***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: R and omized controlled trials among patients with schizophrenia have shown that < 20 % improvement in the first two weeks of treatment predicts nonresponse after 12 weeks . The findings have been consistent for patients treated with both conventional ( 1 ) and second-generation antipsychotic ( AP ) drugs ( 2 ) . However , despite the lack of evidence regarding the length of time that clinicians should pursue one treatment regimen , most psychiatric textbooks and practice guidelines suggest that patients should be treated for at least four to six weeks with one AP ( 3 - 5 ) before switching to another ( 6 ) . Large pragmatic trials with chronic patients , such as the Clinical Antipsychotic Trials of Intervention Effectiveness ( CATIE ) ( 7 ) , have found no benefit from switching AP drugs ( 8,9 ) . No studies have considered less chronic patients , such as patients with recent-onset schizophrenia ( i.e. , less than five years of illness duration ) . We investigated responses to APs and switching strategies  in patients with recent-onset schizophrenia . We used the  IPAP  algorithm , which is a well-defined algorithm for treating schizophrenia ( 4,10 ) OBJECTIVE Clinical response to antipsychotic drug treatment is highly variable , yet prognostic biomarkers are lacking . The authors recently demonstrated that successful antipsychotic drug treatment alters resting-state functional connectivity of the striatum . The goal of the present study was to test whether intrinsic striatal connectivity patterns provide prognostic information and can serve as a potential biomarker of treatment response to antipsychotic drugs . METHOD The authors used resting-state functional MRI ( fMRI ) to develop a prognostic index in a discovery cohort of 41 first-episode schizophrenia patients , then tested this index in an independent cohort of 40 newly hospitalized chronic patients with acute psychosis . In the discovery cohort , patients underwent  resting-state fMRI scanning at the initiation of r and omized controlled treatment with a second-generation antipsychotic . Whole-brain functional connectivity maps were generated for each subject from striatal seed regions . A stringent measure of clinical response was calculated that required sustained improvement over two consecutive study visits . Clinical response was entered into a survival analysis , and Cox regression was applied to the functional connectivity data . A striatal connectivity index was created , comprising functional connections of the striatum that predicted treatment response . This striatal connectivity index was tested on a generalizability cohort of patients with psychotic disorders who were hospitalized for an acute psychotic episode . RESULTS A total of 91 regions functionally connected with the striatum provided significant prognostic information . Connectivity in these regions was used to create a baseline striatal connectivity index that predicted response to antipsychotic treatment with high sensitivity and specificity in both the discovery and generalizability cohorts . CONCLUSIONS These results provide evidence that individual differences in striatal functional connectivity predict response to antipsychotic drug treatment in acutely psychotic patients . With further development , this has the potential to serve as a prognostic biomarker with clinical utility and to reduce the overall burden associated with psychotic illnesses In the present study , including 66 schizophrenic patients and 73 healthy controls , the effect of atypical antipsychotic treatment over a period of 14 weeks on psychotic symptoms and plasma levels of glutamate and monoaminergic metabolites was investigated . Treatment induced a modest reduction of psychotic symptoms in 42 % of the patients ( response criterion : Brief Psychiatric Rating Scale [ BPRS ] decrease > /=40 % ) . Poor response was associated with severity of psychopathology , age and duration of disease . Glutamate at baseline was significantly higher in patients as compared to controls ( p<0.01 ) . During treatment , a significant further increase of glutamate , not related to response , was observed . Glutamate levels correlated significantly with negative symptom scores at baseline and weeks 3 , 6 and 14 ( p<0.05 ) . At baseline , serotonin ( 5-HT ) in plasma and 5-HT in platelets were significantly lower in the poor responders as compared to controls ( p<0.05 ) and increased significantly during treatment ( p<0.05 ) . In the responders , treatment coincided with a decrease of 5-HT parameters . No differences in plasma levels of HVA , 5-HIAA and their ratio were observed between controls and response groups . The results of this study suggest an effect of atypical antipsychotics on glutamatergic neurotransmission and an association between