Glutamatergic system, the main stimulating system of the brain, plays an important role in the pathogenesis of
schizophrenia. Hippocampus, a structure crucial for memory and cognitive functions and rich in glutamatergic neurons, is a natural object of interest in studies on
psychoses.
Sarcosine, a
glycine transporter (GlyT-1) inhibitor influences the function of
NMDA receptor and
glutamate-dependent transmission. The aim of the study was to assess the effects of
sarcosine on metabolism parameters in the left hippocampus in patients with
schizophrenia. Assessments were performed using
proton nuclear magnetic resonance ((1)H NMR) spectroscopy (1.5T). Fifty patients diagnosed with
schizophrenia (DSM-IV-TR), with dominant negative symptoms, in stable clinical condition and stable
antipsychotics doses were treated either with
sarcosine (n=25) or placebo (n=25). Spectroscopic parameters were evaluated within groups and between two groups before and after 6-month intervention. All patients were also assessed with the Positive and Negative Syndrome Scale (PANSS). In the
sarcosine group, after 6-month treatment, we found significant decrease in hippocampal Glx/Cr (Glx-complex of
glutamate,
glutamine and
GABA, Cr-
creatine) and Glx/Cho (Cho-
choline), while
N-acetylaspartate (NAA), myo-
inositol (mI), Cr and Cho parameters remained stable along the study and also did not differ significantly between both groups. This is the first study showing that a pharmacological intervention in
schizophrenia, particularly augmentation of the antypsychotic treatment with
sarcosine, may reverse the pathological increase in glutamatergic transmission in the hippocampus. The results confirm involvement of glutamatergic system in the pathogenesis of
schizophrenia and demonstrate beneficial effects of GlyT-1 inhibitor on the metabolism in the hippocampus and symptoms of
schizophrenia.