To the Editor: The study by Natalie D. Veen, M.D., and colleagues (1) found an association between cannabis use and younger age at onset of schizophrenia in male patients in a first-contact incidence study and recommended additional studies to examine this possible causal relationship. The authors considered three potential explanations for the association. Two of these explanations were as follows: cannabis use can "bring forward" the onset of a psychotic disorder in individuals who would have developed the disorder whether they had used cannabis or not, and cannabis use can cause schizophrenia in at least some individuals who would not have developed schizophrenia had they not used cannabis. However, as Dr. Veen and colleagues noted, there is scant epidemiological evidence to support these potential mechanisms (2).

A third explanation was that cannabis has no influence on age at onset and that the association between the two variables is simply because younger patients are more likely to use cannabis. This would seem to be a plausible explanation for two reasons. First, younger individuals at first contact would be expected to have a younger age at onset of a psychotic episode than older individuals. Second, younger age (and male gender) is a reliable demographic predictor of substance misuse in individuals with psychotic disorders as well as the general community (3). As a result, it should not be surprising that patients with a comparatively younger age at onset are at increased risk for the use of cannabis and other substances. Dr. Veen and colleagues argued that this explanation was not supported by their finding of a higher rate of cannabis use in the incidence cohort compared to members of the general population of similar age. However, this is not relevant to the fact that younger age is a robust risk factor for substance use in both clinical and community populations. Rather, it points to the need to better understand the high prevalence of substance misuse found in psychotic disorders. For example, the higher prevalence of cannabis use in the incidence cohort relative to the general population is likely to be partly due to the high proportion of male patients recruited into the study.

This appears to be a promising study that will inform our understanding of the onset and early course of psychotic disorders, and I hope that this comment will be a positive contribution to the interpretation of its findings.