***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: Genetic  risk prediction  has several potential applications in medical research and clinical practice and could be used , for example , to stratify a heterogeneous population of patients by their predicted genetic risk . However , for polygenic traits , such as psychiatric disorders , the accuracy of risk prediction is low . Here we use a multivariate linear mixed model and apply multi-trait genomic best linear unbiased prediction for genetic risk prediction . This method exploits correlations between disorders and simultaneously evaluates individual risk for each disorder . We show that the multivariate approach significantly increases the prediction accuracy for schizophrenia , bipolar disorder , and major depressive disorder in the discovery as well as in independent validation data sets . By grouping SNPs based on genome annotation and fitting multiple r and om effects , we show that the prediction accuracy could be further improved . The gain in prediction accuracy of the multivariate approach is equivalent to an increase in sample size of 34 % for schizophrenia , 68 % for bipolar disorder , and 76 % for major depressive disorders using single trait models . Because our approach can be readily applied to any number of GWAS data sets of correlated traits , it is a flexible and powerful tool to maximize prediction accuracy . With current sample size , risk predictors are not useful in a clinical setting but already are a valuable research tool , for example in experimental design s comparing cases with high and low polygenic risk BACKGROUND Cognitive impairment in schizophrenia-spectrum disorders is highly prevalent and notably influences functional outcomes . AIMS To characterise the cognitive effectiveness of second-generation antipsychotic drugs . METHOD One hundred consecutive and previously unmedicated patients with first-episode schizophrenia-spectrum disorders were admitted . Seventy-seven completed baseline , 1-month and 6-month psychopathological and neuropsychological assessment s. Patients were r and omised to risperidone or olanzapine treatment . Four final treatment allocation groups were defined since patients continued treatment in their normal setting : risperidone , olanzapine , mixed and no-antipsychotic groups . RESULTS There were no differences in cognitive effectiveness between the four treatment groups . Reliable change index methods demonstrated that nearly a half of patients showed an improvement in Global Cognitive Score at the 6-month assessment . Improvement on the neuropsychological tests ranged from 17 to 54 % . A strong predictor of cognitive response was poor performance on baseline neuropsychological tests ; response was moderately influenced by a low premorbid scholastic performance and IQ . CONCLUSIONS Cognitive improvement related to second-generation antipsychotic drugs appeared within the first 4 weeks of treatment and persisted at 6 months irrespective of treatment group . Greater cognitive dysfunction at baseline and lower premorbid cognitive background predicted cognitive improvement in our sample BACKGROUND The purpose of this investigation was to test the efficacy of novel antipsychotic medications in the treatment of  cognitive impairment in early phase schizophrenia . METHODS Sixty-five patients in this multicenter double-blind study were r and omly assigned to olanzapine ( 5 - 20 mg ) , risperidone ( 4 - 10 mg ) , or haloperidol ( 5 - 20 mg ) . St and ard measures of clinical and motor syndromes were administered , as well as a comprehensive battery of tests to assess ( 1 ) motor skills , ( 2 ) attention span , ( 3 ) verbal fluency and reasoning , ( 4 ) nonverbal fluency and construction , ( 5 ) executive skills , and ( 6 ) immediate recall at baseline and after 6 , 30 , and 54 weeks of treatment . RESULTS The general cognitive index derived from the 6 domain scores revealed a significantly greater benefit from treatment with olanzapine relative to haloperidol and olanzapine relative to risperidone , but no significant difference was shown between risperidone and haloperidol . The improvement related to olanzapine was apparent after 6 weeks and enhanced after 30 and 54 weeks of treatment . Exploratory within-group analyses of the 6 cognitive domains after a conservative Bonferroni adjustment revealed a significant improvement with olanzapine only on the immediate recall domain , and similar analyses of the 17 individual tests revealed a significant improvement with olanzapine only on the Hooper Visual Organization Test . CONCLUSIONS These data suggest that olanzapine has some superior cognitive benefits relative to haloperidol and risperidone . A larger sample replication study is necessary to confirm and generalize the observations of this study and begin evaluation of the implication s of this change to cerebral function and quality of life for people with schizophrenia The study