de la Fuente-Sandoval et al, (2011) recently reported that MRS-measured striatal glutamate is significantly higher in first-episode schizophrenia patients and ultra high-risk subjects compared with controls. They also report significant positive correlations between glutamate and NAA levels in striatum and cerebellum.

This theoretically motivated study of antipsychotic naïve patients is applauded for its potential to further our understanding of schizophrenia, but it is important to point out a critical limitation of the quantitative methods that appears to invalidate the conclusions. The authors have used the ‘absolute concentration’ values for metabolites generated by LCModel, which are listed in the first column of its output. Section 2.1 of the LCModel manual, version 6.2-3 (Provencher, 1993) specifically cautions against using these values in statistical analyses without first applying a unique correction factor to all metabolites from each MRS acquisition. The manual states that only if techniques such as waterscaling or creatine normalization are used, will the arbitrarily scaled absolute concentration data be meaningful. It appears that the authors used these values without applying one of these techniques.

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