Brain Serotonin Transporter Distribution in Subjects With Impulsive Aggressivity

A Positron Emission Study With [11C]McN 5652

  • Frankle, W. Gordon M.D.
  • Lombardo, Ilise M.D.
  • New, Antonia S. M.D.
  • Goodman, Marianne M.D.
  • Talbot, Peter S. M.D.
  • Huang, Yiyun Ph.D.
  • Hwang, Dah-Ren Ph.D.
  • Slifstein, Mark Ph.D.
  • Curry, Susan B.A.
  • Abi-Dargham, Anissa M.D.
  • Laruelle, Marc M.D.
  • Siever, Larry J. M.D.

  • Departments of Psychiatry and Radiology, Columbia University College of Physicians and Surgeons and the New York State Psychiatric Institute; the Psychiatric Service, Bronx Veterans Affairs Medical Center, Bronx, N.Y.; and the Department of Psychiatry, Mount Sinai School of Medicine, New York.

Address correspondence and reprint requests to Dr. Frankle, New York State Psychiatric Institute, 1051 Riverside Dr., Box 31, New York, NY 10032; [email protected] (e-mail).

Ms. Curry died in June 2004. The authors dedicate this paper in memory of her.

Supported in part by NIMH grants 1RO1 MH-63875, 5RO1 MH-56606, and 1-K02 MH-01603-01).

The authors thank Julie Arcement, Jennifer Bae, Ashlie Darr, Ingrid Gelbard-Strokes, Elizabeth Hackett, Kimchung Ngo, Chaka Peters, Nurat Quadri, Celeste Reinking, Norman Simpson, Lyudmila Savenkova, Kris Wolff, and Zohar Zephrani for their technical assistance.

Received Feb. 12, 2004; revision received April 23, 2004; accepted May 14, 2004.

American Journal of Psychiatry 162(5):p 915-923, May 2005.

Objective

The serotonin system is believed to play a role in modulating impulsivity and violence. Previous imaging studies have implicated the anterior cingulate and orbitofrontal cortex in impulsive aggression. This study evaluated regional serotonin transporter distribution in the brain of individuals with impulsive aggression by using positron emission tomography (PET) with the serotonin transporter PET radiotracer [11C]McN 5652.

Method

Ten individuals with impulsive aggression and 10 age- and sex-matched healthy comparison subjects underwent [11C]McN 5652 PET. All individuals were medication free at the time of scanning. Regional total distribution volumes were derived by using a one-tissue compartment kinetic model with arterial input function. Outcome measures of serotonin transporter availability included the binding potential and the specific-to-nonspecific partition coefficient (V3″).

Results

Serotonin transporter availability was significantly reduced in the anterior cingulate cortex of individuals with impulsive aggression compared with healthy subjects, as noted by differences in both binding potential (mean=3.1 ml/g [SD=1.9] versus 5.0 ml/g [SD=2.0], respectively) and V3″ (mean=0.15 [SD=0.09] versus 0.26 [SD=0.09]). In other regions examined, serotonin transporter density was nonsignificantly lower in individuals with impulsive aggression compared with healthy subjects.

Conclusions

Pathological impulsive aggressivity might be associated with lower serotonergic innervation in the anterior cingulate cortex, a region that plays an important role in affective regulation.

Copyright © 2005 American Psychiatric Association.