***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: Cognitive deficits are rate limiters on recovery in schizophrenia that respond poorly to pharmacotherapy . Cognitive remediation therapy ( CRT ) , a novel psychological therapy , has produced promising outcomes for cognition . However , little is known about the biological mechanisms that might underlie individual differences in CRT response . Catechol-O-Methyltransferase ( COMT ) is associated specifically with prefrontal cognition . The COMT Val158Met polymorphism is known to have a functional effect on the rate of dopamine degradation , which may be related to cognitive treatment response . This study aim ed to determine whether COMT genotype influences cognitive improvement following CRT in schizophrenia . Participants with schizophrenia were recruited from three r and omised controlled trials of CRT compared to treatment as usual , and one CRT treatment only trial , each providing 40 CRT sessions .  Eighty-seven participants ( 40 % ) agreed to participate in the genetic study , and provided DNA for COMT genotyping . Cognitive function and psychopathology were assessed at baseline , post-treatment and 3 - 6-month follow-up . People with the COMT Val/Met genotype performed more poorly on categories achieved at baseline on the Wisconsin Card Sorting Test ( WCST ) than those homozygous for the Val or Met allele . Cognitive function improved with CRT but there was no association between this cognitive improvement and COMT genotype , either in the CRT group or in the total sample . The COMT val158Met polymorphism does not appear to be a clinical ly useful biomarker of cognitive improvement following CRT in schizophrenia . A complex set of factors may influence cognitive change , however , such that the COMT genotype might still have a subtle effect on response to CRT or similar interventions BACKGROUND Brain-derived neurotrophic factor ( BDNF ) is considered to be a putative biomarker for cognitive recovery in schizophrenia . However , current evidence is still scarce for pharmacological treatments , and the use of BDNF as a biomarker has only been tested once with cognitive remediation treatment ( CRT ) . METHODS A r and omized and controlled trial ( NCT02341131 ) with 70 schizophrenia out patients and 15 healthy volunteers was conducted . The participants with schizophrenia were r and omly assigned to either CRT or the control group . All the participants were assessed in terms of cognition , quality of life , and their serum BDNF levels at both baseline and after the intervention . Additionally , comparisons of the effects of the different genotypes of the Val66Met polymorphism at the BDNF gene on the outcome variables were also performed . RESULTS The patients in the CRT group presented with improvements in both cognition and quality of life . However , no significant changes were detected in the serum levels of BDNF . Interestingly , we found a significant positive interaction effect between the serum BDNF levels and the different BDNF genotypes . The Val/Val group showed significantly higher serum levels after the CRT treatment . However , the interaction among the serum BDNF levels , the BDNF genotypes and the treatment condition was not statistically significant . CONCLUSIONS The replication of the previous finding of increased serum BDNF levels after cognitive remediation in clinical ly stable individuals with schizophrenia was not achieved . However , our data indicated that genetic variability may be mediating serum BDNF activity in the context of CRT BACKGROUND A functional polymorphism of the catechol-O-methyltransferase ( COMT ) gene ( Val158Met ) partially appears to influence cognitive performance in schizophrenia subjects and healthy controls by modulating prefrontal dopaminergic activity . This study evaluated the association of the COMT Val108/158 Met genotype with response to computerized neurocognitive remediation ( CRT ) . METHOD 145 subjects with DSM-IV-TR schizophrenia or schizoaffective disorder were genotyped via saliva sampling . Subjects were evaluated on neurocognitive assessment s ( MATRICS ) and clinical symptoms ( PANSS ) at baseline and endpoint after 12weeks of CRT . " Improvement " was defined as ≥67 % of cognitive domains ( ≥4 ) showing performance increases . If ≤67 % ( ≤2 ) of domains improved , the change was defined as " minimal improvement . " A general linear model was conducted for change of each cognitive domain . RESULTS Of 145 subjects , data from 138 subjects were usable . Distribution of COMT genotype : Met/Met : 28 ( 20.29 % ) , Val/Met : 61 ( 44.20 % ) , and Val/Val : 49 ( 35.51 % ) . No significant differences were seen among genotype groups at baseline or across genotype group for " Improvement " vs. " Minimal Improvement . " GLM analysis showed