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Takuji Fukumoto - One of the best experts on this subject based on the ideXlab platform.
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Hippocampal activation during associative encoding of word pairs and its relation to symptomatic improvement in depression: a functional and volumetric MRI study.
Journal of affective disorders, 2013Co-Authors: Shigeru Toki, Yasumasa Okamoto, Keiichi Onoda, Tomoya Matsumoto, Shinpei Yoshimura, Yoshihiko Kunisato, Go Okada, Kazuhiro Shishida, Makoto Kobayakawa, Takuji FukumotoAbstract:Altered emotional memory is one of the core cognitive functions that causes and maintains depression. Although many studies have investigated the relationship between hippocampal volume, depression and treatment response, no studies have investigated the relationship for hippocampal activity. Additionally, few studies have examined the relationship between functional and structural abnormalities in depression. We conducted a functional and volumetric MRI study investigating associative encoding of positive, negative and neutral word pairs in 13 healthy controls, and 14 untreated depressives. We carried out fMRI during a memory-encoding task at baseline. Treatment response was clinically assessed six weeks after pharmacotherapy began. Then, we explored the relation between brain activation during encoding of each word pair and symptomatic improvement. Relative to controls, depressives exhibited decreased activity in the Left Hippocampus during encoding positive word pairs and, in contrast, increased activity in the right Hippocampus during encoding negative or neutral word pairs. Poor response to treatment was associated with smaller activation within the Left Hippocampus during the memory encoding of positive word pairs. Overall results were not confounded by hippocampal volume. We could not appreciate any disease alteration during the retrieving phase. We found qualitative differences in Hippocampus functioning between depressives and healthy controls. In addition, the Left Hippocampus could have an effect on treatment response in depression by contributing to the dysfunctional encoding of positive information. © 2013 Elsevier B.V. All rights reserved.
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Hippocampal activation during associative encoding of word pairs and its relation to symptomatic improvement in depression: A functional and volumetric MRI study
Journal of Affective Disorders, 2013Co-Authors: Shigeru Toki, Yasumasa Okamoto, Keiichi Onoda, Tomoya Matsumoto, Shinpei Yoshimura, Yoshihiko Kunisato, Go Okada, Kazuhiro Shishida, Makoto Kobayakawa, Takuji FukumotoAbstract:Abstract Background Altered emotional memory is one of the core cognitive functions that causes and maintains depression. Although many studies have investigated the relationship between hippocampal volume, depression and treatment response, no studies have investigated the relationship for hippocampal activity. Additionally, few studies have examined the relationship between functional and structural abnormalities in depression. Methods We conducted a functional and volumetric MRI study investigating associative encoding of positive, negative and neutral word pairs in 13 healthy controls, and 14 untreated depressives. We carried out fMRI during a memory-encoding task at baseline. Treatment response was clinically assessed six weeks after pharmacotherapy began. Then, we explored the relation between brain activation during encoding of each word pair and symptomatic improvement. Results Relative to controls, depressives exhibited decreased activity in the Left Hippocampus during encoding positive word pairs and, in contrast, increased activity in the right Hippocampus during encoding negative or neutral word pairs. Poor response to treatment was associated with smaller activation within the Left Hippocampus during the memory encoding of positive word pairs. Overall results were not confounded by hippocampal volume. Limitations We could not appreciate any disease alteration during the retrieving phase. Conclusion We found qualitative differences in Hippocampus functioning between depressives and healthy controls. In addition, the Left Hippocampus could have an effect on treatment response in depression by contributing to the dysfunctional encoding of positive information.
Dominik Strzelecki - One of the best experts on this subject based on the ideXlab platform.
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Glycine transporter inhibitor sarcosine changes neuronal and glial parameters in the Left dorsolateral prefrontal cortex and glutamatergic parameters in the Left Hippocampus in stable schizophrenia
European Psychiatry, 2016Co-Authors: Dominik Strzelecki, M. Podgórski, O. Kałużyńska, Magdalena Kotlicka-antczak, O. Gawlik-kotelnicka, Agnieszka Gmitrowicz, L. Stefańczyk, P. GrzelakAbstract:Introduction Sarcosine - glycine transporter inhibitor - increases glycine concentration around NMDA (N-methyl-D-aspartate) receptors. Function of the glutamatergic system in the prefrontal cortex and Hippocampus is impaired in schizophrenia, which may lead to negative and cognitive symptomatology. Aims We evaluated the influence 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) and Left Hippocampus in patients with stable schizophrenia. Methods Fifty patients with schizophrenia, treated with constant antipsychotics doses, in stable clinical condition were randomly assigned (25 patients in each group) to administration of sarcosine (2 g) or placebo for six months. 1H-NMR spectroscopy (1.5 T) in both localisations and clinical evaluation (PANSS) was performed before and after sarcosine addition. Results Initially we noted no differences in metabolite concentrations between groups. In the Left DLPFC, NAA/Cho, mI/Cr and mI/Cho ratios were significantly higher in the sarcosine than the placebo group after six months. In the sarcosine group, NAA/Cr, NAA/Cho, mI/Cr, mI/Cho ratios also increased compared to baseline values. In the placebo group, only the NAA/Cr ratio increased. In the Left Hippocampus Glx/Cr and Glx/Cho decreased in sarcosine group at the end of our study. Conclusions The addition of sarcosine to antipsychotic therapy for six months caused increase of neurons viability (NAA) and neurogilal activity (mI) markers in the Left DLPFC and decrease of hyperglutamatergic overstimulation parameters in the Left Hippocampus with simultaneous improvement of clinical parameters including negative symptoms.
