Functional significance of COMT genotype in violent patients with schizophrenia

Catechol O-methyltransferase (COMT) is an enzyme that has an important role in dopamine metabolism. Preliminary data obtained elsewhere revealed an apparent association between allelic variations in genes related to COMT and psychiatric ratings of "risk for dangerousness" (which were in turn related to histories of drug and alcohol abuse, causing bodily harm, violent crime, and threatening behavior). Patients homozygous for the allele associated with relatively low COMT activity (the "AA" genotype) were rated as high or medium risk for dangerousness, while those homozygous for the high activity allele (the "GG" genotype) were rated as low risk. This protocol aims to confirm and extend these preliminary findings. A number of other specific catecholaminergic, dopaminergic and serotonergic candidate genes have been identified. The relationship between history of violence and antisocial behavior and these candidate genes will be examined in patients diagnosed with schizophrenia or schizoaffective disorder. Subjects will undergo venipuncture for the purpose of genotyping. Life history of aggression will be obtained by interviewing the patient and reviewing all available history. The functional significance of the COMT genotype will be investigated using functional magnetic resonance imaging (fMRI) techniques to determine differences in patterns of cognitive activations.