Faculty Bibliography

Molecular imaging, the study of receptors, transporters and enzymes, as well as other cellular processes, has grown in recent years to be one of the most active neuroimaging areas. The application of single photon emission tomography (SPECT) and positron emission tomography (PET) techniques to the study of psychiatric illness has lead to increased understanding of disease processes as well as validated, in vivo, theories of illness etiology. Within the field of psychiatry these techniques have been applied most widely to the study of schizophrenia. Studies within schizophrenia are largely limited to either the dopamine or serotonin system. This is due in large part to the availability of suitable radiotracers as well as the current theories on the etiology of the illness. Two basic study designs are used when studying schizophrenia using molecular imaging and make up the majority of studies reviewed in this manuscript. The first type, termed "clinical studies," compares the findings from PET and SPECT studies in those with schizophrenia to normal controls in an attempt to understand the pathophysiology of the illness. The second study design, termed "occupancy studies," uses these techniques to enhance the understanding of the mechanism of action of the medications used in treating this illness. This review will focus on the findings of molecular imaging studies in schizophrenia, focusing, for the most part, on the serotonin and dopamine systems. Emphasis will be placed on how these findings and techniques are currently being used to inform the development of novel treatments for schizophrenia.

OBJECTIVE: The authors examined the relationship between treatment with clozapine and rates of arrest of psychotic outpatients with criminal histories. METHOD: Patients who had been given a DSM-IV psychotic diagnosis were selected from an urban outpatient clinic database. Background checks performed on 360 patients identified 165 (45.8%) with positive criminal histories in Massachusetts. The authors reviewed the charts of these patients to determine several variables, including whether and when they had received clozapine. A Poisson regression model was used to regress arrest rates against the variables of age, sex, onset of illness, birth cohort, and clozapine treatment. Risk ratios (i.e., percent change in arrest rates) were then calculated by computing the exponential of the Poisson regression coefficients. RESULTS: The 165 patients included in the analysis had a total of 1,126 arrests. The mean number of arrests was 6.8. Differences were found between the 65 patients who received clozapine and the 100 patients who did not in number of arrests, sex, and onset of illness. The regression revealed significantly higher arrest rate estimates associated with more recent birth cohort (4.8%) and with onset of illness (64.6%) and lower arrest rate estimates associated with higher levels of education (11.6%), receiving clozapine (32.6%), and receiving clozapine during specific periods of time (68.9%). CONCLUSIONS: Clozapine's effect on arrest rates in this group of patients is large enough to warrant further investigation. The data indicate that clozapine may reduce recidivism in subjects with criminal histories who are in need of antipsychotic medication.