Glucose metabolism in relation to schizophrenia and antipsychotic drug treatment

It has been reported in the earlier literature that many patients with psychoses had abnormalities in glucose metabolism as revealed by glucose tolerance testing. This observation is reinforced by the fact that the schizophrenic population appears to have about a 2-3-fold increased risk for Type II diabetes mellitus. However, some uncertainty remains about the relative risk value because there have been numerous case reports of patients who developed hyperglycemia and even Type II diabetes apparently as a consequence of treatment with antipsychotic drugs. Schizophrenic patients with abnormal glucose metabolism have a higher prevalence of drug-induced tardive dyskinesia than patients with a normal glucose profile. Treatment with the new atypical antipsychotics has a much lower risk of movement disorders; however, weight gain, hyperglycemia, and diabetes are emerging as significant side effects. Because glucose is essential for energy metabolism in neurons, any change in the effective glucose levels in brain that result from drug therapy may have significant clinical implications. It is not clear whether the glycemic state of schizophrenics contributes to their psychotic symptoms or modulates the incidence of drug side effects. Basic research shows that the drugs which cause hyperglycemia in patients appear to inhibit neuronal glucose transport which may partly explain their effects. This paper reviews the relevant literature in a preliminary attempt to understand the implications of such clinical findings in the light of basic research.