***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: OBJECTIVE Augmentation of sarcosine , a natural inhibitor of the glycine transporter type I , normalizes glutamatergic neurotransmission , having beneficial impact on primary negative symptoms in schizophrenia and may also influence immune system and interleukin 6 ( IL-6 ) levels . AIM Finding a relationship between initial IL-6 serum concentrations or its changes and severity of symptoms as a result of sarcosine addition to stable antipsychotic treatment . METHOD Fifity-eight individuals with schizophrenia with predominantly negative symptoms completed a 6-month r and omized , double-blind placebo-controlled prospect i ve study . Patients received 2 g of sarcosine ( n = 29 ) or placebo ( n = 30 ) daily per os . We measured IL-6 levels and severity of symptoms at the beginning , after 6 weeks and 6 months . As main clinical tools , we used Positive and Negative Syndrome Scale ( PANSS ) and Calgary depression scale for schizophrenia ( CDSS ) . RESULTS Augmentation with sarcosine had no effect on IL-6 serum levels in all time points . We noted significant improvements in negative symptoms , general psychopathology , and total PANSS score in the sarcosine group . We found correlation of initial serum IL-6 with severity of positive symptoms and negative association between IL-6 levels reduction and positive symptoms reduction . CONCLUSIONS Sarcosine does not significantly affect IL-6 concentrations but IL-6 may be involved in mechanisms related to the presence of positive symptoms Abstract Objectives Hypofunction of NMDA receptor is implicated in the pathophysiology , particularly cognitive impairment , of schizophrenia .  Sarcosine , a glycine transporter I ( GlyT-1 ) inhibitor , and sodium benzoate , a d-amino acid oxidase ( DAAO ) inhibitor , can both enhance NMDA receptor-mediated neurotransmission . We proposed simultaneously inhibiting DAAO and GlyT-1 may be more effective than inhibition of either in improving the cognitive and global functioning of schizophrenia patients . Methods This study compared add-on sarcosine ( 2 g/day ) plus benzoate ( 1 g/day ) vs. sarcosine ( 2 g/day ) for the clinical symptoms , as well as the cognitive and global functioning , of chronic schizophrenia patients in a 12-week , double-blind , r and omised , placebo-controlled trial . Participants were measured with the Positive and Negative Syndrome Scale and the Global Assessment of Functioning Scale every 3 weeks . Seven cognitive domains , recommended by the Measurement and Treatment Research to Improve Cognition in Schizophrenia Committee , were measured at weeks 0 and 12 . Results Adjunctive sarcosine plus benzoate , but not sarcosine alone , improved the cognitive and global functioning of patients with schizophrenia , even when their clinical symptoms had not improved . Conclusions This finding suggests N-methyl-d-aspartate receptor-enhancement therapy can improve the cognitive function of patients with schizophrenia , further indicating this pro-cognitive effect can be primary without improvement in clinical symptoms Aim : Find changes in matrix metallopeptidase-9 ( MMP-9 ) levels during augmentation of antipsychotic treatment with sarcosine and a relationship between schizophrenia symptoms severity and initial level of MMP-9 . Method : Fifty-eight patients with diagnosis of schizophrenia with predominant negative symptoms participated in a six-month prospect i ve RCT ( r and omized controlled trial ) . The patients received two grams of sarcosine ( n = 28 ) or placebo ( n = 30 ) daily . At the beginning , after six weeks and after six months MMP-9 levels were measured . Severity of symptomatology was assessed with the Positive and Negative Syndrome Scale ( PANSS ) and Calgary Depression Scale for Schizophrenia ( CDSS ) . Results : MMP-9 serum levels were stable after six weeks and six months in both groups . We noted improvement in negative symptoms , general psychopathology and total PANSS score in sarcosine group compared to placebo ; however , there was no correlations between serum MMP-9 concentrations and PANSS scores in all assessment s. Initial serum MMP-9 concentrations can not be used as an improvement predictor acquired during sarcosine augmentation . Conclusions : Our results indicate that either MMP-9 is not involved in the N-methyl-d-aspartate (NMDA)-dependent mechanism of sarcosine action in terms of clinical parameters or sarcosine induced changes in peripheral MMP-9 concentrations can not be detected in blood assessment CONTEXT Agents that enhance N-methyl-D-aspartate ( NMDA ) function through the glycine modulatory site ( D-serine , glycine , or D-cycloserine ) or through glycine transporter 1 ( sarcosine ) improve the symptoms of patients with stable chronic schizophrenia . OBJECTIVE To determine whether NMDA-glycine site agonists or glycine transporter-1 inhibitors have better efficacy and whether NMDA receptor-enhancing agents have beneficial effects for acute exacerbation of schizophrenia . DESIGN R and omized , double-blind , placebo-controlled trial . SETTING Inpatient units of 2 major medical centers in Taiwan . Patients Sixty-five schizophrenic in patients with acute exacerbation . INTERVENTIONS Six weeks of treatment with sarcosine ( 2 g/d ) , D-serine ( 2 g/d ) , or placebo and concomitant optimal risperidone therapy . MAIN OUTCOME MEASURES Positive and Negative Syndrome Scale ( PANSS ) and Scale for the Assessment of Negative Symptoms ( SANS ) ( 20 and 17 items ) total scores . RESULTS The sarcosine group revealed