The article by Shiloah et al. (1) in no way answers the question of whether the glucose dysregulation observed in patients with acute psychotic episodes is due to the stress of the psychosis. The design of this study has major flaws that make it impossible to draw any firm conclusions from the findings presented. First, the term “acute psychotic stress” is not defined by the authors and is certainly not found in the DSM-4 handbook as indicated by the authors. Furthermore, no diagnostic criteria are used to confirm the diagnoses of “chronic schizophrenia” or indeed “residual or paranoid schizophrenia.” Though we are told that patients with “acute psychotic stress” were hospitalized, we are also told on page 1463 that “All patients were well controlled before admission.” Exactly what this statement means is not explained.
Patients taking medications that could influence insulin or glucose activity were excluded. Yet we are given a list of medications in “Patients and study design” in the second point prefaced by “i.e.,” implying that the list given is complete. Yet what of other atypical and typical agents that have been alleged to induce glucose dysregulation? Leaving aside the issue of medication, no severity of illness or indeed abnormal movement scales are given, so we have no idea as to how sick these patients actually are. Instead we are told that a “subjective impression” of their “stress” was documented using a seven-point clinical global impression (CGI). The authors state that it is “similar to the Global Assessment Scale,” but there are no references provided that indicate it has been adequately validated. In contrast, in a recent study using DSM-4 criteria and well-validated scales (Brief Psychiatric Rating Scale and Schedule for the Assessment of Negative Symptoms & Abnormal Involuntary Movement Scale), we found no association between severity of illness or abnormal movements related to fasting insulin, glucose, or insulin resistance (2), indicating the acute presentation was not responsible for the glucose dysregulation observed in first episode, drug-naïve patients with schizophrenia.
In Table 1 we are told that that their mean ± SD age was 39 ± 10.5 years but the age range was 19–37 years. How can the average age be higher than the maximum age range given? The range of the BMI was from 16.0 to 40.1 kg/m2, which means that some patients were potentially anorexic and others were morbidly obese. Was it really appropriate to measure such metabolic parameters in patients with such vastly differing BMIs? Lastly, in Table 1 we are told that patients had a host of cardiovascular risk factors and diseases. Is it not likely that the insulin insensitivity and abnormal β-cell function was present many years before the time of admission as some of the “background diseases” are consequent upon having problems with glucose regulation?
Table 2 clearly shows that patients were most insulin sensitive on admission and following discharge, least sensitive with corresponding changes in β-cell function, and that fasting plasma glucose levels did not vary throughout the study, which would indicate that treatment with typical antipsychotic medication may have contributed to their findings. However, if on admission, patients were divided into “low and high” categories according to their CGI scores, significant differences began to emerge. The “low and high” scores were either ≤6 or >6 (the maximum being 7), respectively. Therefore, the authors compared the most extremely ill with all of the other patients. The cutoff figures were picked arbitrarily with no scientific reasons given for doing so. Furthermore, we were not told how many patients fit into each category. From a statistical perspective, the correlation coefficient for CGI and insulin was r = 0.37 and for CGI and fasting blood glucose was 0.47; the respective r2 values are 0.22 and 0.14, implying that 71% of the variance cannot be explained by these findings. Namely, that “acute psychotic stress” was not primarily responsible for their results. Indeed, we are told later in the results section that there was a negative correlation between insulin sensitivity and “psychotic stress” on admission, but we are not given any r value or indeed any indication of the numbers of patients in each group, making it impossible to judge what real significance these findings have.
The authors state in the conclusions that prestudy medications cannot explain their findings because atypical antipsychotics were not used. However, typical antipsychotics have been implicated in the abnormal glucose regulation seen in schizophrenia, as the authors themselves state. In addition, we are not told how long patients were free of their medications before admission, as certain intramuscular preparations can have effects for many months after their last administration. Finally, the importance of chronic stress as a potential pathogenetic mechanism in the development of type 2 diabetes in schizophrenia is evident; however, the results presented by Shiloah et al. (1) do not provide any evidence for acute stress causing such glucose dysregulation.
