Acute d-Amphetamine Challenge in Schizophrenia: Effects on Cerebral Glucose Utilization and Clinic Symptomatology Adam Wolkin, Michael Sanfilipo, Burton Angrist, Erica Duncan, Susan Wieland, Alfred P. Wolf, Jonathan D. Brodie, Thomas B. Cooper, Eugene Laska, and John P. Rotrosen The effects of d-amphetamine (0.5 mg/kg orally) on regional cerebral glucose utilization were measured with positron emission tomography (PET) in 17 schizophrenics (along with a pla- cebo-control group of an additional six schizophrenic patients). The acute d-amphetamine challenge tended to decrease glucose utilization throughout much of the brain, with a regional effect that was statistically significant in the left temporal cortex. There was no apparepzt relationship between the effects of amphetamine-induced changes in regional cerebral metabo- lism and psychotic symptom exacerbation. An exploratory analysis suggested that features characteristic of Crow's type II syndrome were significant predictors of cerebral hyporespon- sivity to stimulant challenge, however. Key Words: Schizophrenia, PET, cerebral metabolism, d-amphetamine, tempora! lobe Intrigue,ion Central nervous system (CNS) stimulants have been widely used as tools in the study of schizophrenia (Angfist and van Kammen 1984). Amphetamine psychosis has been pro- posed as a model of the disorder at least with respect to its florid, productive psychopathology (Snyder 1973; Connell From the Psychiatry Service, New York Veterans Administration Medical Center {AW.MS, BA, ED, SW. JPR); the Departmentof Psychiatry, New York Univer- sity Medical Center (AW, BA, ED. JDB, JPR); the Chemistry Department. Brookhaven National Laboratory (APW), New York, NY; and the Nathan Kline Institute.Orangeburg, NY ('rBC, EL). Address ;eptim requests to Dr. Adara Wolkin, New York VA Medical Center ( I 16A ), 423 East 23rd Street. New Yott~,NY, 10010. These studies were supported in part by the Department of Veterans Affairs. NIH grant NS-15638, and the U.S. Department of Energy, Office of Health and Environmental Research. Received November7, 1993: revised February23. 1994. IOK@. Ar..~4et ,~t ~i IO'/A) Dcyr.hc,tle ~yin.ptnm~ :ira @xac~r- bated in approximately 40% of schizophrenic patients after doses of CNS stimulams, which are ordinarily nonpsycho- togenic in normals (L~eberman et al 1987a; Janowsky et al 1973). Moreover, a gather consistent body of data suggests that patients who s~,cw such symptom exacerbation are at increased risk for acute relapse if not taking neuroleptics (van Kammen et al 1982; Angrist et al 1985; Lieberman et al 1987b). Very similar observations have been made for I- DOPA challenges in schizophrenics in regards to both symptom activation (Angrist et al 1973, garyura-Tobias et al ! 970) and relapse prediction (Davidson et al 1987). These findings have been interpreted as reflecting the importance of catecholamine dysregulation in both positive symptoms of schizophrenia and in acute relapse (Snyder 1973). This paradigm may be further utilized as a tool in the © 1994 Society of Biological Psychiatry 0006-3223/94/$07.00