***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: Our previous work has identified that unmedicated volunteers with schizophrenia have regional cerebral blood flow ( rCBF ) activation patterns inappropriately related to the cognitive dem and of a task in anterior cingulate cortex ( ACC ) . Using positron emission tomography ( PET ) with 15O water , we compared task-induced rCBF patterns induced by haloperidol or clozapine in individuals with schizophrenia . We hypothesized that clozapine , given its superior clinical action , would tend to normalize the abnormal task-activated response in ACC more than haloperidol . Schizophrenia volunteers ( SVs ) ( n=6 ) and normal volunteers ( NVs ) ( n=12 ) were trained to perform a tone discrimination task with 70–80 % accuracy . They were then scanned during three task conditions : ( 1 ) Rest , ( 2 ) sensory motor control ( SMC ) task , and ( 3 ) decision task ( DEC ) . SVs were initially scanned after withdrawal of all psychotropic medication and again after treatment with therapeutic doses of haloperidol ( n=5 ) and /or clozapine ( n=5 ) . rCBF values , sample d in the grown maxima of the task-activated ACC cluster , were analyzed between groups and task conditions . Task performance was similar across the unmedicated ,  haloperidol- and clozapine-medicated  SV groups . There was a reduction in accuracy in the haloperidol SV group compared to the NVs . Group and task conditions affected rCBF in the ACC . Clozapine , but not haloperidol , reversed the abnormal ACC rCBF pattern in unmedicated SV to normal . The clozapine-treated SV group showed a rCBF pattern similar to the NV group in that ACC activation was not observed during the control task but occurred during the decision condition . The pattern seen in the haloperidol-treated SV group was similar to the unmedicated SV group in that ACC activation was seen during the control task and no further activation was seen during the DEC . We report that clozapine , but not haloperidol , normalizes anterior cingulate rCBF patterns in schizophrenia during a cognitive task . Based on these preliminary data , we propose that this pattern may account for the superior therapeutic effect of clozapine and represents a surrogate marker of this action OBJECTIVE Studies have found that cau date volume increased after treatment with typical antipsychotics in patients with schizophrenia but decreased after treatment was changed to clozapine . In the current study the authors examined whether this volume decrease was related to clinical improvement . METHOD Twenty-eight patients with schizophrenia who had not responded to treatment with typical antipsychotics were included in the study ; 22 completed the study .  Cau date volume was assessed by using magnetic resonance imaging during treatment with typical antipsychotics and after 24 weeks and 52 weeks of clozapine treatment . Symptoms were assessed just before clozapine treatment and once a month thereafter . RESULTS Clozapine treatment result ed in a significant reduction in left cau date volume in patients who responded to the drug but not in patients who did not respond to clozapine at 52 weeks of treatment . Overall , the degree of reduction in left cau date volume was significantly related to the extent of improvement in positive and general symptoms but not in negative symptoms . CONCLUSIONS These findings suggest that the cau date nucleus plays a role in the positive and general symptoms of schizophrenia BACKGROUND Pathomorphologic brain changes occurring as early as first-episode schizophrenia have been extensively described . Longitudinal studies have demonstrated that these changes may be progressive and associated with clinical outcome . This raises the possibility that antipsychotics might alter such pathomorphologic progression in early-stage schizophrenia . OBJECTIVE To test a priori hypotheses that olanzapine-treated patients have less change over time in whole brain gray matter volumes and lateral ventricle volumes than haloperidol-treated patients and that gray matter and lateral ventricle volume changes are associated with changes in psychopathology and neurocognition . DESIGN Longitudinal , r and omized , controlled , multisite , double-blind study . Patients treated and followed up for up to 104 weeks .  Neurocognitive and magnetic resonance imaging ( MRI ) assessment  s performed at weeks 0 ( baseline ) , 12 , 24 , 52 , and 104 . Mixed-models analyses with time-dependent covariates evaluated treatment effects on MRI end points and explored relationships between MRI , psychopathologic , and neurocognitive outcomes . SETTING Fourteen academic medical centers ( United States , 11 ; Canada , 1 ; Netherl and s , 1 ; Engl and , 1 ) . PARTICIPANTS Patients with first-episode psychosis ( DSM-IV ) and healthy volunteers . INTERVENTIONS R and om allocation to a conventional antipsychotic , haloperidol ( 2 - 20 mg/d ) , or an atypical antipsychotic , olanzapine ( 5 - 20 mg/d ) . MAIN OUTCOME MEASURES Brain volume changes assessed by MRI . RESULTS Of 263 r and omized patients , 161 had baseline and at least 1 postbaseline MRI evaluation .  