Serum levels of TNF-alpha in patients with chronic schizophrenia during treatment augmentation with sarcosine (results of the PULSAR study)

Sarcosine, glycine transporter inhibitor, increases glycine levels around NMDA receptor, improving primary negative symptoms of schizophrenia. The aim of our study was to find a potential relationship between initial TNF-alpha level, its changes and schizophrenia symptoms severity, resulting from adding sarcosine to a stable antipsychotic treatment. Sixty subjects with stable schizophrenia were randomized to receive either 2 g of sarcosine or placebo and completed a 6-month, double blind, placebo-controlled study. Three patients on sarcosine and one taking placebo did not complete TNF-alpha tests, planned at the beginning, after 6 weeks and after 6 months. For clinical assessments we used PANSS and CDSS scales. No changes in TNF-alpha serum concentrations in both groups at any time-points was noted. The sarcosine group achieved significant improvement in negative symptoms, general psychopathology and total PANSS score group, however without any significant correlations between TNF-alpha levels and PANSS scores in all assessments. Positive correlations between TNF-alpha levels and CDSS score were found in the placebo group and total study group. Initial TNF-alpha concentrations cannot be used as a predictor of the improvement resulting from adding sarcosine. Sarcosine does not significantly affect TNF-alpha levels. TNF-alpha may be involved in mechanisms related to depressive symptomatology in schizophrenia.