***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: OBJECTIVE Despite the frequent use of the Positive and Negative Syndrome Scale ( PANSS ) for rating the symptoms of schizophrenia , the clinical meaning of its total score and of the cut-offs that are used to define treatment response ( e.g. at least 20 % or 50 % reduction of the baseline score ) are as yet unclear . We therefore compared the PANSS with simultaneous ratings of Clinical Global Impressions ( CGI ) . METHOD PANSS and CGI ratings at baseline ( n = 4091 ) , and after one , two , four and six weeks of treatment taken from a pooled data base of seven pivotal , multi-center antipsychotic drug trials on olanzapine or amisulpride in patients with exacerbations of schizophrenia were compared using equipercentile linking . RESULTS Being considered " mildly ill " according to the CGI approximately corresponded to a PANSS total score of 58 , " moderately ill " to a PANSS of 75 , " markedly ill " to a PANSS of 95 and severely ill to a PANSS of 116 . To be " minimally improved " according to the CGI score was associated with a mean percentage PANSS reduction of 19 % , 23 % , 26 % and 28 % at weeks 1 , 2 , 4 and 6 , respectively . The corresponding figures for a CGI rating " much improved " were 40 % , 45 % , 51 % and 53 % . CONCLUSIONS The results provide a better framework for underst and ing the clinical meaning of the PANSS total score in drug trials of schizophrenia patients with acute exacerbations . Such studies may ideally use at least a 50 % reduction from baseline cut-off to define response rather than lower thresholds . In treatment resistant population s , however , even a small improvement can be important , so that a 25 % cut-off might be appropriate The rationale for treating psychotic major depression with glucocorticoid receptor ( GR ) antagonists is review ed . Five patients with psychotic major depression were given 600 mg of mifepristone in a 4-day , double-blind , placebo-controlled crossover study . All the patients completed the protocol and adverse effects were not observed or reported . All of the five patients showed substantial improvements in their Hamilton Rating Scale for Depression scores while they were receiving mifepristone , and four of the five patients showed substantial improvement in their Brief Psychiatric Rating Scale scores . Little , if any , improvement was seen with placebo . These preliminary results suggest that short-term use of GR antagonists may be effective in the treatment of psychotic major depression and that additional study , perhaps using higher doses or more treatment days , seems warranted Summary : Background : Antiglucocorticoids , such as ketoconazole , have been investigated as antidepressant agents in major depression and other conditions . Despite evidence that a significant number of patients with schizophrenia and schizoaffective disorder are both hypercortisolemic and depressed , the antidepressant effects of antiglucocorticoids have never been assessed in these population s. Methods : Fifteen symptomatic patients with diagnoses of schizophrenia or schizoaffective disorder , who were at least partially treatment-resistant , were treated with ketoconazole , up to 800 mg/day , ( n = 8) or placebo ( n = 7 ) for four weeks in a double-blind manner . The study medication was added to a pre-stabilized antipsychotic and /or antidepressant medication regimen . Results : Ketoconazole treatment , compared to placebo , was associated with significant improvements in observer-rated depression , but not in subjectively rated depression , positive or negative psychotic symptom ratings , or cognitive performance scores . Conclusions : These pilot data partially support the hypothesis that antiglucocorticoids reduce depressive symptoms in patients with schizophrenia and schizoaffective disorder , although objective and subjective ratings may not be similarly affected during a four-week course of treatment . Further studies with larger sample sizes , more extensive endocrine assessment s and longer duration of drug administration seem warranted BACKGROUND Decreased hippocampal volume is observed in patients with Cushing 's syndrome and other conditions associated with elevated cortisol levels , stress , or both . Reversibility of hippocampal neuronal atrophy result ing from stress occurs in animals . Our study investigated the potential for reversibility of human hippocampal atrophy . METHODS The study included 22 patients with Cushing 's disease .  Magnetic resonance brain imaging was performed prior to transsphenoidal microadenomectomy and again after treatment . RESULTS Following treatment , hippocampal formation volume ( HFV ) increased by up to 10 % . The mean percent change ( 3.2 + /- 2.5 ) was significantly greater ( p < .04 ) than that of the comparison structure , cau date head volume ( 1.5 + /- 3.4 ) . Increase in HFV was significantly associated with magnitude of decrease in urinary free cortisol ( r = -.61 , p < .01 ) . This relationship strengthened after adjustments for age , duration of disease , and months elapsed since surgery ( r = -.70 , p < .001 ) . There was no significant correlation between cau date head volume change and magnitude of cortisol decrease . CONCLUSIONS Changes in human HFV associated with sustained hypercortisolemia are reversible , at least in part , once cortisol levels decrease . While many brain regions are likely affected by hypercortisolemia , the human hippocampus exhibits increased sensitivity to cortisol , affecting both volume loss and recovery Glucocorticoid ( GC ) exposure can affect brain function , including potential adverse effects on hippocampal physiology and on specific elements of cognitive performance . In a prior study of healthy adult humans , decreased verbal memory performance was detected during four days of double-blind , placebo-controlled dexamethasone ( DEX ) treatment . Using an identical experimental design and sample size ( n = 19 ) , the cognitive effect of DEX treatment was studied in 11 subjects with schizophrenia , compared with 8 receiving placebo .  