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Modulation of Central Serotonin Affects Emotional Information Processing in Impulsive Aggressive Personality Disorder

Lee, Royce J. MD*; Gill, Andrew*; Chen, Bing MA*; McCloskey, Michael PhD; Coccaro, Emil F. MD*

Journal of Clinical Psychopharmacology: June 2012 - Volume 32 - Issue 3 - p 329–335
doi: 10.1097/JCP.0b013e31825368b7
Original Contributions

Background: The mechanistic model whereby serotonin affects impulsive aggression is not completely understood. The purpose of this study was to test the hypothesis that depletion of serotonin reserves by tryptophan depletion affects emotional information processing in susceptible individuals.

Methods: The effect of tryptophan (vs placebo) depletion on processing of Ekman emotional faces was compared in impulsive aggressive personality disordered, male and female adults with normal controls. All subjects were free of psychotropic medications, medically healthy, nondepressed, and substance free. Additionally, subjective mood state and vital signs were monitored.

Results: For emotion recognition, a significant interaction of Aggression × Drug × Sex (F1, 31 = 7.687, P = 0.009) was found, with male normal controls but not impulsive aggressive males showing increased recognition of fear. For intensity ratings of emotional faces, a significant interaction was discovered of Drug × Group × Sex (F1, 31 = 5.924, P = 0.021), with follow-up tests revealing that males with intermittent explosive disorder tended to increase intensity ratings of angry faces after tryptophan depletion. Additionally, tryptophan depletion was associated with increased heart rate in all subjects, and increased intensity of the subjective emotional state of “anger” in impulsive aggressive subjects.

Conclusions: Individuals with clinically relevant levels of impulsive aggression may be susceptible to effects of serotonergic depletion on emotional information processing, showing a tendency to exaggerate their impression of the intensity of angry expressions and to report an angry mood state after tryptophan depletion. This may reflect heightened sensitivity to the effects of serotonergic dysregulation, and suggests that what underlies impulsive aggression is either supersensitivity to serotonergic disturbances or susceptibility to fluctuations in central serotonergic availability.

From the *Clinical Neuroscience Research Unit, Department of Psychiatry, University of Chicago Pritzker School of Medicine, Chicago, IL; and †Department of Psychology, Temple University, Philadelphia, PA.

Received January 11, 2011; accepted after revision November 30, 2011.

Reprints: Royce J. Lee, MD, Clinical Neuroscience Research Unit, Department of Psychiatry, University of Chicago, 5841 South Maryland Ave, Chicago, IL 60637 (e-mail:

This study was made possible by a Young Investigator grant from the Harry Frank Guggenheim Foundation and by the support of the General Clinical Research Center of the University of Chicago, which is funded by grant number M01 RR000055 from the National Center for Research Resources of the National Institutes of Health. The experimental procedures were executed largely by Lauren McCabe, Bennet Barch, and Cara Van Wormer (research assistants); Cindy Bogue, RN (research nurse); and Mary Santos (senior research coordinator).

© 2012 Lippincott Williams & Wilkins, Inc.