lower pretreatment peripheral 5-HT parameters and response Schizophrenia is a heterogeneous clinical condition that may reflect a variety of biological processes . In particular , treatment-resistant ( TR ) schizophrenia may have a distinct neurobiological substrate . Within the context of clinical data , a simultaneous study with different imaging techniques could help to eluci date differences in cerebral substrates among schizophrenia patients with different responses to treatment . In the present work we used a set of biological data ( basal and longitudinal volumetry , and P300 event-related potential measurements ) to compare TR and treatment-responsive chronic schizophrenia patients with healthy controls . The TR patients showed higher baseline clinical scores , a more severe basal profile of brain alterations , as well as a different outcome as regards to volume deficits . These data support the notion that biological substrates vary among groups of different psychotic patients , even when they have the same diagnosis , and that those substrates may be related to the response to treatment Connecticut State Hospital 's entire resident population ( n = 1,300 ) was screened on an arbitrary target day to determine eligibility for clozapine . Sixty percent of 803 patients with schizophrenia or schizoaffective disorder diagnoses met Food and Drug Administration ( FDA ) - approved criteria for clozapine use as judged by review of past medication trial records and by the responsible physicians . Eighty-eight percent of these patients were medically cleared , and of those cleared , 63 percent agreed to clozapine treatment . Of the patients who began a clozapine trial , 76 percent were still taking the drug 12 months later . Preliminary findings from a r and omized trial of clozapine versus usual care  ( n = 227 ) indicate that discharge rates associated with clozapine and usual care do not differ . Once discharged , however , patients assigned to clozapine are less likely to be readmitted . Hence , clozapine may be more cost-effective than usual care . However , before savings can be realized , State governments will have to make up-front investments of approximately $ 140 million simply to give patients hospitalized on a single day a year 's access to clozapine OBJECTIVE Early , effective treatment in first-episode schizophrenia is advocated , although evidence based on a systematic approach over multiple antipsychotic trials is lacking . Employing a naturalistic design , we examined response rates over 3 circumscribed antipsychotic trials . METHOD Between June 2003 and December 2008 , 244 individuals with first-episode schizophrenia or schizoaffective disorder according to DSM-IV criteria were treated at the Centre for Addiction and Mental Health , Toronto , Ontario , Canada , following an algorithm that moved them through 2 antipsychotic trials , followed by a trial with clozapine . For the first 2 trials , treatment consisted of risperidone followed by olanzapine , or vice versa ; each trial consisted of 3 stages ( low- , full- , or high-dose ) lasting up to 4 weeks at each level and adjusted according to response/tolerability . Clinical response was defined as a Clinical Global Impressions-Improvement score of 2 ( much improved ) or 1 ( very much improved ) and /or a Brief Psychiatric Rating Scale Thought Disorder subscale score ≤ 6 . Data were analyzed retrospectively , and publication of anonymized clinical data was approved by the Research Ethics Board of the Centre for Addiction and Mental Health in May 2003 . RESULTS In trial 1 , 74.5 % of individuals responded , with rates significantly higher for olanzapine ( 82.1 % , 115/140 ) versus risperidone ( 66.3 % , 69/104 ; P = .005 ) . With trial 2 , response rate dropped dramatically to 16.6 % but again was significantly higher for olanzapine ( 25.7 % , 9/35 ) compared to risperidone ( 4.0 % , 1/25 ; P = .04 ) . Response rate climbed above 70 % once more , specifically 75.0 % ( 21/28 ) , in those individuals who agreed to a third trial with clozapine . CONCLUSIONS Results confirm a high response rate ( 75 % ) to initial antipsychotic treatment in first-episode schizophrenia . A considerably lower response rate ( < 20 % ) occurs with a second antipsychotic trial . Results here were specific to olanzapine and risperidone , suggesting clinical differences ( ie , olanzapine more effective than risperidone ) . A subsequent trial with clozapine is clearly warranted , although it remains unclear whether outcome would be further enhanced if it were used earlier in the treatment algorithm The aim of this work was to compare achievements in milestones of community functioning in highly disabling psychiatric conditions , including treatment resistant schizophrenia ( TRS ) , schizophrenia ( responsive to antipsychotics ) , bipolar disorder , and