human
***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 Vitamin B6 , or pyridoxine , plays an intrinsic role in the synthesis of certain neurotransmitters that take part in development of psychotic states . Several reports indicate that vitamin B6 may be a factor in a number of psychiatric disorders and related conditions , such as autism , Alzheimer 's disease , hyperactivity , learning disability , anxiety disorder , and depression . Moreover , there are anecdotal reports of a reduction in psychotic symptoms after vitamin B6 supplementation of psychopharmacologic treatment of patients suffering from schizophrenia or organic mental disorder . The aim of this study was to examine whether vitamin B6 therapy influences psychotic symptoms in patients suffering from schizophrenia and schizoaffective disorder . METHOD The effects of the supplementation of vitamin B6 to antipsychotic treatment on positive and negative symptoms in 15 schizophrenic and schizoaffective patients ( DSM-IV criteria ) were examined in a double-blind , placebo-controlled , crossover study spanning 9 weeks . All patients had stable psychopathology for at least 1 month before entry into the study and were maintained on treatment with their pre study  psychoactive and antiparkinsonian medications  throughout the study . All patients were assessed using the Positive and Negative Syndrome Scale ( PANSS ) for schizophrenia on a weekly basis . Patients r and omly received placebo or vitamin B6 , starting at 100 mg/day in the first week and increasing to 400 mg/day in the fourth week by 100-mg increments each week . RESULTS PANSS scores revealed no differences between vitamin B6- and placebo-treated patients in amelioration of their mental state . CONCLUSION Further studies with larger population s and shorter duration of illness are needed to clarify the question of the possible efficacy of vitamin B6 in treatment of psychotic symptoms in schizophrenia IMPORTANCE More effective treatments are needed for negative symptoms of schizophrenia , which are typically chronic , disabling , and costly . Negative symptoms have previously been associated with reduced blood folate levels , especially among patients with low-functioning variants in genes that regulate folate metabolism , suggesting the potential utility of folate supplementation . OBJECTIVES To determine whether folic acid plus vitamin B12 supplementation reduces negative symptoms of schizophrenia and whether functional variants in folate-related genes influence treatment response . DESIGN Parallel-group , r and omized , double-blind , placebo-controlled clinical trial of 16 weeks of treatment with 2 mg of folic acid and 400 μg of vitamin B12 . SETTING Three community mental health centers affiliated with academic medical centers in the United States . PARTICIPANTS Out patients with chronic schizophrenia who were psychiatrically stable but displayed persistent symptoms despite antipsychotic treatment . Eligible patients were 18 to 68 years old , were treated with an antipsychotic agent for 6 months or more at a stable dose for 6 weeks or more , and scored 60 or more on the Positive and Negative Syndrome Scale . INTERVENTION One hundred forty subjects were r and omized to receive daily oral folic acid plus vitamin B12 or placebo . MAIN OUTCOME MEASURES Change in negative symptoms ( Scale for the Assessment of Negative Symptoms [ SANS ] ) , as well as positive and total symptoms ( Positive and Negative Syndrome Scale ) . RESULTS Folate plus vitamin B12  improved negative symptoms significantly compared with placebo ( group difference , -0.33 change in SANS score per week ; 95 % CI , -0.62 to -0.05 ) when genotype was taken into account but not when genotype was excluded . An interaction of the 484C > T variant of FOLH1 ( rs202676 ) with treatment was observed ( P = .02 ) , where only patients homozygous for the 484 T allele demonstrated significantly greater benefit with active treatment ( -0.59 change in SANS score per week ; 95 % CI , -0.99 to -0.18 ) . In parallel , we observed an inverse relationship between red blood cell folate concentration at baseline and 484C allele load ( P = .03 ) , which persisted until 8 weeks of treatment . Change in positive and total symptoms did not differ between treatment groups . CONCLUSIONS Folate plus vitamin B12 supplementation can improve negative symptoms of schizophrenia , but treatment response is influenced by genetic variation in folate absorption . These findings support a personalized medicine approach for the treatment of negative symptoms . