Brain serotonin transporter distribution in subjects with impulsive aggressivity: a positron emission study with [11C]McN 5652.
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 [(11)C]McN 5652.


METHODS
Ten individuals with impulsive aggression and 10 age- and sex-matched healthy comparison subjects underwent [(11)C]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 (V(3)'').


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 V(3)'' (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.
Frankle
W Gordon
WG
Department of Psychiatry, Columbia University College of Physicians and Surgeons, and the New York State Psychiatric Institute, 1051 Riverside Dr., Box 31, New York, NY 10032, USA. wf2004@columbia.edu
Lombardo
Ilise
I
New
Antonia S
AS
Goodman
Marianne
M
Talbot
Peter S
PS
Huang
Yiyun
Y
Hwang
Dah-Ren
DR
Slifstein
Mark
M
Curry
Susan
S
Abi-Dargham
Anissa
A
Laruelle
Marc
M
Siever
Larry J
LJ
D000328:Adult; D000374:Aggression / Q000523:psychology*; D001921:Brain / Q000378:metabolism*; D002250:Carbon Radioisotopes; D005260:Female; D007839:Functional Laterality; D006179:Gyrus Cinguli / Q000378:metabolism; D006801:Humans; D007175:Impulsive Behavior / Q000175:diagnosis* / Q000378:metabolism; D007546:Isoquinolines; D008279:Magnetic Resonance Imaging; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D049268:Positron-Emission Tomography / Q000706:statistics & numerical data; D012701:Serotonin / Q000378:metabolism; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D014018:Tissue Distribution
D002250:Carbon Radioisotopes; D007546:Isoquinolines; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C493230:SLC6A4 protein, human; D012702:Serotonin Antagonists; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; C058079:McN 5652