In contrast to the effect in healthy adults , GC treatment with DEX at this dose ( cumulative 3.5 mg ) and duration did not decrease verbal memory performance or other measures of cognitive function in the patients with schizophrenia . When data from this experiment was compared with data from the previous study of healthy adults , covarying differences in baseline memory performance , a significant 3-way interaction was detected between subject group , treatment condition , and the repeated measurements of verbal memory performance across baseline , treatment and washout ( F[3,87 ] = 4.84 , p = .0066 ) , suggesting differential cognitive effects of DEX in the patients versus the previously studied healthy subjects . Baseline plasma cortisol concentrations ( 0800 h ) prior to DEX treatment were inversely correlated with baseline delayed ( rs = -0.536 , p = .03 ) verbal recall performance , supporting a previous report . The current results await replication using a larger sample size but provide preliminary evidence for an altered behavioral response to acute GC exposure in schizophrenic versus healthy subjects , and further evidence for a relationship between chronic changes in circulating cortisol and the memory impairments found in this disorder 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 The authors estimated components of variance and intraclass correlation coefficients ( ICCs ) to aid in the design of complex surveys and community intervention studies by analyzing data from the Health Survey for Engl and 1994 . This cross-sectional survey of English adults included data on a range of lifestyle risk factors and health outcomes . For the survey , households were sample d in 720 postal code sectors nested within 177 district health authorities and 14 regional health authorities . Study subjects were adults aged 16 years or more .  ICCs and components of variance were estimated from a nested r and om-effects analysis of variance . Results are presented at the district health authority , postal code sector , and household levels . Between-cluster variation was evident at each level of clustering . In these data , ICCs were inversely related to cluster size , but design effects could be substantial when the cluster size was large . Most ICCs were below 0.01 at the district health authority level , and they were mostly below 0.05 at the postal code sector level . At the household level , many ICCs were in the range of 0.0 - 0.3 . These data may provide useful information for the design of epidemiologic studies in which the units sample d or allocated range in size from households to large administrative areas CONTEXT Negative symptoms of schizophrenia are a prominent feature of the illness , and frequently remain refractory to treatment . Dehydroepi and rosterone ( DHEA ) , along with its sulfated form , DHEA-S , is an important circulating neurosteroid with several vital neurophysiological functions , including the regulation of neuronal excitability and function . OBJECTIVE Since the administration of DHEA has demonstrated improvement in mood , sense of well-being , interest , activity , and energy in several sub population s , we investigate the efficacy of DHEA in the management of the negative symptoms of schizophrenia . DESIGN Thirty DSM-IV-diagnosed schizophrenic patients with prominent negative symptoms ( in patients in a large referral state hospital ) were r and omized to receive either DHEA or placebo in double-blind fashion , in addition to regular antipsychotic medication , dose-stabilized prior to study entry . The DHEA was titrated up to a dose of 100 mg in divided doses during 6 weeks . RESULTS Results indicated significant improvement in negative symptoms ( P<.001 ) , as well as in depressive ( P<.05 ) and anxiety ( P<.001 ) symptoms in individuals receiving DHEA . This effect was especially noted in women . The improvement in negative symptoms was independent of improvement in depression . No differences were noted on the positive symptom subscale of the Positive and Negative Syndrome Scale ( PANSS ) or on the total PANSS score as compared with placebo . Subjects receiving DHEA demonstrated a significant increase in DHEA ( P<.05 ) and DHEA-S ( P<.01 ) plasma levels , without changes in cortisol levels . Increases in DHEA and plasma DHEA-S levels were correlated with improvement in negative symptoms ( P<.05 ) , but not with improvement in depressive and anxiety symptoms . No obvious adverse effects were experienced by participating subjects . CONCLUSIONS Our preliminary observations report for the first time in double-blind fashion the efficacy of DHEA augmentation in the management of negative , depressive , and anxiety symptoms of schizophrenia . The findings from this study raise important issues regarding the role of neurosteroids in general , and DHEA in particular , in the ongoing symptomatology and pharmacotherapy of schizophrenia Psychotic major depression ( PMD ) is found to be a relatively common psychiatric condition that affects up to nearly 20 % of patients with major depression . Previous studies by our group have shown rapid reversal of psychotic symptoms in some PMD patients treated with mifepristone , in addition to restoring a more normal afternoon cortisol release . The rationale for treating patients with PMD with a glucocorticosteroid receptor antagonist is further discussed . In total , 30 patients with PMD were treated with either 600 mg/day mifepristone or placebo for 8 days in a r and omized double-blind manner . The Hamilton Depression Rating Scale ( HDRS ) and the Brief Psychiatric Rating Scale ( BPRS ) were administered at baseline and again after 8 days of treatment . Cortisol and ACTH were measured hourly from 1800 to 0900 at baseline and after 8 days of treatment . Significantly , more patients in the mifepristone group ( seven of 15 ) showed a 50 % or greater decline on the BPRS positive symptom subscale , an 
    Output:
    
Data for main outcomes of interest were of low quality , and analysis of useable data showed no significant effects of treatment on mental state or adverse effects .
Good evidence is insufficient to conclude whether antiglucocorticoid drugs provide effective treatment for psychosis .
Some global state findings suggest a favourable effect for mifepristone  , and a few overall adverse effect findings favour placebo .