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00611806 OBJECTIVE Taurine is an inhibitory neuromodulatory amino acid in the central nervous system that activates the GABA- and glycine-insensitive chloride channel and inhibits the N-methyl-D-aspartate receptor . It also functions as a neuroprotective agent and has a role in neural development and neurogenesis . The aim of this study was to determine the efficacy of adjunctive taurine in improving symptomatology and cognition among patients with a DSM-IV first-episode psychotic disorder . METHODS 121 patients with first-episode psychosis , aged 18 - 25 years , attending early intervention services consented to participate in this r and omized , double-blind , placebo-controlled trial conducted from January 2007 to May 2009 . Patients taking low-dose antipsychotic medication were r and omly assigned to receive once-daily taurine 4 g or placebo for 12 weeks . The co primary outcomes were change in symptomatology ( measured by the Brief Psychiatric Rating Scale [ BPRS ] total score ) and change in cognition ( measured by the Measurement and Treatment Research to Improve Cognition in Schizophrenia [ MATRICS ] Consensus Cognitive Battery composite score ) at 12 weeks . Secondary outcomes included tolerability and safety and additional clinical and functioning measures . RESULTS 86 participants ( n = 47 taurine ; n = 39 placebo ) were included in the final analysis . Taurine significantly improved symptomatology measured by the BPRS total score ( 95 % CI , 1.8 - 8.5 ; P = .004 ) and psychotic subscale ( 95 % CI , 0.1 - 1.5 ; P = .026 ) compared to placebo . Additionally , improvements were observed in the Calgary Depression Scale for Schizophrenia ( 95 % CI , 0.1 - 3.0 ; P = .047 ) and Global Assessment of Functioning ( 95 % CI , 0.3 - 8.8 ; P = .04 ) scores . There was no group difference in composite cognitive score ( 95 % CI , -1.7 to 1.0 ; P = .582 ) . A significant group difference was found on one safety and tolerability item ( psychic item 2 , asthenia/lassitude/increased fatigability ) of the Udvalg for Kliniske Undersogelser , with the taurine group showing a more favorable outcome ( P = .006 ) . CONCLUSIONS Adjunctive taurine did not improve cognition , but it appears to improve psychopathology in patients with first-episode psychosis . The use of taurine warrants further investigation in larger r and omized studies , particularly early in the course of psychosis . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00420823 Background Supporting 21st century health care and the practice of evidence -based medicine ( EBM ) requires ubiquitous access to clinical information and to knowledge-based re sources to answer clinical questions . Many questions go unanswered , however , due to lack of skills in formulating questions , crafting effective search strategies , and accessing data bases to identify best levels of evidence . Methods This r and omized trial was design ed as a pilot study to measure the relevancy of search results using three different interfaces for the PubMed search system . Two of the search interfaces utilized a specific framework called PICO , which was design ed to focus clinical questions and to prompt for publication type or type of question asked . The third interface was the st and ard PubMed interface readily available on the Web . Study subjects were recruited from interns and residents on an inpatient general medicine rotation at an academic medical center in the US . Thirty-one subjects were r and omized to one of the three interfaces , given 3 clinical questions , and asked to search PubMed for a set of relevant articles that would provide an answer for each question . The success of the search results was determined by a precision score , which compared the number of relevant or gold st and ard articles retrieved in a result set to the total number of articles retrieved in that set . Results Participants using the PICO templates ( Protocol A or Protocol B ) had higher precision scores for each question than the participants who used Protocol C , the st and ard PubMed Web interface . ( Question 1 : A = 35 % , B = 28 % , C = 20 % ; Question 2 : A = 5 % , B = 6 % , C = 4 % ; Question 3 : A = 1 % , B = 0 % , C = 0 % ) 95 % confidence intervals were calculated for the precision for each question using a lower boundary of zero . However , the 95 % confidence limits were overlapping , suggesting no statistical difference between the groups . Conclusion Due to the small number of search es for each arm , this pilot study could not demonstrate a statistically significant difference between the search protocol s. However there was a trend towards higher precision that needs to be investigated in a larger study to determine if PICO can improve the relevancy of search results Background : Zinc can modulate fast-excitatory transmission , facilitate the release of amino butyric acid and potentiate nicotinic acetylcholine receptors . There are also emerging evidence s discussing the implication of these neurotransmitters in pathophysiology of schizophrenia . Objectives : The purpose of this study was to evaluate the efficacy of Zn sulfate as an add-on therapy in the treatment of schizophrenia in a 6-week , double-blind and placebo-controlled trial . Patients and Methods : Eligible participants were 30 in patients with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , Text Revision criteria . Patients were r and omly allocated into two equal groups ; one group of patients received risperidone 6 mg/day plus capsules of Zn sulfate ( each containing 50 mg elemental Zn ) three times a day and another group received risperidone 6 mg/day plus placebo . The Positive and Negative Syndrome Scale ( PANSS ) was applied to assess the psychotic symptoms and aggression risk at baseline , week 2 , 4 , and 6 of the study . Results : The results