***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 The relationship between cognition and outcome in people with schizophrenia has been established in studies that , for the most part , examined chronic patients and were cross-sectional in design . The purpose of this study was to analyze the relationships between neurocognitive variables assessed at illness onset and functional outcome in a longitudinal design . An additional area of interest was whether the severity of negative symptoms would predict outcome independently from neurocognitive variables or whether there would be an overlap in their predictive power . METHOD The authors administered a comprehensive cognitive battery and clinical assessment s to 99 subjects who were in their first episode of illness and analyzed the relationship of cognition and symptom severity at intake with community outcome after an average follow-up period of 7 years . RESULTS Verbal memory , processing speed and attention , and the severity of negative symptoms at intake were related to subsequent outcome . Global psychosocial functioning was predicted by negative symptoms and attention . Verbal memory was the significant predictor of the degree of impairment in recreational activities . Impairment in relationships was predicted by negative symptoms and memory , whereas attention and negative symptoms were predictive of work performance . There was an overlap in the variance in outcome explained by cognitive variables and negative symptoms . CONCLUSIONS Verbal memory and processing speed and attention are potential targets for psychosocial interventions to improve outcome . Results from cross-sectional or chronic patient studies do not necessarily correspond to the findings of this prospect i ve first-episode study in which cognition appears to explain less of the variance in outcome 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 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 Potency equivalents for anti-psychotic drugs are required to guide clinical dosing and for design ing and interpreting research studies . Available dosing guidelines are limited by the methods and data from which they were generated . METHOD With a two-step Delphi method , the authors surveyed a diverse group of international clinical and research experts , seeking consensus regarding antipsychotic dosing . The authors determined median clinical dosing equivalents and recommended starting , target range , and maximum doses for 61 drugs , adjusted for selected clinical circumstances . RESULTS Participants ( N=43 ) from 18 countries provided dosing recommendations regarding treatment of psychotic disorders for 37 oral agents and 14 short-acting and 10 long-acting parenteral agents . With olanzapine 20 mg/day as reference , estimated clinical equivalency ratios of oral agents ranged from 0.025 for sulpiride to 10.0 for trifluperidol . Seventeen patient and treatment characteristics , including age , hepatic and renal function , illness stage and severity , sex , and diagnosis , were associated with dosing modifications . CONCLUSIONS In the absence of adequate prospect i ve , r and omized drug-drug comparisons , the present findings provide broad , international , expert consensus-based recommendations for most clinical ly employed antipsychotic drugs . They can support clinical practice , trial design , and interpretation of comparative antipsychotic trials 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 for moderate to severe negative symptoms without marked positive , depressive , or extrapyramidal symptoms . The primary outcome measures were the average " rate of change " of Scale for the Assessment of Negative Symptoms ( SANS ) total scores and change in the average cognitive domain z scores . RESULTS There were no significant differences in change in the SANS total score between glycine and placebo subjects or D-cycloserine and placebo subjects . A prespecified test for the site-by-treatment-by-time interaction was significant in post hoc tests . One site had greater reduction in the SANS total score for patients receiving D-cycloserine relative to patients receiving placebo . A second site had greater reduction in the SANS total score for placebo patients compared with glycine patients . There were no significant differences between glycine and placebo or D-cycloserine and placebo subjects on the average cognition z score . CONCLUSIONS The study results suggest that neither glycine nor D-cycloserine is a generally effective therapeutic option for treating negative symptoms or cognitive impairments CONTEXT Cognitive impairment in schizophrenia is frequent , involves multiple domains , and is enduring . Numerous recent clinical trials have suggested that second-generation antipsychotic medications significantly enhance cognition in schizophrenia . However , none of these studies included healthy controls undergoing repeated testing to assess the possibility that improvements might reflect simple practice effects . OBJECTIVE To report the results on cognition of a r and omized comparison of 2 widely prescribed second-generation antipsychotic medications , olanzapine and risperidone , in patients with first-episode schizophrenia and a healthy control group . DESIGN R and omized clinical trial . SETTING Hospital-based research units . Patients A total of 104 participants with first-episode schizophrenia and 84 healthy controls . MAIN OUTCOME MEASURES Cognitive assessment of all study participants occurred at baseline , 6 weeks later , and 16 weeks later . Neurocognitive tests included measures of working memory and attention , speed , motor function , episodic memory , and executive function . RESULTS No differential drug effects were observed . Of 16 cognitive measures , 9 demonstrated improvement over time and only 2 demonstrated greater rates of change than those observed in the healthy control group undergoing repeated assessment . The composite effect size for cognitive change was 0.33 in the healthy control group ( attributed to practice ) and 0.36 in the patients with first-episode schizophrenia . Improvements in cognition in the first-episode schizophrenia group could not be accounted for by medication dose , demographic variables , or intellectual level . CONCLUSIONS The cognitive improvements observed in the trial were consistent in magnitude with practice effects observed in healthy controls , suggesting that some of the improvements in cognition in the first-episode schizophrenia group may have been due to practice effects ( ie , exposure , familiarity , and /or procedural learning ) . Our results also indicated that differential medication effects on cognition were small . We believe that these findings have important implication s for drug discovery and the design of registration trials that attempt to demonstrate cognitive enhancement BACKGROUND Brain glutath 
    Output:
    
Subgroup analyses by diagnosis ( schizophrenia only studies ) , concomitant antipsychotics , or pathway of drugs to enhance the glutamatergic neurotransmission ( glycine allosteric site of NMDA receptors or α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors ) suggested no procognitive effect  of glutamate positive modulators .
Further , no effect was found in individual compounds on cognition .
In conclusion , glutamate positive modulators may not be effective in reversing overall cognitive impairments in patients with schizophrenia as adjunctive therapies