***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: BACKGROUND Targeting glutamatergic dysfunction provides an exciting opportunity to improve cognitive impairment in schizophrenia . One treatment approach has targeted inadequate antioxidant defenses at glutamatergic synapses . Animal and human data suggest NMDA antagonists worsen executive cognitive controls -- e.g . increase perseverative responses and impair set-shifting . We conducted a preliminary study to test the hypothesis that L-carnosine , an antioxidant and anti-glycation agent which is co-localized and released with glutamate would improve executive dysfunction , a cognitive domain associated with glutamate . METHODS Seventy-five symptomatically stable adults with chronic schizophrenia were r and omly assigned to L-carnosine as adjunctive treatment ( 2 g/day ) or a matched placebo in a double-blind manner for 3 months . Cognitive domains ( executive dysfunction , memory , attention and motor speed ) were assessed using a computerized battery at baseline , 4 and 12 weeks , along with psychopathology ratings and safety parameters . RESULTS The L-carnosine group performed significantly faster on non-reversal condition trials of the set-shifting test compared with placebo but reversal reaction times and errors were not significantly different between treatments . On the strategic target detection test , the L-carnosine group displayed significantly improved strategic efficiency and made fewer perseverative errors compared with placebo . Other cognitive tests showed no significant differences between treatments . Psychopathology scores remained stable . The carnosine group reported more adverse events ( 30 % ) compared with the placebo group ( 14 % ) . Laboratory indices remained within acceptable ranges . CONCLUSIONS These preliminary findings suggest that L-carnosine merits further consideration as adjunctive treatment to improve executive dysfunction in persons with schizophrenia Abstract Biomarker-guided treatments are needed in psychiatry , and previous data suggest oxidative stress may be a target in schizophrenia . A previous add-on trial with the antioxidant N-acetylcysteine ( NAC ) led to negative symptom reductions in chronic patients . We aim to study NAC ’s impact on symptoms and neurocognition in early psychosis ( EP ) and to explore whether glutathione (GSH)/redox markers could represent valid biomarkers to guide treatment . In a double-blind , r and omized , placebo-controlled trial in 63 EP patients , we assessed the effect of NAC supplementation ( 2700 mg/day , 6 months ) on PANSS , neurocognition , and redox markers ( brain GSH [ GSHmPFC ] , blood cells GSH levels [ GSHBC ] , GSH peroxidase activity [ GPxBC ] ) . No changes in negative or positive symptoms or functional outcome were observed with NAC , but significant improvements were found in favor of NAC on neurocognition ( processing speed ) . NAC also led to increases of GSHmPFC by 23 % ( P = .005 ) and GSHBC by 19 % ( P = .05 ) . In patients with high-baseline GPxBC compared to low-baseline GPxBC , subgroup explorations revealed a link between changes of positive symptoms and changes of redox status with NAC . In conclusion , NAC supplementation in a limited sample of EP patients did not improve negative symptoms , which were at modest baseline levels . However , NAC led to some neurocognitive improvements and an increase in brain GSH levels , indicating good target engagement . Blood GPx activity , a redox peripheral index associated with brain GSH levels , could help identify a subgroup of patients who improve their positive symptoms with NAC . Thus , future trials with antioxidants in EP should consider biomarker-guided treatment 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 BACKGROUND It is difficult to improve negative symptoms and cognitive impairments in schizophrenia . A previous pilot study has shown that minocycline , a semi-synthetic second-generation tetracycline , is effective in treating for negative and /or cognitive symptoms in schizophrenia . OBJECTIVES The present study was design ed to examine the efficacy and safety of minocycline for the treatment of negative symptoms and cognitive impairments in patients with schizophrenia . METHODS Ninety-two patients with early stage schizophrenia treated with risperidone  entered this 16-week , double blind , r and omized , placebo-controlled clinical trial . Subjects were r and omly assigned to receive minocycline ( 200 mg per day ) or the placebo . The primary outcome was evaluated using the Scale for the Assessment of Negative Symptoms ( SANS ) . Secondary outcomes included the response rate of SANS , the Positive and Negative Syndrome Scale ( PANSS ) , the Clinical Global Impression Scale ( CGI ) , and cognitive tests . RESULTS Subjects receiving minocycline had greater improvements on SANS total scores and PANSS negative subscale scores ( P<0.001 ) when compared with those receiving the placebo . Rates of treatment response ( 43.6 % ) in the minocycline group were significantly higher than those in the placebo group ( 10.0 % ) after 16weeks of treatment . There was no significant difference between the seven cognitive domains ( P>0.05 ) , except for the attention domain ( P=0.044 ) . CONCLUSIONS The addition of minocycline to atypical antipsychotic drugs in early schizophrenia had significant efficacy on negative symptoms but had a slight effect on the attention domains of patients with schizophrenia . It may be considered as a new adjunct treatment for negative symptoms of schizophrenia . Clinical trials.gov identifier : NCT01493622 BACKGROUND Hypofunction of N-methyl-D-aspartate ( NMDA ) subtype glutamate receptor has been implicated in the pathophysiology of schizophrenia .  D-serine is a full agonist of the glycine site of NMDA receptor , an endogenous cotransmitter enriched in corticolimbic regions and distributed in parallel with NMDA receptor . Supplementation of D-serine may improve the symptoms of schizophrenia . METHODS Thirty-one Taiwanese schizophrenic patients enrolled in a 6-week double-blind ,  placebo-controlled trial of D-serine ( 30 mg/kg/day )  , which was added to their stable antipsychotic regimens . Of these , 28 completed the trial .  