Supplementation of antipsychotic treatment with sarcosine – GlyT1 inhibitor – causes changes of glutamatergic 1NMR spectroscopy parameters in the left hippocampus in patients with stable schizophrenia

Strzelecki, Dominik; Podgórski, Michał; Kałużyńska, Olga; Gawlik-Kotelnicka, Oliwia; Stefańczyk, Ludomir; Kotlicka-Antczak, Magdalena; Gmitrowicz, Agnieszka; Grzelak, Piotr

doi:10.1016/j.neulet.2015.08.039

Cited by 30 publications

(24 citation statements)

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“… 38 A recent study examined how the administration of sarcosine, a GlyT1 inhibitor, affected metabolite concentrations in the hippocampus and found that Glx/Cr and Glx/Cho were decreased after treatment. 42 A potential future study could use high-field 1 H-MRS to detect Gly, Gln and Glu concentrations in the thalamus before and after a Gly- or Glu-modulating medication.…”

Section: Discussionmentioning

confidence: 99%

Neurometabolic abnormalities in schizophrenia and depression observed with magnetic resonance spectroscopy at 7 T

et al. 2017

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BackgroundExamining neurometabolic abnormalities in critical brain areas in schizophrenia and major depressive disorder (MDD) may help guide future pharmacological interventions including glutamate-modulating treatments.AimsTo measure metabolite concentrations within the anterior cingulate cortex (ACC) and thalamus of people with schizophrenia and people with MDD.MethodsSpectra were acquired from 16 volunteers with schizophrenia, 17 with MDD and 18 healthy controls using magnetic resonance spectroscopy on a 7 Tesla scanner.ResultsIn the thalamus, there were lower glycine concentrations in the schizophrenia group relative to control (P=0.017) and MDD groups (P=0.012), and higher glutamine concentrations relative to healthy controls (P=0.009). In the thalamus and the ACC, the MDD group had lower myo-inositol concentrations than the control (P=0.014, P=0.009, respectively) and schizophrenia (P=0.004, P=0.002, respectively) groups.ConclusionThese results support the glutamatergic theory of schizophrenia and indicate a potential glycine deficiency in the thalamus. In addition, reduced myo-inositol concentrations in MDD suggest its involvement in the disorder.Declaration of interestNone.Copyright and usage© The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

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Section: Discussionmentioning

confidence: 99%

Neurometabolic abnormalities in schizophrenia and depression observed with magnetic resonance spectroscopy at 7 T

et al. 2017

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“…Inhibition of GlyT1 leads to an increase in cerebral glycine concentration and improvements in negative symptoms and cognitive deficits of patients with schizophrenia (see (Javitt, ) for review). The beneficial effects of treatment with sarcosine, a GlyT1 inhibitor, on the symptoms of schizophrenic patients were also concluded from a recently published phase III study (Strzelecki et al, ).…”

Section: Introductionmentioning

confidence: 90%

Comparative evaluation of two glycine transporter 1 radiotracers [¹¹C]GSK931145 and [¹⁸F]MK-6577 in baboons