Haloperidol-treated patients exhibited significant decreases in gray matter volume , whereas olanzapine-treated patients did not . A matched sample of healthy volunteers ( n = 58 ) examined contemporaneously showed no change in gray matter volume . CONCLUSIONS Patients with first-episode psychosis exhibited a significant between-treatment difference in MRI volume changes .  Haloperidol was associated with significant reductions in gray matter volume , whereas olanzapine was not . Post hoc analyses suggested that treatment effects on brain volume and psychopathology of schizophrenia may be associated . The differential treatment effects on brain morphology could be due to haloperidol-associated toxicity or greater therapeutic effects of olanzapine BACKGROUND Little is known about the effects of antipsychotic medications on gray matter ( GM ) in schizophrenia . Although clozapine remains the most effective antipsychotic medication in treatment-refractory cases , it is unknown whether it has a differential effect on GM development . METHODS In an exploratory analysis , we used automated cortical thickness measurements and prospect ively scanned childhood-onset schizophrenia ( COS ) patients who were maintained on one medication . Two atypical antipsychotic medications , clozapine ( n=12 , 37 scans ) and olanzapine ( n=12 , 33 scans ) were compared with respect to effects on cortical development , in contrast to GM trajectories of matched controls . RESULTS There were no significant differences in the trajectories of cortical thickness between the two treatment groups with the exception of a small circumscribed area in the right prefrontal cortex , where the olanzapine group showed thicker cortex . As expected , both groups showed thinner GM compared to matched controls . CONCLUSIONS Although these analyses do not rule out effects of antipsychotic medications on GM development in schizophrenia , they show no differential effect between clozapine and olanzapine on GM trajectory Subtraction ictal single photon emission tomography ( SPET ) co-registered to magnetic resonance imaging ( SISCOM ) is an ictal-interictal brain perfusion SPET subtraction method , developed for evaluation of brain perfusion changes applied for the identification of epileptic foci . The aim of this study was to test whether regional cerebral blood flow ( rCBF ) alterations due to clozapine in schizophrenic patients could also be detected with SISCOM . We have studied the brain perfusion SPET data  obtained both before ( pre-SPET ) and 8 weeks after ( post-SPET ) clozapine treatment , in 20 patients with schizophrenia . These data were used for SISCOM processing . In order to identify any alterations in the perfusion pattern using SISCOM , pre- and post-SPET data were subtracted from each other . Activation maps were created and merged on either pre- or post-SPET images . Visual interpretation of brain perfusion SPET studies were performed and compared with SISCOM findings . We found that final SISCOM images and visual evaluation of pre- and post-SPET studies were well concordant in 17/20 patients . Discordance was observed in 3 patients . In 1 of these 3 patients alterations observed with SISCOM were confirmed as subtle changes on visual re-evaluation of the images . In the remaining 2 of these 3 patients , SISCOM did not confirm the changes observed by visual analysis . Additionally , SISCOM depicted perfusion alteration in occipital cortex in 5 patients . In conclusion , the algorithm of SISCOM seemed to be useful and complementary to visual evaluation , to assess rCBF changes due to clopazine in outpatient schizophrenic patients who had treatment refractoriness or intolerance of previous antipsychotics and to provide additional information when both pre- and post-SPET data were subtracted from each other BACKGROUND Approximately 50 % of patients with schizophrenia or schizoaffective disorder attempt suicide , and approximately 10 % die of suicide . Study results suggest that clozapine therapy significantly reduces suicidal behavior in these patients . METHODS A multicenter , r and omized , international , 2-year study comparing the risk for suicidal behavior in patients treated with clozapine vs olanzapine was conducted in 980 patients with schizophrenia or schizoaffective disorder , 26.8 % of whom were refractory to previous treatment , who were considered