Supplementation of Antipsychotic Treatment with the Amino Acid Sarcosine Influences Proton Magnetic Resonance Spectroscopy Parameters in Left Frontal White Matter in Patients with Schizophrenia

Nutrients

Dominik Strzelecki³  Michał Podgórski¹  Olga Kałużyńska³  Oliwia Gawlik-Kotelnicka³  Ludomir Stefaᑌzyk¹  Magdalena Kotlicka-Antczak³  Agnieszka Gmitrowicz² 

[1] Department of Radiology—Diagnostic Imaging, Medical University of Łódź, Łódź 92-213, Poland;Department of Adolescent Psychiatry, Medical University of Łódź, Łódź 92-213, Poland;Department of Affective and Psychotic Disorders, Medical University of Łódź, Central Clinical Hospital, ul. Pomorska 251, Łódź 92-213, Poland;

关键词: sarcosine;    glutamate;    white matter;    frontal lobe;    ¹H-NMR spectroscopy;    schizophrenia;   

DOI  :  10.3390/nu7105427

来源: mdpi

【 摘 要 】

Dysfunction of the glutamatergic system, the main stimulating system in the brain, has a major role in pathogenesis of schizophrenia. The frontal white matter (WM) is partially composed of axons from glutamatergic pyramidal neurons and glia with glutamatergic receptors. The natural amino acid sarcosine, a component of a normal diet, inhibits the glycine type 1 transporter, increasing the glycine level. Thus, it modulates glutamatergic transmission through the glutamatergic ionotropic NMDA (N-methyl-d-aspartate) receptor, which requires glycine as a co-agonist. To evaluate the concentrations of brain metabolites (NAA, N-acetylaspartate; Glx, complex of glutamate, glutamine, and γ-aminobutyric acid (GABA); mI, myo-inositol; Cr, creatine; Cho, choline) in the left frontal WM, Proton Nuclear Magnetic Resonance (¹H-NMR) spectroscopy was used. Twenty-five patients randomly chosen from a group of fifty with stable schizophrenia (DSM-IV-TR) and dominant negative symptoms, who were receiving antipsychotic therapy, were administered 2 g of sarcosine daily for six months. The remaining 25 patients received placebo. Assignment was double blinded. ¹H-NMR spectroscopy (1.5 T) was performed twice: before and after the intervention. NAA, Glx and mI were evaluated as Cr and Cho ratios. All patients were also assessed twice with the Positive and Negative Syndrome Scale (PANSS). Results were compared between groups and in two time points in each group. The sarcosine group demonstrated a significant decrease in WM Glx/Cr and Glx/Cho ratios compared to controls after six months of therapy. In the experimental group, the final NAA/Cr ratio significantly increased and Glx/Cr ratio significantly decreased compared to baseline values. Improvement in the PANSS scores was significant only in the sarcosine group. In patients with schizophrenia, sarcosine augmentation can reverse the negative effect of glutamatergic system overstimulation, with a simultaneous beneficial increase of NAA/Cr ratio in the WM of the left frontal lobe. Our results further support the glutamatergic hypothesis of schizophrenia.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.