of this study showed that both protocol s significantly decreased the scores on all subscales of the PANSS and supplemental aggression risk subscale as well as PANSS total score over the study . However , this improvement was significantly higher in Zn sulfate receiving group compared to the placebo group . No major clinical side-effects were detected . Conclusions : It may be concluded that Zn is an effective adjuvant agent in the management of patients with schizophrenia Membrane lipid metabolism and redox regulation may be disturbed in schizophrenia . We examined the clinical effect of adding an omega-3 fatty acid and /or vitamins E+C to antipsychotics . It was hypothesized that lower baseline levels of polyunsaturated fatty acids ( PUFAs ) would predict more benefit from the add-on treatment . The trial had a multicenter , r and omized , double-blind , placebo-controlled 2 × 2 factorial design . Patients aged 18–39 years with schizophrenia or related psychoses were consecutively included at admission to psychiatric departments in Norway . They received active or placebo ethyl-eicosapentaenoate ( EPA ) 2 g day−1 and active or placebo vitamin E 364 mg day−1+vitamin C 1000 mg day−1 ( vitamins ) for 16 weeks . The main outcome measures were Positive and Negative Syndrome Scale ( PANSS ) total and subscales scores , analyzed by linear mixed models . Ninety-nine patients were included . At baseline , erythrocyte PUFA were measured in 97 subjects . Given separately , EPA and vitamins  increased drop-out rates , whereas when combined they did not differ from placebo . In low PUFA patients , EPA alone impaired the course of total PANSS ( Cohen ’s d=0.29 ; P=0.03 ) and psychotic symptoms ( d=0.40 ; P=0.003 ) , especially persecutory delusions ( d=0.48 ; P=0.0004 ) . Vitamins alone impaired the course of psychotic symptoms ( d= 0.37 ; P=0.005 ) , especially persecutory delusions ( d=0.47 ; P=0.0005 ) . Adding vitamins to EPA neutralized the detrimental effect on psychosis ( interaction d=0.31 ; P=0.02 ) . In high PUFA patients , there were no significant effects of trial drugs on PANSS scales . In conclusion , given separately during an acute episode , EPA and vitamins E+C  induce psychotic symptoms in patients with low levels of PUFA . Combined , these agents seem safe Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more BACKGROUND Brain glutathione levels are decreased in schizophrenia , a disorder that often is chronic and refract 
    Output:
    
agent
There were no overall effects from antioxidant vitamins , inositol or dietary minerals on psychiatric symptoms .
There is preliminary evidence that certain vitamin and mineral supplements may reduce psychiatric symptoms in some people with schizophrenia .
***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 Vitamin B6 , or pyridoxine , plays an intrinsic role in the synthesis of certain neurotransmitters that take part in development of psychotic states . Several reports indicate that vitamin B6 may be a factor in a number of psychiatric disorders and related conditions , such as autism , Alzheimer 's disease , hyperactivity , learning disability , anxiety disorder , and depression . Moreover , there are anecdotal reports of a reduction in psychotic symptoms after vitamin B6 supplementation of psychopharmacologic treatment of patients suffering from schizophrenia or organic mental disorder . The aim of this study was to examine whether vitamin B6 therapy influences psychotic symptoms in patients suffering from schizophrenia and schizoaffective disorder . METHOD The effects of the supplementation of vitamin B6 to antipsychotic treatment on positive and negative symptoms in 15 schizophrenic and schizoaffective patients ( DSM-IV criteria ) were examined in a double-blind , placebo-controlled , crossover study spanning 9 weeks . All patients had stable psychopathology for at least 1 month before entry into the study and were maintained on treatment with their pre study  psychoactive and antiparkinsonian medications  throughout the study . All patients were assessed using the Positive and Negative Syndrome Scale ( PANSS ) for schizophrenia on a weekly basis . Patients r and omly received placebo or vitamin B6 , starting at 100 mg/day in the first week and increasing to 400 mg/day in the fourth week by 100-mg increments each week . RESULTS PANSS scores revealed no differences between vitamin B6- and placebo-treated patients in amelioration of their mental state . CONCLUSION Further studies with larger population s and shorter duration of illness are needed to clarify the question of the possible efficacy of vitamin B6 in treatment of psychotic symptoms in schizophrenia IMPORTANCE More effective treatments are needed for negative symptoms of schizophrenia , which are typically chronic , disabling , and costly . Negative symptoms have previously been associated with reduced blood folate levels , especially among patients with low-functioning variants in genes that regulate folate metabolism , suggesting the potential utility of folate supplementation . OBJECTIVES To determine whether folic acid plus vitamin B12 supplementation reduces negative symptoms of schizophrenia and whether functional variants in