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.

Prodromal schizophrenia and atypical antipsychotic treatment.

Early recognition and intervention in psychosis is the focus of more intensive research. In this paper, we critically review the ideas that have emerged in this field. We also propose a model or hypothesis for testing in the prodromal phase of schizophrenia. Attention to practical and ethical issues, particularly with the use of atypical antipsychotics in one arm of the protocol, is addressed. Studies by Yung and Falloon describe prodromal intervention with psychosocial strategies and time-limited low potency neuroleptics, respectively, that suggest benefits of such a model. Although we have respect for the DSM system, this paper is written more from a Bleulerian than Kraepelinian perspective in that we emphasize affective, cognitive, and negative symptoms in addition to positive symptoms. The paper recognizes the strong conceptual disagreements implicit in this area stemming not only from Kraepelin and Bleuler but work from the 1930s by Cameron. The clinical research advocated is timely in that the atypicals are more congruent to the Bleulerian conception with a neurodevelopmental hypothesis of schizophrenia. We also have exciting new imaging and genetic technologies to refine our concepts of schizophrenia and its prodromal and premorbid phases.

Millon multiaxial personality patterns differentiate depressed and anxious outpatients.

Ninety-three patients, including 47 patients with Generalized Anxiety Disorder (GAD) and 46 patients with Major Depression (MD), were entered into recent clinical trials. Clinicians acknowledge that during the initial screening process, clear separation between depressed and anxious patients may be difficult. By using the DSM-IV criteria, the Hamilton Depression and Anxiety Scales, and a variety of other structured evaluations, patients were divided into the two diagnostic groups. The Millon Multiaxial Inventory (MCMI-III) was administered to all 93 patients as part of their initial assessment, but was not used in the diagnostic decision making process or in assignment to a particular clinical study. Upon completion of these studies, the Millon data were analyzed utilizing a cutoff score of 75, conforming to previous studies. Statistically significant differences in Millon personality patterns between MD and GAD patients included dependent, obsessive-compulsive, self-defeating, and borderline traits. Patients exhibiting dependent, self-defeating, and borderline patterns were statistically more likely to be included in clinical trials of MD rather than GAD. Also, patients with MD were more likely to disclose clinical information and exhibit self-critical behavior when compared to those with GAD. These results suggest that the MCMI-III may detect personality differences between anxious and depressed outpatients presenting for clinical trials.