Points that Need Attention in Early Auditory Information Processing Research in Schizophrenia

To the Editor: With great interest we read the priority data letter written by Dr. Joshi and colleagues, reporting that anticholinergic medication burden aggregated from all medications is associated with diminished MMN and P3a response (1). We appreciate Dr. Joshi’s efforts in evaluating this difficult body of literature, and we do believe revitalizing early auditory information processing (EAIP) research will provide gain on our knowledge of neuroscience in schizophrenia. Nevertheless, we would like to highlight two points regarding the conclusion.

The first point is the effect of relapse and illness duration. There is no doubt that MMN/P3a abnormalities existed across the illness course of schizophrenia, as the magnitudes between controls to at risk subjects to recent-onset schizophrenia to chronic schizophrenia (2). Also, recent literature revealed that relapses in schizophrenia contribute to treatment resistance (3, 4), while cortical deficits are associated with an increased likelihood of treatment resistance (5). As in the COGS-2 study, the duration of illness is 23.8 years (±6.9 years) and number of hospitalizations is 7.3 (±9.7) (6). However, although the multiple regression model included the Penn Computerized Neurocognitive Battery Global Cognition, chlorpromazine equivalents, scale of function, and symptom score, the distribution of duration of illness and number of hospitalizations were not demonstrated in Table 1 (1). Is it possible that “higher Anticholinergic Cognitive Burden score” is actually a surrogate measure of underlying longer illness duration, more relapses, and more treatment-resistance, which were associated with reduction in magnitude of both MMN and P3a?

Furthermore, Andreasen et al. advocated the importance of a cumulative value measured in dose-years in order to compare lifetime exposure to antipsychotics (7). Likewise, accumulated exposure, including different dosages of the same medication (e.g., lurasidone 160 vs. 40mg) and longitudinal exposure, should be fully considered in order to calculate the effect of anticholinergic medication burden on EAIP.