Serum levels of S100B in patients with chronic schizophrenia during treatment augmentation with sarcosine: results of the double-blind, randomized, placebo-controlled PULSAR study.

Introduction: Sarcosine (N-methylglycine) normalizes glutamatergic neurotransmission in schizophrenia and ameliorates primary negative symptoms. This amino acid may also directly or indirectly influence glial function and therefore levels of S100B, calcium-binding protein linked with glial pathology. Aim: Investigating an association between initial S100B serum concentrations as a glial marker, its changes, and symptoms severity during use of sarcosine in patients with predominant negative symptoms and stable antipsychotic treatment. Methods: Sixty subjects with a diagnosis of schizophrenia with predominant negative symptoms completed a 6-month randomized, double-blinded, placebo-controlled prospective study. Participants were randomly assigned in 1:1 ratio and received 2 g of sarcosine or placebo daily Results: At baseline, no differences were observed between the sarcosine and placebo groups in PANSS or CDSS scores (all p > 0.35). Sarcosine augmentation led to significantly greater improvement in total, negative, and general psychopathology PANSS scores compared with placebo (t = 2.88-8.23, all p ≤ 0.006), while improvement in depressive symptoms did not reach significance (p = 0.10). Serum S100B levels did not differ between groups at any time point (all p ≥ 0.14; d = -0.06 to -0.40). Mixed-effects ANOVA showed a significant effect of visit on S100B (F (2,52) = 6.10, p = 0.005, η Conclusion: Sarcosine does not significantly affect S100B concentrations. S100B may be involved in mechanisms related to the presence of affective symptoms in schizophrenia. Clinical Trial Registration: Clinicaltrials.gov, identifier NCT01503359.