Blunted Change in Cerebral Glucose Utilization After Haloperidol Treatment in Schizophrenic Patients With Prominent Negative Symptoms

Wolkin, Adam MD
Sanfilipo, Michael MS
Duncan, Erica MD
Angrist, Burton MD
Wolf, Alfred P. PhD
Cooper, Thomas B. MA
Brodie, Jonathan D. PhD, MD
Laska, Eugene PhD
Rotrosen, John P. MD

Received May 18, 1995; revision received Oct. 30, 1995; accepted Nov. 9, 1995. From the Psychiatry Service, New York VA Medical Center; the Department of Psychiatry, New York University Medical Center, New York; the Chemistry Department, Brookhaven National Laboratory, Upton, N.Y.; and the Nathan Kline Institute, Orangeburg, N.Y. Address reprint requests to Dr Wolkin, New York VA Medical Center (116A), 423 East 23rd St., New York, NY 10010.
Supported in part by funds from the Department of Veterans Affairs, NIH grant NS-15638 from the National Institute of Neurological Disorders and Stroke, NIMH grant MII-42959, and funds from the U.S. Department of Energy, Office of Health and Environmental Research.
The authors thank Eric Peselow, Andrew Lautin, Elsa Bartlett, Joanna Fowler, Donald Warner, Payton King, Noelwah Netusil, Theodore Johnson, Collean Shea, Elizabeth Jellett, David Alexoff, David Schlyer, Robert Carciello, Babe Barrett, Morris Mcisner, and Joseph Wanderling for their help.

American Journal of Psychiatry 153(3):p 346-354, March 1996.

Objective

The purpose of this report was to determine 1) the effects of chronic haloperidol treatment on cerehral metabolism in schizophrenic patients, 2) the relation between negative symptoms and haloperidol-induced regional changes in cerebral glucose utilization, and 3) the relation between metabolic change and clinical anlipsychotic effect. Method: Cerebral glucose utilization, as determined by positron emission tomography (PET), was studied in 18 male schizophrenic subjects before and after chronic treatment with haloperidol at a standardized plasma level. Results: Overall, haloperidol caused a widespread decrease in absolute cerebral glucose metabolism, a relative decrease in prefrontal cortex glucose metabolism, and a relative increase in striatal metabolism. The cerebral metabolic response to haloperidol was blunted in patients with high pretreatment negative symptom scores. Conclusions: Taken together with the results from a previously reported PET study of the effects of an acute amphetamine challenge (in which 14 of the current subjects participated), these data suggest that the negative symptom complex is associated with diminished cerebral response to change in dopaminergic activity. This deficit cannot be solely accounted for by structural differences.

(Am J Psychiatry 1996; 153:346-354)