folate-related genes influence treatment response . DESIGN Parallel-group , r and omized , double-blind , placebo-controlled clinical trial of 16 weeks of treatment with 2 mg of folic acid and 400 μg of vitamin B12 . SETTING Three community mental health centers affiliated with academic medical centers in the United States . PARTICIPANTS Out patients with chronic schizophrenia who were psychiatrically stable but displayed persistent symptoms despite antipsychotic treatment . Eligible patients were 18 to 68 years old , were treated with an antipsychotic agent for 6 months or more at a stable dose for 6 weeks or more , and scored 60 or more on the Positive and Negative Syndrome Scale . INTERVENTION One hundred forty subjects were r and omized to receive daily oral folic acid plus vitamin B12 or placebo . MAIN OUTCOME MEASURES Change in negative symptoms ( Scale for the Assessment of Negative Symptoms [ SANS ] ) , as well as positive and total symptoms ( Positive and Negative Syndrome Scale ) . RESULTS Folate plus vitamin B12  improved negative symptoms significantly compared with placebo ( group difference , -0.33 change in SANS score per week ; 95 % CI , -0.62 to -0.05 ) when genotype was taken into account but not when genotype was excluded . An interaction of the 484C > T variant of FOLH1 ( rs202676 ) with treatment was observed ( P = .02 ) , where only patients homozygous for the 484 T allele demonstrated significantly greater benefit with active treatment ( -0.59 change in SANS score per week ; 95 % CI , -0.99 to -0.18 ) . In parallel , we observed an inverse relationship between red blood cell folate concentration at baseline and 484C allele load ( P = .03 ) , which persisted until 8 weeks of treatment . Change in positive and total symptoms did not differ between treatment groups . CONCLUSIONS Folate plus vitamin B12 supplementation can improve negative symptoms of schizophrenia , but treatment response is influenced by genetic variation in folate absorption . These findings support a personalized medicine approach for the treatment of negative symptoms . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00611806 OBJECTIVE Taurine is an inhibitory neuromodulatory amino acid in the central nervous system that activates the GABA- and glycine-insensitive chloride channel and inhibits the N-methyl-D-aspartate receptor . It also functions as a neuroprotective agent and has a role in neural development and neurogenesis . The aim of this study was to determine the efficacy of adjunctive taurine in improving symptomatology and cognition among patients with a DSM-IV first-episode psychotic disorder . METHODS 121 patients with first-episode psychosis , aged 18 - 25 years , attending early intervention services consented to participate in this r and omized , double-blind , placebo-controlled trial conducted from January 2007 to May 2009 . Patients taking low-dose antipsychotic medication were r and omly assigned to receive once-daily taurine 4 g or placebo for 12 weeks . The co primary outcomes were change in symptomatology ( measured by the Brief Psychiatric Rating Scale [ BPRS ] total score ) and change in cognition ( measured by the Measurement and Treatment Research to Improve Cognition in Schizophrenia [ MATRICS ] Consensus Cognitive Battery composite score ) at 12 weeks . Secondary outcomes included tolerability and safety and additional clinical and functioning measures . RESULTS 86 participants ( n = 47 taurine ; n = 39 placebo ) were included in the final analysis . Taurine significantly improved symptomatology measured by the BPRS total score ( 95 % CI , 1.8 - 8.5 ; P = .004 ) and psychotic subscale ( 95 % CI , 0.1 - 1.5 ; P = .026 ) compared to placebo . Additionally , improvements were observed in the Calgary Depression Scale for Schizophrenia ( 95 % CI , 0.1 - 3.0 ; P = .047 ) and Global Assessment of Functioning ( 95 % CI , 0.3 - 8.8 ; P = .04 ) scores . There was no group difference in composite cognitive score ( 95 % CI , -1.7 to 1.0 ; P = .582 ) . A significant group difference was found on one safety and tolerability item ( psychic item 2 , asthenia/lassitude/increased fatigability ) of the Udvalg for Kliniske Undersogelser , with the taurine group showing a more favorable outcome ( P = .006 ) . CONCLUSIONS Adjunctive taurine did not improve cognition , but it appears to improve psychopathology in patients with first-episode psychosis . The use of taurine warrants further investigation in larger r and omized studies , particularly early in the course of psychosis . