***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: We detected and mapped a dynamically spreading wave of gray matter loss in the brains of patients with Alzheimer 's disease ( AD ) . The loss pattern was visualized in four dimensions as it spread over time from temporal and limbic cortices into frontal and occipital brain regions , sparing sensorimotor cortices . The shifting deficits were asymmetric ( left hemisphere > right hemisphere ) and correlated with progressively declining cognitive status ( p < 0.0006 ) . Novel brain mapping methods allowed us to visualize dynamic patterns of atrophy in 52 high-resolution magnetic resonance image scans of 12 patients with AD ( age 68.4 ± 1.9 years ) and 14 elderly matched controls ( age 71.4 ± 0.9 years ) scanned longitudinally ( two scans ; interscan interval 2.1 ± 0.4 years ) . A cortical pattern matching technique encoded changes in brain shape and tissue distribution across subjects and time . Cortical atrophy occurred in a well defined sequence as the disease progressed , mirroring the sequence of neurofibrillary tangle accumulation observed in cross sections at autopsy . Advancing deficits were visualized as dynamic maps that change over time . Frontal regions , spared early in the disease , showed pervasive deficits later ( > 15 % loss ) . The maps distinguished different phases of AD and differentiated AD from normal aging . Local gray matter loss rates ( 5.3 ± 2.3 % per year in AD v 0.9 ± 0.9 % per year in controls ) were faster in the left hemisphere ( p < 0.029 ) than the right . Transient barriers to disease progression appeared at limbic/frontal boundaries . This degenerative sequence , observed in vivo as it developed , provides the first quantitative , dynamic visualization of cortical atrophic rates in normal elderly population s and in those with dementia 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 OBJECTIVE Multicenter trials with the novel antipsychotic risperidone have suggested a st and ard dose of 6 mg/day . However , a dose producing the highest response rate in fixed-dose studies is likely to exceed the minimal effective dose in most patients . The aim of this positron emission tomography ( PET ) study was to suggest a minimal effective dose of risperidone based on measurements of dopamine D2 and serotonin 5-HT2A receptor occupancy . METHOD Eight first-episode or drug-free schizophrenic patients were treated with risperidone , 6 mg/day , for 4 weeks and then 3 mg/day for 2 weeks . PET was performed after 4 and 6 weeks , with [11C]raclopride to measure D2 receptor occupancy and [11C]N-methylspiperone to measure 5-HT2A receptor occupancy . RESULTS Seven patients completed the study and responded to treatment with risperidone . No patient had extrapyramidal side effects at the time of inclusion in the study . At the 6-mg/day dose , mean D2 receptor occupancy was 82 % ( range = 79%-85 % ) , 5-HT2A receptor occupancy was 95 % ( range = 86%-109 % ) , and six patients had developed extrapyramidal side effects . After dose reduction to 3 mg/day , D2 receptor occupancy was 72 % ( range = 53%-78 % ) , and 5-HT2A receptor occupancy was 83 % ( range = 65%-112 % ) . Three patients had extrapyramidal side effects at this time . CONCLUSIONS Treatment with risperidone , 6 mg/day , is likely to induce unnecessarily high D2 receptor occupancy , with a consequent risk of extrapyramidal side effects . High 5-HT2A receptor occupancy did not prevent extrapyramidal side effects completely . The authors previously suggested an optimal interval for D2 receptor occupancy of 70%-80 % . To achieve this , resperidone , 4 mg/day , should be a suitable initial dose for antipsychotic effect with a minimal risk of extrapyramidal side effects in most patients Neurodevelopmental models for the pathology of schizophrenia propose both polygenetic and environmental risks , as well as early ( pre/perinatal ) and late ( usually adolescent ) developmental brain abnormalities . With the use of brain mapping algorithms , we detected striking anatomical profiles of accelerated gray matter loss in very early-onset schizophrenia ; surprisingly , deficits moved in a dynamic pattern , enveloping increasing amounts of cortex throughout adolescence . Early-onset patients were rescanned prospect ively with MRI , at 2-year intervals at three time points , to uncover the dynamics and timing of disease progression during adolescence . The earliest deficits were found in parietal brain regions , supporting visuospatial and associative thinking , where adult deficits are known to be mediated by environmental ( nongenetic ) factors . Over 5 years , these deficits progressed anteriorly into temporal lobes , engulfing sensorimotor and dorsolateral prefrontal cortices , and frontal eye fields . These emerging patterns correlated with psychotic symptom severity and mirrored the neuromotor , auditory , visual search , and frontal executive impairments in the disease . In temporal regions , gray matter loss was completely absent early in the disease but became pervasive later . Only the latest changes included dorsolateral prefrontal cortex and superior temporal gyri , deficit regions found consistently in adult studies . These emerging dynamic patterns were ( i ) controlled for medication and IQ effects , ( ii ) replicated in independent groups of males and females , and ( iii ) charted in individuals and groups . The result ing mapping strategy