The proposed studies are designed to evaluate 5-hydroxytryptophan transporter (5-HTT) binding of [S11C] McN5652 in midbrain and 5-HT2a receptor binding of [S11C] MDLIOO9O7 in orbital frontal cortex in 40 patients with impulsive aggressive personality disorders and 40 normal volunteer controls controlling for gender, age, season of the year, and other clinical/demographic variables. It is hypothesized that 5-HTT binding will be reduced in the impulsive aggressive personality disorder patients compared to normal controls, while 5-HT2a receptor binding will be increased in impulsive aggressive personality disorder patients compared to normal controls. These proposed studies would be the first to explicitly evaluate these components of the serotonergic system In vivo in impulsive aggressive personality disorder patients, but build on a large body of data regarding serotonergic abnormalities in impulsive aggression.
The specific aims of this proposal are to: I) Identify and clinically characterize 40 impulsive/aggressive personality disorder patients (20 males, 20 females) as defined by DSM-lV criteria in Methodsas well as 40 normal volunteer control subjects (20 males, 20 females) over four years, 2) Measure [S11C] McN5652binding by Positron Emission Tomography (PET) scan in the midbrain region of the impulsive aggressive personality disorder patients and the normal control comparison group, 3) Measure binding of [S11C] MDLIOO9O7 by PET scan in orbital frontal cortex of impulsive/aggressive personality disorder patients and the normal control comparison group. Secondary analyses include the correlation of ratings of impulsive aggression in the impulsive personality disorder cohort in relation to both the 5-HTT binding and the 5-HT2a receptor binding and the correlation of specific 5-HiT and 5-Hi2a receptor binding with polymorphisms of the 5-HTT and 5-HT2a receptor respectively obtained through other funding. The proposed study will enable a better understanding of the character of serotonergic dysfunction in impulsive/aggression.
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