Clozapine Response In Chronic Schizophrenia And Brain Morphology On MRI: A Preliminary Report

Abstract

Clozapine is a dibenzodiazepine atypical antipsychotic agent with demonstrated efficacy in treatment resistant and treatment intolerant schizophrenic populations (Kane 1988;Pickar 1992). Previous reports suggest clozapine's efficacy in schizophrenia may be related to morphologic abnormalities in lateral frontal and prefrontal cortices as measured on CT (Friedman 1991;Honer 1993) and MRI (Breier 1993). To examine this issue further, 18 chronic schizophrenic (DSM-III-R) patients (mean age 27 years, 89% male) who received standardized treatment with clozapine (mean duration of treatment = 30 months ± 19.43), underwent assessments for psychopathology (BPRS, CGI, SANS) and brain morphology with magnetic resonance imaging. MRIs were acquired using a gradient echo pulse sequence (3D flash) on a Siemens-Magneton (1.0 tesla) system. Images were analyzed under blind conditions by trained personnel using quantitative (total brain volume, interhemispheric fissure volume) and qualitative (evaluation of sulcal prominence, cerebral cortex, lateral ventricles, third ventricle, medial temporal lobe structures) measures. Data analyses examined the relationship between brain morphologic variables and measures of psychopathology at baseline and during clozapine treatment. Preliminary analyses to date have found no significant associations between the specific morphologic variables described above and treatment outcome. Mean severity of psychopathology at baseline was associated with increased interhemispheric fissure volume (r = 0.54,p = 0.02), due to positive symptom factors on the BPRS. These results mainly reflecting replicate previous findings of abnormal brain morphology being associated with poorer response to clozapine. Reasons may include differences in patient samples and the limited number of patients studied. This issue will be reexamined in the context of a larger patient sample as data become available.