anxiety/depressive diseases . Also , we investigated the predictors of community functioning outcomes across several domains . Among consecutive patients screened , 188 met inclusion criteria and 118 ultimately entered the study . Diagnosis of TRS was made by stringent criteria , including historic and perspective evaluations and excluding potential confounding factors . Achievements in functional milestones of everyday living were recorded . Performances in discrete cognitive tasks  were assessed . The Positive and Negative Syndrome Scale , the Personal and Social Performance Scale , the Drug Attitude Inventory-10 , and the Quality of Life Enjoyment and Satisfaction Question naire  were administered . TRS patients showed the highest impairment in community functioning among diagnostic groups . TRS was found to have more severe psychopathology , more impaired cognitive functioning , and poorer psychosocial adjustment compared to all the other groups . In the whole sample , the main predictors of community functioning were the diagnostic group ( with TRS diagnosis associated with worst functioning ) and achievements in the other functional milestones . In psychotic patients , however , the main predictors of community functioning were clinical and psychopathological variables . These results may support the hypothesis that TRS represents a separate schizophrenia subtype , with its own neurobiology , psychopathology and clinical course . Our results identify a group of modifiable predictors to be addressed to prevent community disability OBJECTIVE Clozapine is the only compound proven to be effective in the 20 % of schizophrenic patients refractory to treatment with conventional neuroleptics . Although its mechanism of action has not been eluci date d , clozapine appears , in contrast to most conventional neuroleptics , to be a potent serotonin ( 5-HT ) antagonist . This study hypothesized that 5-HT function is increased in patients who benefit from clozapine treatment relative to patients who fail to improve on it . METHOD The 5-HT receptor agonist m-chlorophenylpiperazine ( MCPP ) was used as a probe to examine 5-HT function . MCPP ( 0.35 mg/kg p.o . ) was administered in a placebo-controlled design after a 3-week drug-free period to 19 schizophrenic patients .  ACTH , prolactin , body temperature , behavior , and MCPP blood level were measured . Patients were then treated with a conventional neuroleptic , and , having failed to respond to it , were treated with clozapine for 5 weeks ( up to 600 mg/day ) . RESULTS Patients who responded to clozapine had significantly higher ACTH responses to MCPP during the drug-free state than the patients who failed to benefit from clozapine . Moreover , the degree of improvement with clozapine , particularly the improvement in psychotic symptoms , was strongly correlated with the magnitude of MCPP-induced ACTH release . Other MCPP-induced responses and MCPP blood level were similar for the two groups and did not correlate with the degree of symptomatic improvement with clozapine . CONCLUSIONS Results of this study suggest that MCPP-induced ACTH release , and by inference 5-HT receptor function , may be increased in patients who benefit from treatment with clozapine relative to patients who fail to improve on this drug D-fenfluramine has been identified as a highly selective serotonin ( 5-HT ) releaser and re-uptake inhibitor . The objective of our study was to investigate prolactin response to D-fenfluramine challenge in non-medicated , first episode schizophrenics . We hypothesized that 5-HT reactivity can predict a response to the neuroleptic treatment . Twenty-three in patients , 11 males and 12 females , at the Prague Psychiatric Center participated in the study . Inclusion criteria were : ICD-10 diagnosis of schizophrenia , first episode or duration of illness shorter than 36 months .  D-fenfluramine challenge test was performed before 4 weeks of the haloperidol treatment . During the test , prolactin plasma levels were measured . The Brief Psychiatric Rating Scale ( BPRS ) was administered before and after the treatment . A statistically significant negative correlation was found between prolactin response to the D-fenfluramine challenge and improvement of psychopathology measured by the change in total BPRS score ( p = 0.0004 ) , in positive ( p = 0.0403 ) , negative ( p = 0.0267 ) , and anxiety-depression symptoms of BPRS ( p = 0.0 
    Output:
    
The most robust findings indicate that treatment-resistant patients show glutamatergic abnormalities , a lack of dopaminergic abnormalities , and significant decreases in grey matter compared to treatment-responsive patients .
Conclusions Tentative evidence supports conceptualising treatment-resistant schizophrenia as a categorically different illness subtype to treatment-responsive schizophrenia .