Association between regional brain volumes and clozapine response in schizophrenia

John Lauriello, Daniel H. Mathalon, Margaret Rosenbloom, Edith V. Sullivan, William O. Faustman, David L. Ringo, Kelvin O. Lim, Adolf Pfefferbaum

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


Background: Clozapine has shown considerable therapeutic promise in the treatment of schizophrenia; however, the clinical risks and initial high treatment costs associated with its administration motivate the search to identify patients who will best respond. Neuroimaging studies have suggested that prefrontal sulcal prominence may be a predictor of nonresponsiveness. Methods: We used magnetic resonance imaging (MRI) to test whether volumes in any cortical regions of the brain were associated with symptom improvement with clozapine treatment. The 21 schizophrenic men studied were clinically evaluated during treatment with typical neuroleptics (baseline) and after a mean of 6.2 months treatment with clozapine (final dose 300-900, median = 562 mg/day). At least a 20% improvement on total Brief Psychiatric Rating Scale (BPRS) was seen in 47.6% of the schizophrenics. Clinical improvement was regressed on baseline differences in clinical severity, and the residual scores were related to MRI values. Results: Patients with larger anterior superior temporal lobe cerebrospinal fluid volumes (primarily sylvian fissure) showed greater improvement on total BPRS and withdrawal/retardation symptoms. Conclusions: Even schizophrenics with significant brain dysmorphology can have a positive clinical response to clozapine.

Original languageEnglish (US)
Pages (from-to)879-886
Number of pages8
JournalBiological psychiatry
Issue number12
StatePublished - Jun 15 1998

Bibliographical note

Funding Information:
This research was supported by Medical Research Service of the Department of Veterans Affairs, the National Institute of Mental Health (MH30854), the Norris Foundation, and Sandoz Pharmaceutical Corporation.


  • Brain
  • Clozapine
  • Magnetic resonance imaging
  • Schizophrenia
  • Treatment response


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