more reductions in PANSS total scores than the placebo ( P = .04 ) and D-serine ( P<.001 ) groups . Sarcosine adjunctive treatment was also superior to placebo in reducing SANS-20 ( P = .007 ) and SANS-17 ( P = .003 ) scores and to D-serine in decreasing SANS-20 ( P = .006 ) and SANS-17 ( P = .002 ) scores . The PANSS-general , PANSS-cognitive , and PANSS-depressive symptoms scores and SANS-alogia and SANS-blunted affect scores improved significantly more in sarcosine-cotreated patients than in risperidone monotherapy patients ( P < or = .02 for all ) . Sarcosine adjunctive therapy also surpassed D-serine in terms of PANSS-general , PANSS-positive , PANSS-negative , and PANSS-depressive symptoms scores ( P < or = .04 for all ) . D-serine and risperidone cotreatment did not differ significantly from risperidone monotherapy in all efficacy domains . CONCLUSIONS This first short-term treatment study on NMDA receptor-enhancing agents suggests that sarcosine , superior to D-serine , can benefit not only patients with long-term stable disease but also acutely ill persons with schizophrenia . This finding indicates that a glycine transporter 1 inhibitor may be more efficacious than NMDA-glycine site agonists for adjuvant treatment of schizophrenia , at least during the acute phase . Further studies are needed 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 r and omly 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 The N-methyl-d-aspartate ( NMDA ) receptor has been implicated in the pathophysiology of schizophrenia . We administered subanesthetic doses of the NMDA receptor antagonist ketamine in a double-blind , placebo – controlled design to 13 neuroleptic-free schizophrenic patients to investigate if schizophrenics will experience an exacerbation of psychotic symptoms and cognitive impairments with ketamine . We also examined whether schizophrenics experienced quantitative or qualitative differences in  ketamine  response in comparison to normal controls . Schizophrenics experienced a brief ketamine-induced  exacerbation of positive and negative symptoms with further decrements in recall and recognition memory . They also displayed greater  ketamine-induced  impairments in free recall than normals . Qualitative differences included auditory hallucinations and paranoia in patients but not in normals . These data indicate that ketamine is associated with exacerbation of core psychotic and cognitive symptoms in schizophrenia . Moreover , ketamine may differentially affect cognition in schizophrenics in comparison to normal controls BACKGROUND Small molecules that enhance the N-methyl-D-aspartate ( NMDA ) neurotransmission have been shown to be beneficial as adjuvant therapy for schizophrenia . Among these compounds , sarcosine ( a glycine transporter-I inhibitor ) , when added to an existing regimen of antipsychotic drugs , has shown its efficacy for both chronically stable and acutely ill patients . However , the efficacy of these agents as a primary antipsychotic agent has not yet been demonstrated . METHODS Twenty acutely symptomatic drug-free patients with schizophrenia were r and omly assigned under double-blind conditions to receive a 6-week trial of 2 g or 1 g of sarcosine daily . RESULTS Overall , patients in the 2-g group were more likely to respond as defined by a 20 % or more reduction of the Positive and Negative Syndrome Scale total score , particularly among antipsychotic-naïve patients . However , there was no significant between-group difference in the sarcosine dose x time interaction analysis . Both doses were well tolerated with minimal side effects . CONCLUSIONS Although patients receiving the 2-g daily dose were more likely to respond , it requires further clarification whether the effect is limited to the antipsychotic-naive population . Future placebo- or active-controlled , larger-sized studies are needed to fully assess sarcosine 's effects BACKGROUND Hypofunction of N-methyl-D-aspartate glutamate receptor had been implicated in the pathophysiology of schizophrenia . Treatment with D-serine or glycine , endogenous full agonists of the glycine site of N-methyl-D-aspartate receptor , or D-cycloserine , a partial agonist , improve the symptoms of schizophrenia . N-methylglycine ( sarcosine ) is an endogenous antagonist of glycine transporter-1 , which potentiates glycine 's action on N-methyl-D-aspartate glycine site and can have beneficial effects on schizophrenia . METHODS Thirty-eight schizophrenic patients were enrolled in a 6-week double-blind , placebo-controlled trial of sarcosine ( 2 g/d ) , which was added to their stable antipsychotic regimens . Twenty of them received risperidone . Measures of clinical efficacy and side effects were determined every other week . RESULTS Patient who received sarcosine treatment revealed significant improvements in their positive , negative , cognitive , and general psychiatric symptoms . Similar therapeutic effects were observed when only risperidone-treated patients were analyzed . Sarcosine was well-tolerated , and no significant side effect was noted . CONCLUSIONS Sarcosine treatment can benefit schizophrenic patients treated by antipsychotics including risperidone 
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The effects were correlated with increased female proportions and decreased illness duration , albeit nonsignificantly .
Conclusions : The meta- analysis suggests that sarcosine may be associated with treatment effect on overall clinical symptoms in patients with schizophrenia but not cognitive functions