Measures of clinical efficacy , side effects , and serum levels of amino acids and D-serine  were determined every other week .  Wisconsin Card Sorting Test ( WCST ) was performed at the beginning and end of the trial . RESULTS Patients who received D-serine treatment revealed significant improvements in their positive , negative , and cognitive symptoms as well as some performance in WCST . D-serine levels at week 4 and 6 significantly predicted the improvements . D-serine was well tolerated and no significant side effects were noted . CONCLUSIONS The significant improvement with the D-serine further supports the hypothesis of NMDA receptor hypofunction in schizophrenia . Given the effects of D-serine on positive symptoms , a trial of D-serine alone in schizophrenia should be considered The combination of pharmacotherapy and cognitive retraining ( CRT ) for the cognitive deficits of schizophrenia may be more efficacious than either approach alone , but this has not yet been tested . This study evaluated the feasibility , safety , tolerability , and efficacy of 12 weeks of D-serine , combined with CRT in the treatment of cognitive deficits in schizophrenia at two academic sites in parallel , in India and the United States . In a r and omized , partial double-blind , placebo-controlled , parallel-group design , 104 schizophrenia subjects ( US site=22 , Indian site=82 ) were r and omized to : ( 1 ) D-serine ( 30 mg/kg)+CRT ( 5 h/week ) , ( 2 ) D-serine+control CRT , ( 3 ) CRT+placebo D-serine , and ( 4 ) placebo+control CRT . Completion rates were 84 and 100 % in the Indian and US sample s , respectively . On various outcome measures of safety and tolerability , the interventions were well tolerated .  D-Serine and CRT did not show any significant effect on the Global Cognitive Index , although both interventions showed differential site effects on individual test performance . CRT result ed in a significant improvement in Verbal Working Memory , and a trend toward improvement in Attention/Vigilance . This is the first study to demonstrating the feasibility , safety , and tolerability of combination pharmacotherapy and CRT in a multicenter international clinical trial . These preliminary findings provide support for future studies using higher doses of D-serine that have been shown to be efficacious or other pharmacotherapies , along with the newer cognitive remediation strategies that are individualized and that target basic information processing Objective Clozapine is the most effective antipsychotic for treatment refractory people with schizophrenia , yet many patients only partially respond . Accumulating pre clinical and clinical data suggest benefits with minocycline . We tested adjunct minocycline to clozapine in a 10-week , double-blind , placebo-controlled trial . Primary outcomes tested were positive , and cognitive symptoms , while avolition , anxiety/depression , and negative symptoms were secondary outcomes . Methods Schizophrenia and schizoaffective participants ( n = 52 ) with persistent positive symptoms were r and omized to receive adjunct minocycline ( 100 mg oral capsule twice daily ; n = 29 ) or placebo ( n = 23 ) . Results Brief Psychiatric Rating Scale ( BPRS ) psychosis factor ( P = 0.098 ; effect size [ ES ] , 0.39 ) and BPRS total score ( P = 0.075 ; ES , 0.55 ) were not significant . A change in total BPRS symptoms of more than or equal to 30 % was observed in 7 ( 25 % ) of 28 among minocycline and 1 ( 4 % ) of 23 among placebo participants , respectively ( P = 0.044 ) . Global cognitive function ( MATRICS Consensus Cognitive Battery ) did not differ , although there was a significant variation in size of treatment effects among cognitive domains ( P = 0.03 ) , with significant improvement in working memory favoring minocycline ( P = 0.023 ; ES , 0.41 ) . The Scale for the Assessment of Negative Symptoms total score did not differ , but significant improvement in avolition with minocycline was noted ( P = 0.012 ; ES , 0.34 ) . Significant improvement in the BPRS anxiety/depression factor was observed with minocycline ( P = 0.028 ; ES , 0.49 ) . Minocycline was well tolerated with significantly fewer headaches and constipation compared with placebo . Conclusions Minocycline 's effect on the MATRICS Consensus Cognitive Battery composite score and positive symptoms were not statistically significant . Significant improvements with minocycline were seen in working memory , avolition , and anxiety/depressive symptoms in a chronic population with persistent symptoms . Larger studies are needed to vali date these findings OBJECTIVE Patients with schizophrenia frequently present with negative symptoms and cognitive impairments for which no effective treatments are known . Agents that act at the glycine site of the N-methyl-D-aspartic acid ( NMDA ) glutamatergic receptor have been suggested as promising treatments for moderate to severe negative symptoms and cognitive impairments . METHOD The Cognitive and Negative Symptoms in Schizophrenia Trial ( CONSIST ) was a 16-week double-blind , double-dummy , parallel group , r and omized clinical trial of adjunctive glycine , D-cycloserine , or placebo conducted at four sites in the United States and one site in Israel . The participants were 157 in patients and out patients who met DSM-IV criteria for schizophrenia or schizoaffective disorder and retrospective and prospect i ve criteria 
    Output:
    
Men were associated with a smaller effect of NMDA-receptor-positive modulators on overall cognitive function .
Conclusions : Our meta- analysis revealed no significant effect of NMDA-enhancing agents  on overall cognition .
However , subgroup analysis suggested that NMDAR-enhancing agents may benefit young patients with schizophrenia , and NAC may have an effect on working memory .