significant differences in Verbal Learning ( p=0.003 ) , Visual Learning ( p=0.014 ) and Attention/Vigilance ( p=0.011 ) favoring Met/Met and Val/Met groups . CONCLUSIONS The low activity Met allele ( Met/Met ; Val/Met ) was associated with significantly greater improvements in the MATRICS domains of Verbal Learning , Visual Learning and Attention/Vigilance after CRT INTRODUCTION Schizophrenic patients present cognitive dysfunctions which are regarded to be one of endophenotypical markers predisposing to schizophrenia . Currently , schizophrenia can be treated as a neurodegenerative and neurodeveloping disease with genetic background . OBJECTIVE Assessment of the possible positive effect of neuropsychological rehabilitation in schizophrenia , in patients presenting cognitive dysfunctions . An additional aim was to verify the hypothesis that some genetic polymorphisms can be a prognostic factor for success in neuropsychological rehabilitation . MATERIAL AND METHODS 41 participants and 40 control subjects were r and omly selected . Both groups had the diagnosis of paranoid schizophrenia .  Cognitive functions were checked with the  Wisconsin Card Sorting Test , Trail Making Test , and Stroop Test at the beginning and end of the experiment . In the research group , each patient trained with the rehabilitation programme RehaCom , whereas the control group did not receive such training . Genes COMT rs4680 and BDNF rs6265 were analysed in the genetic part of study . RESULTS RehaCom procedures appear to be useful in the neuropsychological rehabilitation of cognitive dysfunctions in patients diagnosed with schizophrenia . The research group showed a moderate improvement in the training programmes . Analysis of parameters obtained in the neuropsychological tests showed a slight improvement in both groups . At the present time , analysis of the polymorphisms of genes can not be treated as a prognostic factor for the success of neuropsychological rehabilitation because statistical analyses showed few dependences with little statistical significance . CONCLUSIONS Cognitive rehabilitation produces moderate improvement in cognitive functioning Objective We previously reported the interim effects in a per protocol analysis of a r and omized controlled trial of an innovative neuroscience-informed computerized cognitive training approach in schizophrenia . Here we report the effects of training on behavioral outcome measures in our final sample using an intent-to-treat analysis . We also report the effects on serum brain-derived neurotrophic factor ( BDNF ) . Method Eighty-seven clinical ly stable participants with schizophrenia were r and omly assigned to either targeted auditory training ( AT , N=46 ) or a computer games control condition ( CG , N=41 ) . Participants were assessed on neurocognition , symptoms and functional outcome at baseline and after 50 hours of intervention delivered over 10 weeks . Serum BDNF was assessed at baseline , at 2 weeks , and at 10 weeks . Results After the intervention , AT participants showed significant gains in global cognition , speed of processing , verbal learning , and verbal memory , relative to CG participants , with no changes in symptoms or functioning . At baseline , schizophrenia participants had significantly lower-than-normal serum BDNF . AT participants showed a significant increase in serum BDNF compared to CG participants , and “ normalized ” levels by post training . Conclusions Participants with chronic schizophrenia made significant cognitive gains after 50 hours of intensive computerized training delivered as a st and -alone treatment , but no improvement in symptoms or functioning . Serum BDNF levels were significantly increased , and may serve as a peripheral biomarker for the effects of training . Future research must focus on : 1 ) Methods of integrating cognitive training with psychosocial treatments ; 2 ) A deeper underst and ing of underlying neurophysiology in order to enhance critical mechanisms of action OBJECTIVE Deficits in working memory and in prefrontal cortical physiology are important outcome measures in schizophrenia , and both have been associated with dopamine dysregulation and with a functional polymorphism ( Val(108/158)Met ) in the catechol O-methyltransferase ( COMT ) gene that affects dopamine inactivation in the prefrontal cortex . The purpose of the present study was to evaluate in patients with schizophrenia the effect of COMT genotype on symptom variation , working memory performance , and prefrontal cortical physiology in response to treatment with an atypical antipsychotic drug . METHOD Thirty patients with acute untreated schizophrenia were clinical ly evaluated with the Positive and Negative Syndrome Scale , underwent COMT Val/Met genotyping , and entered an 8-week prospect i ve study of