This proposal is for a supplement to our funded grant MH63875 """"""""Imaging 5-HT2a Receptors in Patients with Impulsive Aggression and Controls with MDL100907"""""""" which proposes measurement of binding of [11C]DASB to the serotonin transporter in cingulate cortex and other regions of interest in impulsive aggressive personality disordered patients. While the original submission for the currently funded study proposed measuring 5-HTT binding using [11 C]McN5652, this study was deleted as this compound was not sufficiently sensitive to measure 5-HTT binding in regions of interest in prefrontal cortex so that the final funded proposal only included measurement of the 5-HT2a receptor with MDL100907. Since the grant was approved, Dr. Laruelle and his colleagues at Columbia have completed extensive pilot studies of a more potent ligand at cortical sites [11C]DASB which they have studied in healthy volunteers and found to display more specific binding to cortical regions, including an almost two fold specificity for cingulate cortex, then the [11C]McN5652. Thus, the specific objectives of this supplemental study are to identify and recruit 20 impulsive personality disorder patients and 20 normal volunteer control subjects who will also be evaluated using [11C]MDL100907 binding to the 5-HT2a receptor over the last two years of this funded grant. The [11C]DASB binding would be compared between impulsive aggressive personality disorder patients in comparison groups with the primary region of interest being cingulate cortex but secondary regions include mid brain, amygdala, and thalamus controlling for gender, age, weight, season of the year, period of the menstrual cycle, and other clinical/demographic variables. Exploratory analysis will also evaluate whether 5-HTT number is inversely correlated with 5-HT2a receptor number, whether it is correlated with the degree of impulsive aggression and the degree of depression and whether it is significantly associated with allelic polymorphisms of the 5-HTT. ? ?
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