Zheng

Lin

Holden

et al. 2016

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Glycine transporter type-1 (GlyT1) has been proposed as a target for drug development for schizophrenia. PET imaging with a GlyT1 specific radiotracer will allow for the measurement of target occupancy of GlyT1 inhibitors, and for in vivo investigation of GlyT1 alterations in schizophrenia. We conducted a comparative evaluation of two GlyT1 radiotracers, [(11) C]GSK931145, and [(18) F]MK-6577, in baboons. Two baboons were imaged with [(11) C]GSK931145 and [(18) F]MK-6577. Blocking studies with GSK931145 (0.3 or 0.2 mg/kg) were conducted to determine the level of tracer specific binding. [(11) C]GSK931145 and [(18) F]MK-6577 were synthesized in good yield and high specific activity. Moderately fast metabolism was observed for both tracers, with ∼ 30% of parent at 30 min post-injection. In the brain, both radiotracers showed good uptake and distribution profiles consistent with regional GlyT1 densities. [(18) F]MK-6577 displayed higher uptake and faster kinetics than [(11) C]GSK931145. Time activity curves were well described by the two-tissue compartment model. Regional volume of distribution (VT ) values were higher for [(18) F]MK-6577 than [(11) C]GSK931145. Pretreatment with GSK931145 reduced tracer uptake to a homogeneous level throughout the brain, indicating in vivo binding specificity and lack of a reference region for both radiotracers. Linear regression analysis of VT estimates between tracers indicated higher specific binding for [(18) F]MK-6577 than [(11) C]GSK931145, consistent with higher regional binding potential (BPND ) values of [(18) F]MK-6577 calculated using VT from the baseline scans and non-displaceable distribution volume (VND ) derived from blocking studies. [(18) F]MK-6577 appears to be a superior radiotracer with higher brain uptake, faster kinetics, and higher specific binding signals than [(11) C]GSK931145.

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“…Sarcosine (N-methylglycine) is a potent endogenous non-selective GlyT1 inhibitor. In our search of the literature, we identified seven clinical trials [41,43,[67][68][69][70][71], one open label trial [72] and two case reports [73,74] on use of sarcosine in patients with schizophrenia including a total of 141 completers in the active arm. All trials used sarcosine at the dose of 2 g/d, except the Amiaz et al (2015) [72] open trial which used 4 g/d.…”

Section: Sarcosinementioning

confidence: 99%

“…Six trials reported improvement in a range of clinical outcomes including positive, negative, depressive and cognitive symptoms, general psychopathology and total PANSS scores [41,43,67,[69][70][71]. Lane et al (2005) [41] and (2010) [43] reported improvement in outcome measures with adjunct sarcosine (2gr/day for 6 weeks) but not D-serine (see D-serine section for details).…”

Section: Sarcosinementioning

confidence: 99%

“…Their result indicated add-on sarcosine was associated with statistically significant improvement in PANSS negative and general psychopathology scores in comparison to placebo. Furthermore, using Proton nuclear magnetic resonance (H-NMR) spectroscopy, they demonstrated reversal of the pathological increase in glutamatergic transmission in the left frontal lobe [75] and hippocampus [70] as well as increased markers of neuron viability and neuroglial activity in the left dorsolateral prefrontal cortex (DLPFC) [76].…”

Section: Sarcosinementioning

confidence: 99%

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Glutamate modulators for treatment of schizophrenia

Zhand

Attwood

Harvey

2019

Personalized Medicine in Psychiatry

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Supplementation of antipsychotic treatment with sarcosine – GlyT1 inhibitor – causes changes of glutamatergic 1NMR spectroscopy parameters in the left hippocampus in patients with stable schizophrenia

Cited by 30 publications

References 58 publications

Neurometabolic abnormalities in schizophrenia and depression observed with magnetic resonance spectroscopy at 7 T

Neurometabolic abnormalities in schizophrenia and depression observed with magnetic resonance spectroscopy at 7 T

Comparative evaluation of two glycine transporter 1 radiotracers [¹¹C]GSK931145 and [¹⁸F]MK-6577 in baboons

Glutamate modulators for treatment of schizophrenia

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Supplementation of antipsychotic treatment with sarcosine – GlyT1 inhibitor – causes changes of glutamatergic 1NMR spectroscopy parameters in the left hippocampus in patients with stable schizophrenia

Cited by 30 publications

References 58 publications

Neurometabolic abnormalities in schizophrenia and depression observed with magnetic resonance spectroscopy at 7 T

Neurometabolic abnormalities in schizophrenia and depression observed with magnetic resonance spectroscopy at 7 T

Comparative evaluation of two glycine transporter 1 radiotracers [11C]GSK931145 and [18F]MK-6577 in baboons

Glutamate modulators for treatment of schizophrenia

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Comparative evaluation of two glycine transporter 1 radiotracers [¹¹C]GSK931145 and [¹⁸F]MK-6577 in baboons