at high risk for suicide because of previous suicide attempts or current suicidal ideation . To equalize clinical contact across treatments , all patients were seen weekly for 6 months and then biweekly for 18 months . Subsequent to r and omization , unmasked clinicians at each site could make any interventions necessary to prevent the occurrence of suicide attempts . Suicidal behavior was assessed at each visit . Primary end points included suicide attempts ( including those that led to death ) , hospitalizations to prevent suicide , and a rating of " much worsening of suicidality " from baseline . Masked raters , including an independent suicide monitoring board , determined when end point criteria were achieved . RESULTS Suicidal behavior was significantly less in patients treated with clozapine vs olanzapine ( hazard ratio , 0.76 ; 95 % confidence interval , 0.58 - 0.97 ; P = .03 ) . Fewer clozapine-treated patients attempted suicide ( 34 vs 55 ; P = .03 ) , required hospitalizations ( 82 vs 107 ; P = .05 ) or rescue interventions ( 118 vs 155 ; P = .01 ) to prevent suicide , or required concomitant treatment with antidepressants ( 221 vs 258 ; P = .01 ) or anxiolytics or soporifics ( 301 vs 331 ; P = .03 ) . Overall , few of these high-risk patients died of suicide during the study ( 5 clozapine vs 3 olanzapine-treated patients ; P = .73 ) . CONCLUSIONS Clozapine therapy demonstrated superiority to olanzapine therapy in preventing suicide attempts in patients with schizophrenia and schizoaffective disorder at high risk for suicide . Use of clozapine in this population should lead to a significant reduction in suicidal behavior Typical antipsychotics have been reported to enlarge the cau date nucleus in schizophrenic patients . The atypical antipsychotic , clozapine , is associated with a decrease in cau date size in patients previously treated with typical antipsychotics . The present study investigates whether a change in cau date volume after switching from treatment with typical antipsychotics to treatment with clozapine is related to improvement in symptoms or tardive dyskinesia ( TD ) .  Twenty-six schizophrenic patients participated in this open study . Cau date nucleus volume and TD were assessed before discontinuing typical antipsychotics and after 24 weeks of treatment with clozapine . After discontinuing typical antipsychotics , symptoms were assessed in a 3 days drug-free period and subsequently once a month . Treatment with clozapine result ed in a decrease in cau date volume , improvement in symptoms and amelioration of TD . However , no difference in cau date volume changes was found between responders and non-responders to clozapine and no correlations were found between cau date volume changes and reduction of TD . In conclusion , this study replicates earlier findings that clozapine decreases cau date volume in patients previously treated with typical antipsychotics and suggests that this effect is unrelated to treatment response or to amelioration of TD Typical antipsychotic drugs act on the dopaminergic system , blocking the dopamine type 2 ( D2 ) receptors . Atypical antipsychotics have lower affinity and occupancy for the dopaminergic receptors , and a high degree of occupancy of the serotoninergic receptors 5-HT2A . Whether these different pharmacological actions produce different effects on brain structure remains unclear . We explored the effects of different types of antipsychotic treatment on brain structure in an epidemiologically based , nonr and omized sample of patients at the first psychotic episode . Subjects were recruited as part of a large epidemiological study ( ÆSOP : aetiology and ethnicity in schizophrenia and other psychoses ) . We evaluated 22 drug-free patients , 32 on treatment with typical antipsychotics and 30 with atypical antipsychotics .  We used high-resolution MRI and voxel-based methods of image analysis . The MRI analysis suggested that both typical and atypical antipsychotics are associated with brain changes . However , typicals seem to affect more extensively the basal ganglia ( enlargement of the putamen ) and cortical areas ( reductions of lobulus para central is , anterior cingulate gyrus , superior 
    Output:
    
In structural studies , the use of clozapine was associated with volume reductions in the basal ganglia , especially the cau date nucleus , where functional neuroimaging studies also found decreased perfusion .
In the frontal lobe , clozapine treatment was associated with increased gray matter volume and reduced perfusion .
CONCLUSION The results of the studies review ed suggest that the use of clozapine is associated with distinctive structural and functional neuroimaging findings that are not shared with other antipsychotics