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT00420823 Background Supporting 21st century health care and the practice of evidence -based medicine ( EBM ) requires ubiquitous access to clinical information and to knowledge-based re sources to answer clinical questions . Many questions go unanswered , however , due to lack of skills in formulating questions , crafting effective search strategies , and accessing data bases to identify best levels of evidence . Methods This r and omized trial was design ed as a pilot study to measure the relevancy of search results using three different interfaces for the PubMed search system . Two of the search interfaces utilized a specific framework called PICO , which was design ed to focus clinical questions and to prompt for publication type or type of question asked . The third interface was the st and ard PubMed interface readily available on the Web . Study subjects were recruited from interns and residents on an inpatient general medicine rotation at an academic medical center in the US . Thirty-one subjects were r and omized to one of the three interfaces , given 3 clinical questions , and asked to search PubMed for a set of relevant articles that would provide an answer for each question . The success of the search results was determined by a precision score , which compared the number of relevant or gold st and ard articles retrieved in a result set to the total number of articles retrieved in that set . Results Participants using the PICO templates ( Protocol A or Protocol B ) had higher precision scores for each question than the participants who used Protocol C , the st and ard PubMed Web interface . ( Question 1 : A = 35 % , B = 28 % , C = 20 % ; Question 2 : A = 5 % , B = 6 % , C = 4 % ; Question 3 : A = 1 % , B = 0 % , C = 0 % ) 95 % confidence intervals were calculated for the precision for each question using a lower boundary of zero . However , the 95 % confidence limits were overlapping , suggesting no statistical difference between the groups . Conclusion Due to the small number of search es for each arm , this pilot study could not demonstrate a statistically significant difference between the search protocol s. However there was a trend towards higher precision that needs to be investigated in a larger study to determine if PICO can improve the relevancy of search results Background : Zinc can modulate fast-excitatory transmission , facilitate the release of amino butyric acid and potentiate nicotinic acetylcholine receptors . There are also emerging evidence s discussing the implication of these neurotransmitters in pathophysiology of schizophrenia . Objectives : The purpose of this study was to evaluate the efficacy of Zn sulfate as an add-on therapy in the treatment of schizophrenia in a 6-week , double-blind and placebo-controlled trial . Patients and Methods : Eligible participants were 30 in patients with schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition , Text Revision criteria . Patients were r and omly allocated into two equal groups ; one group of patients received risperidone 6 mg/day plus capsules of Zn sulfate ( each containing 50 mg elemental Zn ) three times a day and another group received risperidone 6 mg/day plus placebo . The Positive and Negative Syndrome Scale ( PANSS ) was applied to assess the psychotic symptoms and aggression risk at baseline , week 2 , 4 , and 6 of the study . Results : The results of this study showed that both protocol s significantly decreased the scores on all subscales of the PANSS and supplemental aggression risk subscale as well as PANSS total score over the study . However , this improvement was significantly higher in Zn sulfate receiving group compared to the placebo group . No major clinical side-effects were detected . Conclusions : It may be concluded that Zn is an effective adjuvant agent in the management of patients with schizophrenia Membrane lipid metabolism and redox regulation may be disturbed in schizophrenia . We examined the clinical effect of adding an omega-3 fatty acid and /or vitamins E+C to antipsychotics . It was hypothesized that lower baseline levels of polyunsaturated fatty acids ( PUFAs ) would predict more benefit from the add-on treatment . The trial had a multicenter , r and omized , double-blind , placebo-controlled 2 × 2 factorial design . Patients aged 18–39 years with schizophrenia or related psychoses were consecutively included at admission to psychiatric departments in Norway . They received active or placebo ethyl-eicosapentaenoate ( EPA ) 2 g day−1 and active or placebo vitamin E 364 mg day−1+vitamin C 1000 mg day−1 ( vitamins ) for 16 weeks . The main outcome measures were Positive and Negative Syndrome Scale ( PANSS ) total and subscales scores , analyzed by linear mixed models . Ninety-nine patients were included . At baseline , erythrocyte PUFA were measured in 97 subjects . Given separately , EPA and vitamins  increased drop-out rates , whereas when combined they did not differ from placebo . In low PUFA patients , EPA alone impaired the course of total PANSS ( Cohen ’s d=0.29 ; P=0.03 ) and psychotic symptoms ( d=0.40 ; P=0.003 ) , especially persecutory delusions ( d=0.48 ; P=0.0004 ) . Vitamins alone impaired the course of psychotic symptoms ( d= 0.37 ; P=0.005 ) , especially persecutory delusions ( d=0.47 ; P=0.0005 ) . Adding vitamins to EPA neutralized the detrimental effect on psychosis ( interaction d=0.31 ; P=0.02 ) . In high PUFA patients , there were no significant effects of trial drugs on PANSS scales . In conclusion , given separately during an acute episode , EPA and vitamins E+C  induce psychotic symptoms in patients with low levels of PUFA . Combined , these agents seem safe Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more BACKGROUND Brain glutathione levels are decreased in schizophrenia , a disorder that often is chronic and refract 
    Output:
    