***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 : Schizophrenia has been associated with disturbances of thalamic functioning . In light of recent evidence suggesting a significant impact of the glutamatergic system on key symptoms of schizophrenia , we assessed whether modulation of the glutamatergic system via blockage of the N-methyl-d-aspartate (NMDA)-receptor might lead to changes of thalamic functional connectivity . Methods : Based on the ketamine model of psychosis , we investigated changes in cortico-thalamic functional connectivity by intravenous ketamine challenge during a 55-minute resting-state scan . Thirty healthy volunteers were measured with pharmacological functional magnetic resonance imaging using a double-blind , r and omized , placebo-controlled , crossover design . Results : Functional connectivity analysis revealed significant ketamine-specific changes within the thalamus hub network , more precisely , an increase of cortico-thalamic connectivity of the somatosensory and temporal cortex . Conclusions : Our results indicate that changes of thalamic functioning as described for schizophrenia can be partly mimicked by NMDA-receptor blockage . This adds substantial knowledge about the neurobiological mechanisms underlying the profound changes of perception and behavior during the application of NMDA-receptor antagonists Background Dysfunction of neuroplasticity due to N-methyl-d-aspartate ( NMDA ) receptor hypofunction may be a causal factor for memory and executive dysfunctioning in schizophrenia . Deregulation of NMDA transmission in the prefrontal cortex may also explain negative and positive symptoms . Clozapine augmentation with memantine targets altered NMDA receptor-mediated neurotransmission in schizophrenia and showed substantial beneficial effects on several symptom domains in a small proof-of-concept study . We evaluate effects of memantine add-on treatment to clozapine for memory and executive function , and negative and positive symptoms in schizophrenia . Method  Clozapine-treated patients with refractory schizophrenia were r and omly assigned to 12 weeks of double-blind adjunctive treatment with memantine  ( n = 26 ) or placebo  ( n = 26 ) . Crossover occurred after a 2-week placebo wash-out period . Primary endpoints were change from baseline to 12 weeks treatment and 14 weeks to 26 weeks treatment on memory and executive function using the Cambridge Neuropsychological Test Automated Battery ( CANTAB ) , Positive and Negative Syndrome Scale ( PANSS ) , and Clinical Global Impression Severity Scale ( CGI-S ) . Side effects were assessed using the Liverpool University Neuroleptic Side-Effect Rating Scale . Results When compared with placebo , memantine improved a composite memory score comprising verbal recognition memory and paired associates learning task scores on the CANTAB ( effect size = 0.30 ) and PANSS negative subscale score ( effect size = 0.29 ) . Side effects were mild and transient . Conclusions In patients with clozapine-treated refractory schizophrenia , memantine addition significantly improved verbal and visual memory and negative symptoms without serious adverse effects . These results justify further investigations on long-term memantine augmentation to clozapine in treatment-resistant schizophrenia The " glutamate hypothesis of schizophrenia " has changed attitudes in the development of new medications . This study aim ed to evaluate the effects of 20 mg of memantine per day ( as a NMDA receptor antagonist ) added to risperidone among male patients with schizophrenia . In a r and omized placebo-controlled , double-blind clinical trial , 46 adult male patients with schizophrenia were evaluated in both intervention and control groups at weeks 0 , 6 and 12 . The positive and negative symptoms scale and the mini mental status examination were used to assess positive , negative and cognitive symptoms and general psychopathology . The mean age of the patients was 44.8 for the intervention group and 45.3 for the control group , and the mean times since diagnosis were 23.5 and 25.7 years in the intervention and the control group , respectively .  Positive and general psychopathologic symptoms showed no significant differences between the two groups at baseline or after treatment ; while negative symptoms improved significantly in the intervention group at week 12 . Cognitive function was also significantly improved in the intervention group at weeks 6 and 12 . Memantine is supported as an effective adjunct treatment to improve negative and cognitive symptoms in patients with schizophrenia Rationale Pro-cognitive agents for chronic psychotic disorders ( CPDs ) might be detected via experimental medicine models , in which neural targets engaged by the drug predict sensitivity to the drug ’s pro-cognitive effects . Objective This study aims to use an experimental medicine model to test the hypothesis that “ target engagement ” predicts pro-cognitive effects of the NMDA antagonist , memantine ( MEM ) , in CPDs . Methods MATRICS Consensus Cognitive Battery ( MCCB ) performance was assessed in CPD ( n = 41 ) and healthy subjects ( HS ; n = 41 ) in a double-blind , r and omized cross-over design of acute ( single dose ) MEM ( placebo vs. 10 or 20 mg p.o . ) . Measures of prepulse inhibition ( PPI ) and mismatch negativity previously reported from this cohort substantiated target engagement . Biomarkers predicting MEM neurocognitive sensitivity were assessed . Results Testing confirmed MCCB deficits associated with CPD diagnosis , age , and anticholinergic exposure . MEM ( 20 mg p.o . ) reduced MCCB performance in HS . To control for significant test order effects , an “ order-corrected MEM effect ” ( OCME ) was calculated . In CPD subjects , greater age , positive MEM effects on PPI , and SNP rs1337697 ( within the ionotropic NMDA receptor gene , GRIN3A ) predicted greater positive OCME with 20 mg MEM . Conclusions An experimental medicine model to assess acute pro-cognitive drug effects in CPD subjects is feasible but not without challenges . A single MEM 20 mg dose had a negative impact on neurocognition among HS . In CPD patients , age , MEM effects on PPI , and rs1337697 predicted sensitivity to the neurocognitive effects of MEM . Any potential clinical utility of these predictive markers for pro-cognitive effects of MEM in subgroups of CPD patients can not be inferred without a validating clinical trial BACKGROUND Glutamate deregulation may be involved in the neuropathology of schizophrenia , mainly through N-methyl-d-aspartate ( NMDA ) receptor