We previously reported that plasma levels of glycine, a co-agonist at N-methyl-D-asparate (NMDA)-type glutamate receptors, are decreased in patients with schizophrenia, and that glycine levels are negatively correlated with negative symptoms. The aim of the present study was to determine if glycine, or its ratio to serine, a precursor of glycine, predicts change in negative symptoms in subjects with schizophrenia during treatment with clozapine, an atypical antipsychotic drug with multiple effects on glutamatergic activity. Plasma levels of glycine, serine, and their ratio, were measured in 44 patients with schizophrenia who were subsequently treated with clozapine. Baseline glycine levels or glycine/serine ratios predicted the Scale for the Assessment of Negative Symptoms - Sum of the Global Scales and Avolition-Apathy after 6 wk of clozapine treatment. These results indicate the association of these amino acid measures with response to clozapine in terms of negative symptoms in patients with schizophrenia.
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