olanzapine treatment . Twenty patients completed two 3-T functional magnetic resonance imaging scans at 4 and 8 weeks during performance of N-back working memory tasks . RESULTS There was a significant interaction of COMT genotype and the effects of olanzapine on prefrontal cortical function . Met allele load predicted improvement in working memory performance and prefrontal physiology after 8 weeks of treatment . A similar effect was found also for negative symptoms assessed with the Positive and Negative Syndrome Scale . CONCLUSIONS These results suggest that a genetically determined variation in prefrontal dopamine catabolism impacts the therapeutic profile of olanzapine OBJECTIVES The aim of this study was to evaluate the impact of computer-assisted " drill- and - strategy " cognitive remediation ( CR ) for community-dwelling individuals with schizophrenia on cognition , everyday self-efficacy , and independent living skills . METHODS Fifty-six people with schizophrenia or schizoaffective disorder were r and omized into CR or computer game ( CG ) playing ( control ) , and offered twenty 1-hr individual sessions in a group setting over 10 weeks . Measures of cognition , psychopathology , self-efficacy , quality of life , and independent living skills were conducted at baseline , end-group and 3 months following intervention completion . RESULTS Forty-three participants completed at least 10 sessions and the end-group assessment . Linear mixed-effect analyses among completers demonstrated a significant interaction effect for global cognition favoring CR ( p=.028 ) . CR-related cognitive improvement was sustained at 3-months follow-up . At end-group , 17 ( 77 % ) CR completers showed a reliable improvement in at least one cognitive domain . A significant time effect was evident for self-efficacy ( p=.028 ) with both groups improving over time , but no significant interaction effect was observed . No significant effects were found for other study outcomes , including the functional measure . CONCLUSIONS Computer-assisted drill- and - strategy CR in schizophrenia improved cognitive test performance , while participation in both CR and CG playing promoted enhancements in everyday self-efficacy . Changes in independent living skills did not appear to result from CR , however . Adjunctive psychosocial rehabilitation is likely necessary for improvements in real-world community functioning to be achieved . ( JINS , 2018 , 24 , 549 - 562 ) Neurocognitive deficits are recognized as core features of schizophrenia and have a great impact on functional outcome . Recent reports have suggested that a functional polymorphism , Val158Met , of the catechol-O-methyltransferase ( COMT ) gene , partially influences cognitive performances ( mainly cognitive flexibility and working memory ) both in schizophrenic patients and in healthy controls , probably by modulating prefrontal dopamine function . While previous studies focused on single evaluation of cognitive functioning , we aim ed to analyse the additive effect of COMT genotype and cognitive exercise on dynamic modulation of cognitive performances . We analysed the COMT Val158Met polymorphism in 50 patients with chronic schizophrenia r and omly allocated to two treatment conditions for 3 months : st and ard rehabilitation treatment ( SRT ) alone and SRT plus specific cognitive exercise of impaired functions . We then divided our sample in four subgroups on the basis of genotype ( Val/Val versus Met carriers ) and treatment ( placebo versus active ) . We assessed patients with a neuropsychological battery , the Positive and Negative Symptoms Scale ( PANSS ) and the Quality of Life Scale ( QLS ) at enrolment , after 3 months of therapy and after further 3 months of follow-up . We found significantly greater improvement of cognitive flexibility performance and QLS total score for Met carriers on active treatment in comparison to Val/Val on placebo . The findings support the hypothesis that COMT polymorphism influences individual capacity to recover from cognitive deficit through rehabilitation therapy after a wider intervention also including deficit-specific cognitive exercise as a potentiating tool Neurocognition is moderately to severely impaired in patients with schizophrenia . However , the factor structure of the various neurocognitive deficits , the relationship with symptoms and other variables , and the minimum amount of testing required to determine an adequate composite score has not been determined in typical patients with schizophrenia . An ‘ all- 
    Output:
    
Eventually , promising results showing a relationship between some phenotypic variations based on different polymorphisms and different levels of responsivity to cognitive remediation therapies  have been described although results are still inconclusive .