Regional Cerebral Glucose Metabolism in Never-Medicated Patients With Schizophrenia

Campbell Clark, PhD1, Lili Kopala, MD2, David K Li, MD3, Trevor Hurwitz, MD4

Objective: The purpose of this study was to assess regional cerebral glucose metabolism in  patients with schizophrenia who had never received antipsychotic medication and whose olfactory identification ability had been assessed. Two hypotheses were examined. First, the patients were compared with normal controls to determine whether differences in regional cerebral metabolism were apparent. Second, regional rates of metabolism were correlated with olfactory ability and the relation between them determined.
Methods: The patient (n = 26) and control (n = 32) subjects were scanned at rest using positron emission tomography (PET) after administration of  18F-fluorodeoxyglucose (FDG). In addition, the University of Pennsylvania Smell Identification Test was administered to each patient.
Results: Patients with schizophrenia had reduced rates of glucose metabolism in the right and left thalamus that reached significance if not corrected for multiple comparisons. However, if a Bonferroni correction was applied over the 27 regions of interest, the differences were not significant. Scores on the Smell Identification Test were negatively correlated with 8 regions of interest. When scores were analyzed using multiple regression, the left frontal cortex and the medial parietal cortex were significant predictors.
Conclusions: The finding of reduced metabolism in the thalami is consistent with some of the previous literature, whereas the negative correlations between specific regions and olfactory function are not consistent with studies using activation paradigms.

(Can J Psychiatry 2001;46:340-345)

Key Words: schizophrenia, cerebral glucose metabolism, olfaction

Since Bradley found that male patients with psychosis treated with neuroleptics had greater olfactory sensitivity to androstenone than normal controls (1), several studies have examined olfactory functions in patients with schizophrenia. Although Iseroff could not replicate Bradley’s finding using isoamyl acetate (2), studies assessing olfactory identification using the University of Pennsylvania Smell Identification Test (UPSIT) (3) have found differences between patients with schizophrenia and controls (4–8). This effect appears to be unrelated to neuroleptic medication per se because, in these studies, controls were often treated with neuroleptics (4), or medications had been withdrawn (8). Brewer and others concluded that “These findings could not be explained adequately by impaired peripheral innervation,

Manuscript received March 2000, revised, and accepted March 2001.
1 Professor, Department of Psychiatry, University of British Columbia, Vancouver, British Columbia.
2 Professor, Department of Psychiatry, Dalhousie University, Halifax, Nova Scotia.
3 Professor, Department of Radiology, University of British Columbia , Vancouver, British Columbia.
4 Clinical Professor, Department of Psychiatry, University of British Columbia, Vancouver, British Columbia.
Address for correspondence: Dr C Clark, Department of Psychiatry, University of British Columbia, 2255 Wesbrook Mall, Vancouver, BC  V6T 2A1
e-mail: cmblclrk@interchange.ubc.ca

fever, nasal obstruction, smoking, habituation to odours, or the drying effects of medication” (9, p 1022). Further, they and others (10) suggest that this deficit reflects dysfunction of central, not peripheral, mechanisms. Kopala and coworkers found that olfactory agnosia (that is, normal sensitivity to odours but impaired identification) was confined almost entirely to male patients with schizophrenia, of whom approximately 50% were affected (11,12). Kopala’s findings are of import because they suggest that the olfactory agnosia is confined to a specific subgroup of male patients with schizophrenia. The presence of this subgroup may explain the variability in the results of different studies due to differences in sample make-up (for example, the relative numbers of men and women).

The reasons for examining olfactory identification in patients with schizophrenia are twofold. First, the UPSIT is a well-standardized psychometric instrument where most (80% to 90%) normal individuals, aged 21 to 50 years, score 87% or higher (that is, 35 or more of 40 possible responses are correct). Because most normal subjects find the task relatively easy, the test is untimed, and the items may be repeated by the examiner if the subject is inattentive. Consequently, many of the potential confounds associated with deficits in cognitive processes in schizophrenia may be reduced, if not eliminated. Hence, one may obtain a reasonable estimate of true performance unbiased by potential secondary influences. The second

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