Original Investigation


, 203:53

First online:

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

  • Michael S. McCloskeyAffiliated withDepartment of Psychiatry, University of Chicago Email author 
  • , Dror Ben-ZeevAffiliated withDepartment of Psychology, Illinois Institute of Technology
  • , Royce LeeAffiliated withDepartment of Psychiatry, University of Chicago
  • , Mitchell E. BermanAffiliated withDepartment of Psychology, University of Southern Mississippi
  • , Emil F. CoccaroAffiliated withDepartment of Psychiatry, University of Chicago

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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.


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.


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.


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


Self-aggression Serotonin Tryptophan depletion Intermittent explosive disorder