Attached is the full paper for this research and some highlights summarized below:
Supplementation of antipsychotic treatment with sarcosine – G1yT1 inhibitor – causes changes of glutamatergic 1NMR spectroscopy parameters in the left hippocampus in patients with stable schizophrenia
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.
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), whille Nacetylaspartate (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 antipsychotic 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.
Lately, it was proposed that glutamatergic and GABAergic systems may be involved in the pathogenesis of schizophrenia. NMDA (N-methyl-d-aspartate) receptors are located all over the brain, but location on inhibitory GABAergic neurons is especially an object of interest. Lack of adequate control on glutamatergic transmission
(also influencing dopaminergic system) causes information bias and both negative and cognitive symptoms in schizophrenia [3–5]. Sarcosine – an exogenous amino acid – is serving in the brain as a glycine transporter type 1 (GlyT-1) inhibitor and as a source of glycine (natural coagonist of the NMDA receptor, metabolized from sarcosine by sarcosine dehydrogenase) . It was reported to be effective in treating negative and cognitive symptoms .
Supplementation of sarcosine at a 2 grams daily dose is supposed to increase glycine concentration and normalize hypofunction of the NMDA receptors, which are present in high density in the the prefrontal cortex and hippocampus—areas associated with development of cognitive and negative symptomatology
At baseline examination there were no differences regarding spectroscopic parameters between both studied groups (Table 2). There were also no significant differences in substance concentration ratios between sarcosine and placebo group on second assessment. However, after the therapy in the experimental group,
Glx/Cr and Glx/Cho ratios significantly decreased comparing to baseline values (21,4% and 21,2%, respectively).
At the beginning of the experiment, there was no significant difference in the PANSS scores between both groups However at the end of the experiment patients treated with sarcosine had significantly lower results in negative and general psychopathology subscales and total score in the PANSS
To our knowledge, this is the first study assessing the effects of sarcosine (or glutamatergic agents) on spectroscopic parameters in the hippocampus of patients with schizophrenia. Differences in Glx/Cr and Glx/Cho ratios in the experimental group indicate that 2 g of sarcosine daily is a sufficient dose to cross the blood–brain barrier and affect the glutamatergic function within hippocampus as well as improve mental status of patients with schizophrenia.
Limitations of the study
Due to the small number of patients and the technical limitations of spectroscopy performed with 1.5T magnetic field, conclusions should be drawn carefully.
We conclude that augmentation of the antypsychotic treatment with sarcosine may reverse the increase in glutamatergic transmission in the left hippocampus in schizophrenia along with improvement of mental state, assessed with the PANSS. 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.
Conflict of interest
No potential conflict of interest
Full Paper Below:
SarcosineSchizophreniaGlutamate.pdf (797.4 KB)