From the neurochemical perspective, negative and cognitive symptoms are associated with impairment of the glutamatergic system, especially in the PFC, where ionotropic NMDA receptors are abundant [10,11,12]. Glycine is a necessary co-agonist of the NMDA receptor, and sarcosine (N-methylglycine) is an exogenous amino acid that acts as an inhibitor of glycine transporter type 1 (GlyT-1) [13]. Thus, sarcosine should improve the inadequate function of NMDA receptors [12]: a hypothesis confirmed by the observed reduction of schizophrenia symptoms (negative and total symptomatology) associated with the augmentation of antipsychotic therapy with sarcosine [14,15,16,17,18] excluding clozapine [19] or treatment with sarcosine alone [20].