dysfunction . Memantine , a drug approved by the FDA for the treatment of moderate to severe Alzheimer 's disease , acts as a weak nonselective NMDA receptor antagonist . The aim of this study was to examine the efficacy of memantine as an adjunctive treatment to clozapine in patients with refractory schizophrenia . METHOD In this double-blind , placebo-controlled study , out patients with refractory schizophrenia according to DSM-IV clinical criteria were r and omly assigned , from March 2005 to February 2008 , to receive either 20 mg/d memantine ( n = 10 ) or placebo ( n = 11 ) , in addition to clozapine , for 12 weeks . The primary outcome measure was the total score on the 18-item Brief Psychiatry Rating Scale ( BPRS ) and BPRS subscales of positive and negative symptoms . Secondary outcomes were global severity of disease as measured by the Clinical Global Impressions scale ( CGI ) , cognition as assessed by the Mini-Mental State Examination ( MMSE ) , and extrapyramidal symptoms as assessed by the Simpson-Angus Scale ( SAS ) . RESULTS Twenty-one participants completed the study and were used in the analysis . Significant improvement ( P < .01 ) on the total BPRS score , its subscales of positive ( effect size [ ES ] = -1.38 ) and negative ( ES = -3.33 ) symptoms , the CGI score ( ES = 1.56 ) , and the MMSE score was observed with memantine as compared with placebo . No significant changes in extrapyramidal symptoms were observed . CONCLUSIONS Memantine add-on to clozapine therapy was associated with improvement in negative and positive symptoms in refractory schizophrenia patients . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00757978 Glutamate dysregulation may be involved in the neuropathology of schizophrenia .  Memantine , a drug approved by the FDA for the treatment of moderate to severe Alzheimer 's disease , acts as a partial uncompetitive NMDA receptor antagonist . The aim of this study was to examine the efficacy of memantine as an adjunctive treatment to olanzapine in patients with schizophrenia . In this double-blind , placebo-controlled studies , patients with schizophrenia according to DSM-IV clinical criteria were selected . Patients were r and omly assigned to receive either memantine ( week 1:10 mg/day ; weeks 2 - 6:20 mg/day ) plus olanzapine ( 15 - 20 mg/day ) or olanzapine plus placebo . At baseline , no statistically significant difference regarding the mean total PANSS scores between treatment groups was found . Results showed that memantine significantly improved the positive and negative PANSS score in patients maintained on olanzapine after six weeks compared to olanzapine alone ( P<0.001 ) . Furthermore , female patients showed significantly better response than males , especially in positive PANSS score . No significant changes in extrapyramidal symptoms were observed . These findings indicate that  olanzapine efficacy might be augmented with memantine . Furthermore , this effect is more remarkable in female patients with schizophrenia Background : Schizophrenia severely influences function and quality of life . The benefit of newer antipsychotics in improving the quality of life in schizophrenia still remains controversial . The aim of the present study is to evaluate the effect of memantine on global function and quality of life in patients with schizophrenia . Material s and Methods : This was a r and omized controlled trial on inpatient cases of schizophrenia in Noor University Hospital , Isfahan , Iran . A number of 64 patients were selected through sequential sampling ; patients were r and omly allocated in intervention and placebo groups . The intervention group was treated with memantine plus previously administered , stabled-dose , atypical antipsychotic , while the control group received placebo plus previously administered , stabled-dose , atypical antipsychotic . Memantine administration was initiated at 5 mg daily ; the dosage was increased at weekly intervals by 5 mg and finally up-titrated to 20 mg daily within 4 weeks . All patients were assessed by means of Global Assessment of Functioning ( GAF ) and quality of life scale ( QLS ) initially and every four weeks to the end of the 12th week . Results : Analysis of baseline GAF and QLS scores showed no significant differences between the two groups ( P = 0.081 and P = 0.225 , respectively ) . GAF and QLS scores increased in both groups ; but it was higher in the intervention group . The difference between the two groups was statistically significant . ( P < 0.001 and P < 0.001 , respectively ) memantine was well tolerated , with no significant side effects . Conclusion : Add-on memantine was significantly effective in improving the global function of patients  as well as their quality of life Abstract We aim ed to evaluate the efficacy of memantine add-on in the treatment of primary negative symptoms of patients with stable schizophrenia . In a double-blind placebo-controlled clinical trial , 40 patients with schizophrenia ( Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition ) who were stabilized on risperidone for a minimum of 8 weeks were r and omized to either memantine ( 20 mg ) or placebo in addition to risperidone , 6 mg/d , for eight weeks . Assessment was done using the Positive and Negative Syndrome Scale at baseline , week 4 , and week 8 . The Hamilton Depression Rating Scale and the Extrapyramidal Symptom Rating Scale at baseline and week 8 were used to assess depression and extrapyramidal symptoms , respectively . All 40 patients had at least one postbaseline measurement , and 38 patients completed the trial . Patients in the memantine group showed a significantly greater improvement on negative subscale than the placebo group at end point ( P < 0.001 ) . The same effect was observed for the total score ( P < 0.001 ) and the general psychopathology subscale score ( P = 0.002 ) . There was no significant difference in reduction of positive symptoms score between the 2 groups ( P = 0.757 ) . Changes in the Hamilton Depression Rating Scale and the Extrapyramidal Symptom Rating Scale scores and frequency of adverse effects did not differ between the 2 groups . Our study showed that memantine is a tolerable and efficacious add-on treatment for primary negative symptoms of schizophrenia 
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Conclusions Memantine add-on treatment may be beneficial for treating psychopathological symptoms ( especially negative symptoms ) in schizophrenia patients .
The negative-symptom effect size may be associated with younger adult schizophrenia patients