investigated the non-inferiority of flupentixol compared to risperidone in the treatment of negative symptoms . In addition , the effects of flupentixol on mood and cognitive symptoms were explored . In a r and omized , double-blind multicenter study , 144 non-acute schizophrenia patients with predominant negative symptoms were treated with a flexible dose of either flupentixol ( 4 - 12 mg/d ) or risperidone ( 2 - 6 mg/d ) for up to 25 weeks . In addition to a non-inferiority analysis , a principal component analysis ( PCA ) of the PANSS was performed post hoc . Regarding negative symptoms , flupentixol proved to be non-inferior to risperidone . Both drugs improved depressed mood with effect sizes favoring flupentixol . PCA suggested a five-factor structure . Effect sizes for the cognitive factor were up to 0.74 for flupentixol and up to 0.80 for risperidone .  EPS scores were rather low and Parkinsonism improved in both groups , but anticholinergic drugs were prescribed significantly more frequently in the flupentixol group , which generally showed significantly more adverse events . Results indicate that the 1st generation antipsychotic flupentixol  improves negative , affective and cognitive symptoms in chronic schizophrenia comparable to risperidone . Further studies should confirm the latter using neuropsychological performance tests and should investigate whether tolerability improves with a markedly lower dose range OBJECTIVE Newer antipsychotic drugs have shown promise in ameliorating neurocognitive deficits in patients with schizophrenia , but few studies have compared newer antipsychotic drugs with both clozapine and conventional agents , particularly in patients who have had suboptimal response to prior treatments . METHOD The authors examined the effects of clozapine , olanzapine , risperidone , and haloperidol on 16 measures of neurocognitive functioning in a double-blind , 14-week trial involving 101 patients . A global score was computed along with scores in four neurocognitive domains : memory , attention , motor function , and general executive and perceptual organization . RESULTS Global neurocognitive function improved with olanzapine and risperidone treatment , and these improvements were superior to those seen with haloperidol . Patients treated with olanzapine exhibited improvement in the general and attention domains but not more than that observed with other treatments . Patients treated with risperidone exhibited improvement in memory that was superior to that of both clozapine and haloperidol . Clozapine yielded improvement in motor function but not more than in other groups . Average effect sizes for change were in the small to medium range . More than half of the patients treated with olanzapine and risperidone experienced " clinical ly significant " improvement ( changes in score of at least one-half st and ard deviation relative to baseline ) . These findings did not appear to be mediated by changes in symptoms , side effects , or blood levels of medications . CONCLUSIONS Patients with a history of suboptimal response to conventional treatments may show cognitive benefits from newer antipsychotic drugs , and there may be differences between atypical antipsychotic drugs in their patterns of cognitive effects OBJECTIVE To investigate the neurocognitive effectiveness of haloperidol , risperidone , and olanzapine in first-episode schizophrenia-spectrum disorders . METHOD This prospect i ve , r and omized , open-label study was conducted from February 2001 to February 2005 . Data for the present investigation were obtained from a large epidemiologic and 3-year longitudinal intervention program of first-episode psychosis ( DSM-IV criteria ) conducted at the outpatient clinic and the inpatient unit at the University Hospital Marques de Valdecilla , Sant and er , Spain . One hundred four patients r and omly assigned to haloperidol ( N = 35 ) , olanzapine ( N = 30 ) , or risperidone ( N = 39 ) who completed clinical and cognitive evaluations at baseline , 6 months , and 1 year were included in the final analysis . Thirty-seven healthy individuals were also longitudinally assessed . A neuropsychological battery that comprised 9 cognitive domains was used . The contribution of clinical changes , concomitant medications , and the severity of motor side effects to cognitive changes was controlled . The main outcome measure was cognitive changes at 1-year follow-up . RESULTS The 3 treatment groups showed a significant improvement in cognitive scores after 1 year . The differential cognitive effectiveness between antipsychotics was insignificant . The magnitude of cognitive changes was similar in the 3 treatment groups and controls , although a greater improvement on the Finger Tapping Test , Trail Making Test B , and Rey Complex Figure Test was found in the treatment groups . Clinical changes , use of concomitant medications , and the emergence of motor side effects did not