depletion and aggressive responding in healthy males. Psychopharmacology (Berl) 126:97–103

    Article  CAS  Google Scholar 

  • New AS, Trestman RL, Mitropoulou V, Benishay DS, Coccaro E, Silverman J, Siever LJ (1997) Serotonergic function and self-injurious behavior in personality disorder patients. Psychiatry Res 69:17–26

    Article  PubMed  CAS  Google Scholar 

  • Nishizawa S, Benkelfat C, Young SN, Leyton M, Mzengeza S, de Montigny C, Blier P, Diksic M (1997) Differences between males and females in rates of serotonin synthesis in human brain. Proc Natl Acad Sci U S A 94:5308–5313

    Article  PubMed  CAS  Google Scholar 

  • Nock MK, Prinstein MJ (2004) A functional approach to the assessment of self-mutilative behavior. J Consult Clin Psychol 72(5):885–890 (Oct)

    Article  PubMed  Google Scholar 

  • Pfohl B, Blum N, Zimmerman M (1995) Structured clinical interview for DSM-IV personality. In: Pfohl B, Blum N, Zimmerman M (eds) Structured clinical interview for DSM-IV personality. University of Iowa College of Medicine, Iowa City

    Google Scholar 

  • Pihl RO, Young SN, Harden P, Plotnick S, Chamberlain B, Ervin FR (1995) Acute effect of altered tryptophan levels and alcohol on aggression in normal human males. Psychopharmacology (Berl) 119:353–360

    Article  CAS  Google Scholar 

  • Roy-Byrne P, Post RM, Rubinow DR, Linnoila M, Savard R, Davis D (1983) CSF 5HIAA and personal and family history of suicide in affectively ill patients: a negative study. Psychiatry Res 10:263–274

    Article  PubMed  CAS  Google Scholar 

  • Salzman C, Wolfson AN, Schatzberg A, Looper J, Henke R, Albanese M, Schwartz J, Miyawaki E (1995) Effect of fluoxetine on anger in symptomatic volunteers with borderline personality disorder. J Clin Psychopharmacol 15:23–29

    Article  PubMed  CAS  Google Scholar 

  • Spitzer RL, Endicott J, Robins E (1978) Research diagnostic criteria: rationale and reliability. Arch Gen Psychiatry 35:773–782

    PubMed  CAS  Google Scholar 

  • Stockmeier CA (2003) Involvement of serotonin in depression: evidence from postmortem and imaging studies of serotonin receptors and the serotonin transporter. J Psychiatr Res 37:357–373

    Article  PubMed  Google Scholar 

  • Traskman L, Asberg M, Bertilsson L, Sjostrand L (1981) Monoamine metabolites in CSF and suicidal behavior. Arch Gen Psychiatry 38:631–636

    PubMed  CAS  Google Scholar 

  • Walderhaug E, Lunde H, Nordvik JE, Landro NI, Refsum H, Magnusson A (2002) Lowering of serotonin by rapid tryptophan depletion increases impulsiveness in normal individuals. Psychopharmacology (Berl) 164:385–391

    Article  CAS  Google Scholar 

  • Yen S, Shea MT, Sanislow CA, Grilo CM, Skodol AE, Gunderson JG, McGlashan TH, Zanarini MC, Morey LC (2004) Borderline personality disorder criteria associated with prospectively observed suicidal behavior. Am J Psychiatry 161:1296–1298

    Article  PubMed  Google Scholar 

  • Zlotnick C, Mattia JI, Zimmerman M (1999) Clinical correlates of self-mutilation in a sample of general psychiatric patients. J Nerv Ment Dis 187:296–301

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank Bing Chen, Damien McCormick, and Adam Strohm for their technical contributions. This study was supported in part by the Guggenheim Foundation (Dr. Royce Lee) and NIH K23MH073721 (Michael McCloskey, Ph.D.).

Author information

Authors and Affiliations

  1. Department of Psychiatry, University of Chicago, 5841 South Maryland Avenue, MC 3077, Chicago, IL, 60637, USA

    Michael S. McCloskey, Royce Lee & Emil F. Coccaro

  2. Department of Psychology, Illinois Institute of Technology, Chicago, IL, 60616, USA

    Dror Ben-Zeev

  3. Department of Psychology, University of Southern Mississippi, Hattiesburg, MS, 39406, USA

    Mitchell E. Berman

Authors
  1. Michael S. McCloskey
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dror Ben-Zeev
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Royce Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mitchell E. Berman
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Emil F. Coccaro
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael S. McCloskey.

Rights and permissions

Reprints and permissions

About this article

Cite this article

McCloskey, M.S., Ben-Zeev, D., Lee, R. et al. Acute tryptophan depletion and self-injurious behavior in aggressive patients and healthy volunteers. Psychopharmacology 203, 53–61 (2009). https://doi.org/10.1007/s00213-008-1374-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-008-1374-6

Keywords

Search

Navigation