Effect of neuroleptics on altered cerebral glucose metabolism in schizophrenia
H. Szechtman, C. Nahmias, E. S. Garnett, G. Firnau, G. M. Brown, R. D. Kaplan and J. M. Cleghorn
Department of Neurosciences, McMaster University, Hamilton, Ontario, Canada.
This study examines whether the duration of treatment with antipsychotic
drugs influences the regional distribution of cerebral
[18F]2-fluoro-2-deoxy-D-glucose utilization as measured by positron
emission tomography. Two groups of schizophrenic patients are compared with
normal volunteers (n = 10). One group (n = 5) consisted of patients treated
for one year, and the second (n = 12) of patients medicated for four to 14
years (mean +/- SD duration, 7.4 +/- 3.4 years). The first group was also
examined before patients received their first dose ever of antipsychotic
medication. One year of medication was not sufficient to alter the
schizophrenic profile of cerebral cortical glucose activity but did elevate
activity of the corpus striatum. Medication for 7.4 years also did not
alter the schizophrenic pattern of frontal hyperactivity and posterior
hypoactivity, although deviations from control values appeared less marked
than after one year. On the other hand, in patients medicated for 7.4
years, there was perhaps an even greater increase in the activity of the
corpus striatum and of the thalamus. Thus, duration of exposure to
antipsychotic medication may affect the pattern of cerebral glucose
activity; possibly, even longer exposure may contribute to the
hypofrontality noted by others, although this can be confounded with the
duration of illness as a factor. In considering the biological significance
of the observed profile of cortical glucose activity, we introduce the
concept of cerebral metabolic tone. We suggest that a disturbance of this
tonus may account for some symptoms of schizophrenia and could be
consistent with the hypothesis of abnormal developmental changes in the
brains of schizophrenics.
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