Adding Sarcosine to Antipsychotic Treatment in Patients with Stable Schizophrenia Changes the Concentrations of Neuronal and Glial Metabolites in the Left Dorsolateral Prefrontal Cortex.
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.
Department of Affective and Psychotic Disorders, Medical University of Łódź, Central Clinical Hospital, Łódź 92-213, Poland. dominik.strzelecki@umed.lodz.pl.
Dominik
D
Strzelecki
Department of Radiology-Diagnostic Imaging, Medical University of Łódź, Barlicki University Hospital No. 1, Łódź 90-153, Poland. chilam@tlen.pl.
Michał
M
Podgórski
Department of Affective and Psychotic Disorders, Medical University of Łódź, Central Clinical Hospital, Łódź 92-213, Poland. okaluzynska@gmail.com.
Olga
O
Kałużyńska
Department of Radiology-Diagnostic Imaging, Medical University of Łódź, Barlicki University Hospital No. 1, Łódź 90-153, Poland. ludomir.stefanczyk@umed.lodz.pl.
Ludomir
L
Stefańczyk
Department of Affective and Psychotic Disorders, Medical University of Łódź, Central Clinical Hospital, Łódź 92-213, Poland. magdalena.kotlicka-antczak@umed.lodz.pl.
Magdalena
M
Kotlicka-Antczak
Department of Adolescent Psychiatry, Medical University of Łódź, Central Clinical Hospital, Łódź 92-213, Poland. agnieszka.gmitrowicz@umed.lodz.pl.
Agnieszka
A
Gmitrowicz
Department of Radiology-Diagnostic Imaging, Medical University of Łódź, Barlicki University Hospital No. 1, Łódź 90-153, Poland. piotr.grzelak@umed.lodz.pl.
Piotr
P
Grzelak
D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D066244:Proton Magnetic Resonance Spectroscopy; D012521:Sarcosine / Q000494:pharmacology / Q000627:therapeutic use*; D012559:Schizophrenia / Q000188:drug therapy*
D014150:Antipsychotic Agents; D012521:Sarcosine
1H-NMR spectroscopy; NMDA receptor; dorso-lateral prefrontal cortex; glutamate; sarcosine; schizophrenia