Compared with patients in the appendicitis group, those in the methamphetamine cohort may have died at a higher rate during follow-up or had lower rates of health care insurance and, as a result, less access to medical care—two factors that could have led to an underestimation of the incidence rate of schizophrenia in our analyses of the methamphetamine and appendicitis groups. In addition, the mortality rates of the drug groups may have differed, and the lack of linked death records in our study may have introduced bias into our comparisons between the methamphetamine group and the other drug cohorts. Also, our identification of incident schizophrenia cases relied on inpatient admissions, an approach that would not have captured individuals with schizophrenia diagnosed in other settings. Nonetheless, a systematic review of the incidence of schizophrenia found that detection of schizophrenia outcomes across studies did not differ significantly by method of case ascertainment (e.g., use of hospital records, face-to-face interviews, and community based surveys) (18).
Diagnostic validity is a significant concern, especially given the absence of a clear etiopathogenetic understanding of schizophrenia (32). In the United States, clinical
diagnoses of schizophrenia during the 1990–2000 period would have been guided by the criteria established by APA (DSM-III-R from 1990 to 1994 and DSM-IV from 1994 to 2000), which in turn would be translated to an ICD-9-CM diagnosis for coding purposes. The use of “crosswalk” documents (33) helping coders determine the ICD-9-CM code corresponding to the DSM diagnosis makes it likely that DSM-III-R and DSM-IV clinical diagnoses of schizophrenia would be similarly coded in the ICD-9 classification. Both systems seek to distinguish primary psychotic disorders such as schizophrenia from drug-induced psychotic disorders. In the absence of independent chart reviews, however, there is uncertainty as to whether diagnoses of schizophrenia were justified or whether patients
were correctly assessed as not having schizophrenia at study entry. However, our supplemental analyses, which ensured that individuals had at least a 2-year period without any psychosis-related inpatient events prior to their index admission, limits to some extent the possibility of reverse causality. Also, we cannot confirm that patients
with a schizophrenia diagnosis were assessed over a prolonged drug-free interval to exclude a drug-induced psychotic state.