***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: Publication bias , sometimes known as the " file-drawer problem " or " funnel-plot asymmetry , " is common in empirical research . The authors review the implication s of publication bias for quantitative research synthesis ( meta- analysis ) and describe existing techniques for detecting and correcting it . A new approach is proposed that is suitable for application to meta-analytic data sets that are too small for the application of existing methods . The model estimates parameters relevant to fixed-effects , mixed-effects or r and om-effects meta- analysis contingent on a hypothetical pattern of bias that is fixed independently of the data . The authors illustrate this approach for sensitivity analysis using 3 data sets adapted from a commonly cited reference work on research synthesis ( H. M. Cooper & L. V. Hedges , 1994 ) Impairments of attention and memory are evident in early psychosis , and are associated with functional disability . In a group of stable , medicated women patients , we aim ed to determine whether participating in aerobic exercise or yoga improved cognitive impairments and clinical symptoms . A total of 140 female patients were recruited , and 124 received the allocated intervention in a r and omized controlled study of 12 weeks of yoga or aerobic exercise compared with a waitlist group . The primary outcomes were cognitive functions including memory and attention . Secondary outcome measures were the severity of psychotic and depressive symptoms , and hippocampal volume . Data from 124 patients were included in the final analysis based on the intention-to-treat principle . Both yoga and aerobic exercise groups demonstrated significant improvements in working memory ( P<0.01 ) with moderate to large effect sizes compared with the waitlist control group . The yoga group showed additional benefits in verbal acquisition ( P<0.01 ) and attention ( P=0.01 ) . Both types of exercise improved overall and depressive symptoms ( all P⩽0.01 ) after 12 weeks . Small increases in hippocampal volume were observed in the aerobic exercise group compared with waitlist ( P=0.01 ) . Both types of exercise improved working memory in early psychosis patients , with yoga having a larger effect on verbal acquisition and attention than aerobic exercise . The application of yoga and aerobic exercise as adjunctive treatments for early psychosis merits serious consideration . This study was supported by the Small Research Funding of the University of Hong Kong ( 201007176229 ) , and RGC funding ( C00240/762412 ) by the Authority of Research , Hong Kong 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 Varenicline , alpha4beta2 nicotinic acetylcholine receptor ( nAChR ) partial agonist , is a new class of medications for treating nicotine dependence . As an alpha4beta2 nAChR partial agonist , varenicline serves to reduce nicotine withdrawal symptoms , while high-affinity binding of the agonist mitigates the reinforcing effects of smoking . In the present study , we compared serum brain-derived neurotrophic factor ( BDNF ) levels of nicotine dependence and nonsmokers , and we investigated changes in serum BDNF levels after 8 weeks of treatment with varenicline .  Patients met the DSM-IV criteria for nicotine dependence . Both the Fagerström test for nicotine dependence ( FTND ) and the Tobacco Dependence Screener ( TDS ) were used . Serum BDNF levels and breath carbon monoxide ( CO ) levels were measured before and 8 weeks after varenicline treatment . Fourteen of 16 subjects ( 87.5 % ) stopped smoking within 12 weeks of varenicline treatment . Thirteen healthy nonsmokers who never had previously smoked were r and omly selected as a control group .  Serum BDNF levels of patients before treatment ( 4.8 + /- 3.8 ng/ml ) were significantly lower than those in the control group ( 12.4 + /- 6.13 ng/ml ) . Serum BDNF levels had not increased from baseline ( 4.8 + /- 3.8 ng/ml ) to 8 weeks after varenicline treatment ( 3.0 + /- 1.1 ng/ml ) of patients . These results suggest that smoking might decrease serum BDNF levels and that treatment with varenicline for 8 weeks , combined with 12 weeks of not smoking , does not increase serum BDNF levels in smokers OBJECTIVE To examine the effects of Hatha yoga therapy on resilience , brain-derived neurotrophic factor ( BDNF ) levels , and salivary alpha amylase ( SAA ) activity in patients with schizophrenia-spectrum disorders . DESIGN AND PARTICIPANTS Single-blinded , r and omized controlled study in which out patients with schizophrenia or related psychotic disorders ( according to International Classification of Diseases , 10th Revision ) were r and omly assigned to a yoga or a control group . SETTING November 2012-April 2013 at Yamanashi Prefectural Kita Hospital , Japan . INTERVENTIONS In the yoga group , patients received weekly 1-hour Hatha yoga sessions , in addition to regular treatment , for 8 weeks . Those in the control group underwent regular treatment , which included a daycare rehabilitation program . OUTCOME MEASURES Assessment s included the 25-item Resilience Scale ( RS ) , Positive