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 per os . S100B serum concentrations and severity of symptoms assessments were done in parallel at the beginning, after 6 weeks, and after 6 months of the study. Finally, we obtained results from 15 participants in the sarcosine group and 12 in the placebo group after 6 weeks of receiving augmentation, and from 26 patients in the sarcosine group and 28 in the control group after 6 months of the study. For the clinical evaluation, we used the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS). 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 2 = 0.12), with no group or interaction effects. Exploratory analyses suggested heterogeneous S100B trajectories across affective outcome subgroups (H = 8.54–9.20, p = 0.03–0.04); however, adjusted regression models did not confirm independent associations with changes in PANSS or CDSS scores. 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.