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Comparison of Metabolite Concentrations in the Left Dorsolateral Prefrontal Cortex, the Left Frontal White Matter, and the Left Hippocampus in Patients in Stable Schizophrenia Treated with Antipsychotics with or without Antidepressants. 1H-NMR Spectr
International journal of molecular sciences, 2015Co-Authors: Dominik Strzelecki, Magdalena Kotlicka-antczak, Michał Podgórski, Olga Kałużyńska, Ludomir Stefańczyk, Piotr Grzelak, Agnieszka GmitrowiczAbstract:Managing affective, negative, and cognitive symptoms remains the most difficult therapeutic problem in stable phase of schizophrenia. Efforts include administration of antidepressants. Drugs effects on brain metabolic parameters can be evaluated by means of proton nuclear magnetic resonance (1H-NMR) spectroscopy. We compared spectroscopic parameters in the Left prefrontal cortex (DLPFC), the Left frontal white matter (WM) and the Left Hippocampus and assessed the relationship between treatment and the spectroscopic parameters in both groups. We recruited 25 patients diagnosed with schizophrenia (DSM-IV-TR), with dominant negative symptoms and in stable clinical condition, who were treated with antipsychotic and antidepressive medication for minimum of three months. A group of 25 patients with schizophrenia, who were taking antipsychotic drugs but not antidepressants, was matched. We compared metabolic parameters (N-acetylaspartate (NAA), myo-inositol (mI), glutamatergic parameters (Glx), choline (Cho), and creatine (Cr)) between the two groups. All patients were also assessed with the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS). In patients receiving antidepressants we observed significantly higher NAA/Cr and NAA/Cho ratios within the DLPFC, as well as significantly higher mI/Cr within the frontal WM. Moreover, we noted significantly lower values of parameters associated with the glutamatergic transmission—Glx/Cr and Glx/Cho in the Hippocampus. Doses of antipsychotic drugs in the group treated with antidepressants were also significantly lower in the patients showing similar severity of psychopathology.
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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
Neuroscience Letters, 2015Co-Authors: Dominik Strzelecki, Agnieszka Gmitrowicz, Ludomir Stefańczyk, Michal Podgorski, Olga Kaluzynska, Oliwia Gawlikkotelnicka, Magdalena Kotlickaantczak, Piotr GrzelakAbstract: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.
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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
Neuroscience letters, 2015Co-Authors: Dominik Strzelecki, Magdalena Kotlicka-antczak, Agnieszka Gmitrowicz, Michał Podgórski, Olga Kałużyńska, Oliwia Gawlik-kotelnicka, Ludomir Stefańczyk, Piotr GrzelakAbstract: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.
Christoph Helmstaedter - One of the best experts on this subject based on the ideXlab platform.
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the overall pathological status of the Left Hippocampus determines preoperative verbal memory performance in Left mesial temporal lobe epilepsy
Hippocampus, 2014Co-Authors: Jurialexander Witt, Christian E. Elger, Roland Coras, Johannes Schramm, Albert J Becker, Ingmar Blumcke, Christoph HelmstaedterAbstract:Studies on hippocampal cell loss in epilepsy have produced diverging evidence as to which subfields are specifically related to memory. This may be due to rather small and often heterogeneous samples, or to different memory measures. Therefore, the current study examined hippocampal cell densities and memory in a large sample of patients with solely mesial temporal lobe epilepsy (mTLE), employing measures with proven sensitivity to mesiotemporal pathology. In 104 patients who had undergone epilepsy surgery for mTLE, we evaluated the role of segmental hippocampal cell loss and its underlying factor structure with regard to presurgical verbal and figural memory while controlling for side-of-surgery and hemispheric dominance. First of all, patients showed material-specific memory impairment concordant with the lateralization of epilepsy. Factor analysis of segmental cell loss revealed a single factor reflecting the overall integrity of the Hippocampus. The overall pathological status of the Left Hippocampus correlated with verbal memory parameters (r = 0.33–0.34, P < 0.05), especially when controlling for atypical hemispheric dominance (r = 0.50–0.57, P < 0.01), and explained up to 33% of the observed variance. Further analyses revealed no superior role of a single subfield or cell loss pattern for memory performance. No systematic relations between neuronal cell densities of the right Hippocampus and memory function were found, nor did Left or right hippocampal pathology explain figural memory parameters. The results suggest that the overall pathological status of the Left Hippocampus – rather than a specific subfield pathology – is predictive for verbal memory in mTLE. The finding that figural memory parameters, although sensitive to right mTLE, were not related to neuronal cell densities of the right Hippocampus, puts the Left/right Hippocampus verbal/nonverbal memory dichotomy into perspective. © 2014 Wiley Periodicals, Inc.
