Introduction: The criteria for “at-risk mental state" have been advocated as a preventive approach to psychosis treatment although their pathophysiological mechanisms remain unclear. Reliable biomarkers to predict transitions from at-risk mental state to psychosis are urgently needed. Since abnormalities in N-methyl-D-aspartate receptor co-agonists have been reported in the serum of patients with schizophrenia, several of these metabolite levels in individuals with at-risk mental state were investigated and these levels with clinical symptoms were correlated. Methods: Serum levels of glutamate, cysteine, glycine, γ-glutamylcysteine, glutathione, D-serine, and L-serine were investigated in antipsychotic-naïve individuals with attenuated psychotic symptoms (n = 28) and compared with those in antipsychotic-naïve individuals with first-episode psychosis (n = 13) and those in healthy controls (n = 41). The serum metabolite levels were measured using high-performance liquid chromatography with fluorescence detection or liquid chromatography with tandem mass spectrometry. Correlations between clinical symptoms and serum metabolite levels in individuals with at-risk mental state were also examined. Results: The glutathione and D-serine levels were significantly lower, whereas glutamate levels were significantly higher in individuals with attenuated psychotic symptoms than in healthy controls. Additionally, glutathione levels were significantly decreased in individuals with first-episode psychosis compared with those in healthy controls. In individuals with attenuated psychotic symptoms, clinical scores were not correlated with serum levels of metabolites related to the N-methyl-D-aspartate receptor. Conclusions: The results of this study suggest that abnormally altered levels of metabolites related to the N-methyl-D-aspartate receptor can already occur in individuals with attenuated psychotic symptoms.
Tagata et al. (Mon,) studied this question.