reveals a shifting pattern of tissue loss in schizophrenia . Aspects of the anatomy and dynamics of disease are uncovered , in a changing profile that implicates genetic and nongenetic patterns of deficits While haloperidol is still widely used in the treatment of psychoses , the optimal daily dose remains a topic of controversy , particularly in first-episode psychosis . Previous studies have suggested that doses as low as 2 mg/d may be effective , whereas others have indicated superiority for higher over lower doses . This double-blinded , r and omized controlled study compared the efficacy and tolerability of 2 vs. 8 mg/d of haloperidol over 6 wk in 40 subjects with first-episode psychosis . Both treatments were equally effective in reducing the PANSS Total and subscale scores . The low dose of haloperidol was better tolerated , with fewer extrapyramidal side-effects , less frequent use of anticholinergic medication and smaller elevations in prolactin levels . Using a low dose of haloperidol is at least as effective as , and better tolerated than a high dose of haloperidol in the treatment of first-episode psychosis OBJECTIVE A follow-up study of patients with schizophrenia was conducted to examine change in striatal volumes and extrapyramidal symptoms after a change in medication . METHOD Thirty-seven patients with schizophrenia and 23 healthy volunteers were examined . Patients at baseline receiving typical antipsychotics ( N=10 ) or risperidone but exhibiting limited response ( N=13 ) were switched to treatment with  olanzapine . Patients receiving risperidone and exhibiting a good response ( N=14 ) continued treatment with risperidone . Cau date , putamen , and pallidal volumes were assessed with magnetic resonance imaging . The Extrapyramidal Symptoms Rating Scale was used to assess clinical signs and symptoms . RESULTS At baseline , basal ganglia volumes in patients treated with typical antipsychotics were greater than in healthy subjects ( putamen : 7.0 % larger ; globus pallidus : 20.7 % larger ) . After the switch to olanzapine , putamen and globus pallidus volumes decreased ( 9.8 % and 10.7 % , respectively ) and did not differ from those of healthy subjects at the follow-up evaluation . Akathisia was also reduced . In the patients receiving risperidone at baseline , basal ganglia volumes did not differ between those exhibiting good and poor response , and no significant volume changes were observed in subjects with poor risperidone response after the switch to olanzapine treatment . CONCLUSIONS Olanzapine reversed putamen and globus pallidus enlargement induced by typical antipsychotics but did not alter volumes in patients previously treated with risperidone . Changes in striatal volumes related to typical and atypical antipsychotics may represent an interactive effect between individual medications and unique patient characteristics BACKGROUND The midbrain contains the perikarya of all the dopamine neurons in the human brain . Although other neurochemicals may well be involved , dopamine dysregulation is central in the pathophysiology of psychosis . Despite this , few imaging studies have evaluated the morphology of the midbrain . METHODS Using high-resolution magnetic resonance imaging , morphology of three posterior fossa and brain stem structures were measured : midbrain , pons , and medulla . The patient sample consisted of 50 men with schizophrenia , matched by gender and age to 50 healthy control subjects . RESULTS Patients had significantly smaller midbrain measures compared with control subjects . There were no differences between groups in measures of pons or medulla . Furthermore , midbrain size was significantly and inversely correlated with positive symptoms and cumulative neuroleptic exposure , but not with negative or disorganized symptoms . After controlling for the effect of cumulative neuroleptic exposure , the relationship between midbrain morphology and positive symptoms remained significant . CONCLUSIONS Midbrain morphology of patients with schizophrenia is abnormal , being smaller in patients compared with control subjects . Although this appears to be specifically related to psychotic symptoms , there is also a robust medication effect , with greater exposure to neuroleptics being associated with greater morphologic abnormality . We discuss the role of dopaminergic dysregulation and possible neural circuit involvement Positron Emission Tomography ( PET ) imaging of regional cerebral blood flow ( rCBF ) provides an in vivo method for sup study ing brain function . We used [15O]H2O PET to assess the effect of antipsychotic medications on rCBF in 17 subjects with schizophrenia . Each subject was scanned while receiving antipsychotic medication , and after having been withdrawn from antipsychotic medic 
    Output:
    
The results suggest that antipsychotics  act regionally rather than globally on the brain .
These volumetric changes are of a greater magnitude in association with typical than with atypical antipsychotic use .
Indeed , there is evidence of a specific effect of antipsychotic type on the basal ganglia , with typicals specifically increasing the volume of these structures .
Differential effects of antipsychotic type may also be present on the thalamus and the cortex , but data on these and other brain areas are more equivocal .
Antipsychotic treatment potentially contributes to the brain structural changes observed in psychosis .