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The overall pathological status of the Left Hippocampus determines preoperative verbal memory performance in Left mesial temporal lobe epilepsy.
Hippocampus, 2013Co-Authors: Jurialexander Witt, Christian E. Elger, Roland Coras, Johannes Schramm, Albert J Becker, Ingmar Blumcke, Christoph HelmstaedterAbstract:Studies on hippocampal cell loss in epilepsy have produced diverging evidence as to which subfields are specifically related to memory. This may be due to rather small and often heterogeneous samples, or to different memory measures. Therefore, the current study examined hippocampal cell densities and memory in a large sample of patients with solely mesial temporal lobe epilepsy (mTLE), employing measures with proven sensitivity to mesiotemporal pathology. In 104 patients who had undergone epilepsy surgery for mTLE, we evaluated the role of segmental hippocampal cell loss and its underlying factor structure with regard to presurgical verbal and figural memory while controlling for side-of-surgery and hemispheric dominance. First of all, patients showed material-specific memory impairment concordant with the lateralization of epilepsy. Factor analysis of segmental cell loss revealed a single factor reflecting the overall integrity of the Hippocampus. The overall pathological status of the Left Hippocampus correlated with verbal memory parameters (r = 0.33–0.34, P
Agnieszka Gmitrowicz - One of the best experts on this subject based on the ideXlab platform.
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Glycine transporter inhibitor sarcosine changes neuronal and glial parameters in the Left dorsolateral prefrontal cortex and glutamatergic parameters in the Left Hippocampus in stable schizophrenia
European Psychiatry, 2016Co-Authors: Dominik Strzelecki, M. Podgórski, O. Kałużyńska, Magdalena Kotlicka-antczak, O. Gawlik-kotelnicka, Agnieszka Gmitrowicz, L. Stefańczyk, P. GrzelakAbstract:Introduction Sarcosine - glycine transporter inhibitor - increases glycine concentration around NMDA (N-methyl-D-aspartate) receptors. Function of the glutamatergic system in the prefrontal cortex and Hippocampus is impaired in schizophrenia, which may lead to negative and cognitive symptomatology. Aims We evaluated the influence 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) and Left Hippocampus in patients with stable schizophrenia. Methods Fifty patients with schizophrenia, treated with constant antipsychotics doses, in stable clinical condition were randomly assigned (25 patients in each group) to administration of sarcosine (2 g) or placebo for six months. 1H-NMR spectroscopy (1.5 T) in both localisations and clinical evaluation (PANSS) was performed before and after sarcosine addition. Results Initially we noted no differences in metabolite concentrations between groups. In the Left DLPFC, NAA/Cho, mI/Cr and mI/Cho ratios were significantly higher in the sarcosine than the placebo group after six months. In the sarcosine group, NAA/Cr, NAA/Cho, mI/Cr, mI/Cho ratios also increased compared to baseline values. In the placebo group, only the NAA/Cr ratio increased. In the Left Hippocampus Glx/Cr and Glx/Cho decreased in sarcosine group at the end of our study. Conclusions The addition of sarcosine to antipsychotic therapy for six months caused increase of neurons viability (NAA) and neurogilal activity (mI) markers in the Left DLPFC and decrease of hyperglutamatergic overstimulation parameters in the Left Hippocampus with simultaneous improvement of clinical parameters including negative symptoms.