and Negative Syndrome Scale ( PANSS ) , plasma and salivary BDNF level , and SAA activity . RESULTS Fifty patients participated ( 25 in each group ; mean age±st and ard deviation , 50.9±11.3 years ; mean duration of illness , 25.0±10.3 years ; mean total PANSS score , 78.2±17.3 ) . No significant differences in changes in any variable from baseline to week 8 were found between the two groups ( changes in the yoga group versus the control group : RS score , -1.6±19.9 versus 0.3±17.2 ; PANSS score , 0.5±12.0 versus 5.0±15.6 ; plasma BDNF , 41.6±377.0 pg/dl versus 73.4±346.0 pg/dl ; SAA , -26.2±72.6 kU/l versus -13.8±68.0 kU/l , respectively ) . CONCLUSIONS Adjunct yoga therapy showed no positive changes in resilience level or stress markers . Duration and intensity of yoga sessions and the focus on patients with chronic illness may explain the negative observations in light of past positive evidence regarding yoga therapy 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 Objectives : l-Theanine ( & ggr;-glutamylethylamide ) augmentation to antipsychotic therapy ameliorates positive , activation , and anxiety symptoms in schizophrenia and schizoaffective disorder patients . This study examines the association between circulating levels of neurochemical indicators and the beneficial clinical effects of l-theanine augmentation . Methods : Serum levels of neurochemical indicators such as brain-derived neurotrophic factor ( BDNF ) , dehydroepi and rosterone ( DHEA ) , its sulfate ( DHEAS ) , cortisol , cholesterol , and insulin were monitored in 40 schizophrenia and schizoaffective disorder patients during an 8-week , double-blind , r and omized , placebo-controlled trial with l-theanine ( 400 mg/d ) . Multiple regression analysis was applied for search ing association between improvement in symptom scores and changes in circulating levels of neurochemical indicators for an 8-week trial . Results : Regression models among l-theanine-treated patients indicate that circulating levels of BDNF and cortisol-to-DHEAS*100 molar ratio were significantly associated with the beneficial clinical effects of l-theanine augmentation . Variability of serum BDNF levels accounted for 26.2 % of the total variance in reduction of dysphoric mood and 38.2 % in anxiety scores . In addition , the changes in cortisol-to-DHEAS*100 molar ratio accounted for 30 % to 34 % of the variance in activation factor and dysphoric mood scores and for 15.9 % in anxiety scores . Regression models among placebo-treated patients did not reach significant level . Conclusions : These preliminary results indicate that circulating BDNF and cortisol-to-DHEAS*100 molar ratio may be involved in the beneficial clinical effects of l-theanine as augmentation of antipsychotic therapy in schizophrenia and schizoaffective disorder patients There is evidence that major psychiatric discords such as schizophrenia ( SZ ) and bipolar disorder ( BD ) are associated with dysregulation of synaptic plasticity with downstream alterations of neurotrophins . Brain-derived neurotrophic factor ( BDNF ) is the most widely distributed neurotrophin in the central nervous system ( CNS ) , and performs many biological functions such as promoting the survival , differentiation , and plasticity of neurons . Variants in the BDNF gene increase the risk of SZ and bipolar disorder . Chronic administration of drugs used to treat SZ and BD , such as lithium , valproate , quetiapine , clozapine , and olanzapine , increases BDNF expression in rat brain . To examine serum BDNF , three groups of chronically medicated DSM-IV SZ patients , on treatment with clozapine ( n=27 ) , typical ( n=14 ) , and other atypical antipsychotics ( n=19 ) , 30 euthymic BD patients , and 26 healthy control had 5 ml blood sample s collected by venipuncture . Serum BDNF levels were significantly higher in SZ patients ( p<0.001 ) when compared to either controls or euthymic BD patients . Increased BDNF in SZ patients might be related to the course of illness or to treatment variables . Prospect i ve studies are warranted Some pre clinical and postmortem studies suggest that the effects of atypical antipsychotics could be mediated by brain-derived neurotrophic factor ( BDNF ) . Olanzapine is an atypical antipsychotic with shown efficacy in psychosis treatment . The aim of this study was to compare plasma BDNF levels at baseline and after 1 year of olanzapine treatment in 18 drug-naive patients who experienced a first psychotic episode with those of 18 healthy control participants matched by age , sex , and socioeconomic level .  Plasma BDNF levels were measured in patients at the index episode and at 1 , 6 , and 12 months of follow-up using an enzyme-linked immunosorbent assay . Symptoms and functioning of patients and controls were assessed with the Positive and Negative Symptom Scale and Global Assessment of Function Scale . BDNF levels of patients at on 
    Output:
    
Despite insufficient evidence to draw a conclusion , our results suggest that use of NPIs as adjunctive treatments , specifically non-exercise interventions , may affect positively serum or plasma BDNF in patients with schizophrenia