significantly account for cognitive changes over time . CONCLUSION Haloperidol , olanzapine , and risperidone were equally effective in treating cognitive deficits of psychosis . The effect of practice clearly contributes to cognitive score improvements after treatment with antipsychotics . Our results provide important information regarding the practical utility of antipsychotic treatments to improve cognition and could have implication s for developing novel approaches for cognitive pharmacotherapy in schizophrenia OBJECTIVE The authors sought to compare the effects of olanzapine , quetiapine , and risperidone on neurocognitive function in patients with early psychosis . METHOD In a 52-week double-blind , multicenter study , 400 patients early in the course of psychotic illness ( < 5 years ) were r and omly assigned to treatment with olanzapine ( 2.5 - 20 mg/day ) , quetiapine ( 100 - 800 mg/day ) , or risperidone ( 0.5 - 4 mg/day ) . The mean modal daily dose was 11.7 mg ( SD=5.3 ) for olanzapine , 506 mg ( SD=215 ) for quetiapine , and 2.4 mg ( SD=1.0 ) for risperidone . A total of 224 patients completed neurocognitive assessment s at baseline and at 12 weeks , and 81 patients also completed them at 52 weeks . Neurocognitive composite scores were calculated from the neurocognitive battery used in the Clinical Antipsychotic Trials of Intervention Effectiveness ( CATIE ) and from the Brief Assessment of Cognition in Schizophrenia . RESULTS At week 12 , there was significant improvement in neurocognition for each treatment ( p<0.01 ) , but no significant overall difference between treatments . Composite z score improvements on the CATIE neurocognitive battery were 0.17 for olanzapine , 0.33 for quetiapine , and 0.32 for risperidone .  Composite z score improvements on the Brief Assessment of Cognition in Schizophrenia were 0.19 for olanzapine , 0.34 for quetiapine , and 0.22 for risperidone . Statistically significant relationships between improvements in neurocognition and functional outcome were observed at weeks 12 and 52 . CONCLUSIONS Olanzapine , quetiapine , and risperidone all produced significant improvements in neurocognition in early-psychosis patients . Although cognitive improvements were modest , their clinical importance was suggested by relationships with improvements in functional outcome OBJECTIVE To compare the consequences of a guided discontinuation strategy and maintenance treatment in remitted first-episode psychosis in terms of relapse rates and functional outcome . METHOD The study was conducted in 7 mental health care organizations and the Department of Psychiatry of the University Medical Center Groningen in The Netherl and s , covering a catchment area of 3.1 million inhabitants . A sample of 131 remitted first-episode patients , aged 18 to 45 years , with a DSM-IV diagnosis of schizophrenia or related psychotic disorder was included ( i.e. , all patients with a first psychotic episode from October 2001 through December 2002 who were willing to participate ) . After 6 months of positive symptom remission , they were r and omly and openly assigned to the discontinuation strategy or maintenance treatment . Maintenance treatment was carried out according to American Psychiatric Association guidelines , preferably using low-dose atypical antipsychotics . The discontinuation strategy was carried out by gradual symptom-guided tapering of dosage and discontinuation if feasible . Follow-up was 18 months . Main outcome measures were relapse rates and social and vocational functioning . RESULTS Twice as many relapses occurred with the discontinuation strategy ( 43 % vs. 21 % , p = .011 ) . Of patients who received the strategy , approximately 20 % were successfully discontinued . Recurrent symptoms caused another approximately 30 % to restart antipsychotic treatment , while in the remaining patients discontinuation was not feasible at all . There were no advantages of the discontinuation strategy regarding functional outcome . CONCLUSIONS Only a limited number of patients can be successfully discontinued . High relapse rates do not allow a discontinuation strategy to be universal practice . However , if relapse risk can be carefully managed by close monitoring , in some remitted first-episode patients a guided discontinuation strategy may offer a feasible alternative to maintenance treatment 
    Output:
    
Antipsychotic treatment in patients with FEP produced high rates of remission in the year following treatment initiation , and untreated FEP reduced the odds of later achieving remission .
Maintenance therapy was more effective than treatment discontinuation or intermittent/guided discontinuation in preventing relapse .
Initiating antipsychotic treatment in patients with FEP also produced sustained cognitive improvement for up to 2 years .
CONCLUSION Treatment of patients with FEP is associated with benefits in the long-term outcomes of remission , relapse , and cognition .