Abstract
The glutamatergic system is a key point in pathogenesis of schizophrenia. Sarcosine (N-methylglycine) is an exogenous amino acid that acts as a glycine transporter inhibitor. It modulates glutamatergic transmission by increasing glycine concentration around NMDA (N-methyl-d-aspartate) receptors. In patients with schizophrenia, the function of the glutamatergic system in the prefrontal cortex is impaired, which may promote negative and cognitive symptoms. Proton nuclear magnetic resonance (1H-NMR) spectroscopy is a non-invasive imaging method enabling the evaluation of brain metabolite concentration, which can be applied to assess pharmacologically induced changes. The aim of the study was to evaluate the influence of a six-month course of sarcosine therapy on the concentration of metabolites (NAA, N-acetylaspartate; Glx, complex of glutamate, glutamine and γ-aminobutyric acid (GABA); mI, myo-inositol; Cr, creatine; Cho, choline) in the left dorso-lateral prefrontal cortex (DLPFC) in patients with stable schizophrenia. Fifty patients with schizophrenia, treated with constant antipsychotics doses, in stable clinical condition were randomly assigned to administration of sarcosine (25 patients) or placebo (25 patients) for six months. Metabolite concentrations in DLPFC were assessed with 1.5 Tesla 1H-NMR spectroscopy. Clinical symptoms were evaluated with the Positive and Negative Syndrome Scale (PANSS). The first spectroscopy revealed no differences in metabolite concentrations between groups. After six months, NAA/Cho, mI/Cr and mI/Cho ratios in the left DLPFC were significantly higher in the sarcosine than the placebo group. In the sarcosine group, NAA/Cr, NAA/Cho, mI/Cr, mI/Cho ratios also significantly increased compared to baseline values. In the placebo group, only the NAA/Cr ratio increased. The addition of sarcosine to antipsychotic therapy for six months increased markers of neurons viability (NAA) and neurogilal activity (mI) with simultaneous improvement of clinical symptoms. Sarcosine, two grams administered daily, seems to be an effective adjuvant in the pharmacotherapy of schizophrenia.
Highlights
IntroductionSchizophrenia is one of the most devastating mental diseases, with lifetime prevalence from
Schizophrenia is one of the most devastating mental diseases, with lifetime prevalence from0.30% to 0.66% and incidence between 10.2 and 22.0 per 100,000 person-years [1]
The aim of the study is to evaluate the influence of sarcosine therapy on the concentrations of NAA, Glx, mI, Cho and Cr in the dorso-lateral prefrontal cortex (DLPFC) of the left frontal lobe in patients with schizophrenia
Summary
Schizophrenia is one of the most devastating mental diseases, with lifetime prevalence from. Meta-analyses performed by Steen and Brugger [21,22] found that the NAA concentration in the PFC was similar in patients with a first episode of schizophrenia and in the chronic phase of the disease. Antipsychotics increased levels of NAA after treatment [34,41], while in others, there were no significant changes [28,42,43,44] It remains unclear if substances modifying glutamatergic transmission cause changes in concentrations of CNS metabolites detectable in spectroscopy. The aim of the study is to evaluate the influence of sarcosine therapy on the concentrations of NAA, Glx (complex of glutamate, glutamine and γ-aminobutyric acid GABA), mI (myo-inositol), Cho (choline-containing compounds) and Cr (creatine plus phosphocreatine) in the DLPFC of the left frontal lobe in patients with schizophrenia. It can reveal new aspects of the role played by the glutamatergic system in the pathogenesis of schizophrenia
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