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Comparison of Metabolite Concentrations in the Left Dorsolateral Prefrontal Cortex, the Left Frontal White Matter, and the Left Hippocampus in Patients in Stable Schizophrenia Treated with Antipsychotics with or without Antidepressants. 1H-NMR Spectr
International journal of molecular sciences, 2015Co-Authors: Dominik Strzelecki, Magdalena Kotlicka-antczak, Michał Podgórski, Olga Kałużyńska, Ludomir Stefańczyk, Piotr Grzelak, Agnieszka GmitrowiczAbstract:Managing affective, negative, and cognitive symptoms remains the most difficult therapeutic problem in stable phase of schizophrenia. Efforts include administration of antidepressants. Drugs effects on brain metabolic parameters can be evaluated by means of proton nuclear magnetic resonance (1H-NMR) spectroscopy. We compared spectroscopic parameters in the Left prefrontal cortex (DLPFC), the Left frontal white matter (WM) and the Left Hippocampus and assessed the relationship between treatment and the spectroscopic parameters in both groups. We recruited 25 patients diagnosed with schizophrenia (DSM-IV-TR), with dominant negative symptoms and in stable clinical condition, who were treated with antipsychotic and antidepressive medication for minimum of three months. A group of 25 patients with schizophrenia, who were taking antipsychotic drugs but not antidepressants, was matched. We compared metabolic parameters (N-acetylaspartate (NAA), myo-inositol (mI), glutamatergic parameters (Glx), choline (Cho), and creatine (Cr)) between the two groups. All patients were also assessed with the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS). In patients receiving antidepressants we observed significantly higher NAA/Cr and NAA/Cho ratios within the DLPFC, as well as significantly higher mI/Cr within the frontal WM. Moreover, we noted significantly lower values of parameters associated with the glutamatergic transmission—Glx/Cr and Glx/Cho in the Hippocampus. Doses of antipsychotic drugs in the group treated with antidepressants were also significantly lower in the patients showing similar severity of psychopathology.
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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
Neuroscience Letters, 2015Co-Authors: Dominik Strzelecki, Agnieszka Gmitrowicz, Ludomir Stefańczyk, Michal Podgorski, Olga Kaluzynska, Oliwia Gawlikkotelnicka, Magdalena Kotlickaantczak, Piotr GrzelakAbstract: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.
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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
Neuroscience letters, 2015Co-Authors: Dominik Strzelecki, Magdalena Kotlicka-antczak, Agnieszka Gmitrowicz, Michał Podgórski, Olga Kałużyńska, Oliwia Gawlik-kotelnicka, Ludomir Stefańczyk, Piotr GrzelakAbstract: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.
Piotr Grzelak - One of the best experts on this subject based on the ideXlab platform.
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Comparison of Metabolite Concentrations in the Left Dorsolateral Prefrontal Cortex, the Left Frontal White Matter, and the Left Hippocampus in Patients in Stable Schizophrenia Treated with Antipsychotics with or without Antidepressants. 1H-NMR Spectr
International journal of molecular sciences, 2015Co-Authors: Dominik Strzelecki, Magdalena Kotlicka-antczak, Michał Podgórski, Olga Kałużyńska, Ludomir Stefańczyk, Piotr Grzelak, Agnieszka GmitrowiczAbstract:Managing affective, negative, and cognitive symptoms remains the most difficult therapeutic problem in stable phase of schizophrenia. Efforts include administration of antidepressants. Drugs effects on brain metabolic parameters can be evaluated by means of proton nuclear magnetic resonance (1H-NMR) spectroscopy. We compared spectroscopic parameters in the Left prefrontal cortex (DLPFC), the Left frontal white matter (WM) and the Left Hippocampus and assessed the relationship between treatment and the spectroscopic parameters in both groups. We recruited 25 patients diagnosed with schizophrenia (DSM-IV-TR), with dominant negative symptoms and in stable clinical condition, who were treated with antipsychotic and antidepressive medication for minimum of three months. A group of 25 patients with schizophrenia, who were taking antipsychotic drugs but not antidepressants, was matched. We compared metabolic parameters (N-acetylaspartate (NAA), myo-inositol (mI), glutamatergic parameters (Glx), choline (Cho), and creatine (Cr)) between the two groups. All patients were also assessed with the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale for Schizophrenia (CDSS). In patients receiving antidepressants we observed significantly higher NAA/Cr and NAA/Cho ratios within the DLPFC, as well as significantly higher mI/Cr within the frontal WM. Moreover, we noted significantly lower values of parameters associated with the glutamatergic transmission—Glx/Cr and Glx/Cho in the Hippocampus. Doses of antipsychotic drugs in the group treated with antidepressants were also significantly lower in the patients showing similar severity of psychopathology.
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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
Neuroscience Letters, 2015Co-Authors: Dominik Strzelecki, Agnieszka Gmitrowicz, Ludomir Stefańczyk, Michal Podgorski, Olga Kaluzynska, Oliwia Gawlikkotelnicka, Magdalena Kotlickaantczak, Piotr GrzelakAbstract: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.
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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
Neuroscience letters, 2015Co-Authors: Dominik Strzelecki, Magdalena Kotlicka-antczak, Agnieszka Gmitrowicz, Michał Podgórski, Olga Kałużyńska, Oliwia Gawlik-kotelnicka, Ludomir Stefańczyk, Piotr GrzelakAbstract: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.