***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: This study evaluates the effects of ketamine on healthy and schizophrenic volunteers ( SVs ) in an effort to define the detailed behavioral effects of the drug in a psychosis model . We compared the effects of ketamine on normal and SVs to establish the comparability of their responses and the extent to which normal subjects might be used experimentally as a model . Eighteen normal volunteers ( NVs ) and 17 SVs participated in ketamine interviews . Some ( n = 7 NVs ; n = 9 SVs ) had four sessions with a 0.1–0.5 mg/kg of ketamine and a placebo ; others ( n = 11 NVs ; n = 8 SVs ) had two sessions with one dose of ketamine ( 0.3 mg/kg ) and a placebo . Experienced research clinicians used the BPRS to assess any change in mental status over time and documented the specifics in a timely way . In both volunteer groups , ketamine induced a dose-related , short ( < 30 min ) increase in psychotic symptoms . The scores of NVs increased on both the Brief Psychiatric Rating Scale ( BPRS ) psychosis subscale ( p = .0001 ) and the BPRS withdrawal subscale ( p = .0001 ) , whereas SVs experienced an increase only in positive symptoms ( p = .0001 ) . Seventy percent of the patients reported an increase ( i.e. , exacerbation ) of previously experienced positive symptoms . Normal and schizophrenic groups differed only on the BPRS withdrawal score . The magnitude of  ketamine-induced changes in positive symptoms was similar , although the psychosis baseline differed , and the dose-response profiles over time were superimposable across the two population s. The similarity between ketamine-induced symptoms in SVs and their own positive symptoms suggests that ketamine provides a unique model of psychosis in human volunteers . The data suggest that the phencyclidine ( PCP ) model of schizophrenia maybe a more valid human psychosis/schizophrenia drug model than the amphetamine model , with a broader range of psychotic symptoms . This study indicates that NVs could be used for many informative experimental psychosis studies involving ketamine interviews The purpose of this study was to assess further the effect of amphetamine on negative symptoms of schizophrenia . Thirty-seven schizophrenic males meeting DSM-III criteria were rated with the Brief Psychiatric Rating Scale , the Abrams and Taylor Scale , and the Abnormal Involuntary Movements Scale before and after double-blind administration of either amphetamine ( n=26 ) or placebo ( n=11 ) . Our results indicated that amphetamine administration generally did not improve negative symptoms , even when accounting for changes in positive symptoms . However , greater baseline negative symptoms were associated with a modest diminution after amphetamine treatment . Therefore , amphetamine may modestly improve negative symptoms in those schizophrenics in whom this symptomatology is more severe OBJECTIVE The authors sought to determine if an acute dose of dextroamphetamine might have positive effects on affect and cognition in schizophrenic patients maintained on a regimen of haloperidol  and , if so , what variables might predict such improvements . METHOD Twenty-one patients with chronic schizophrenia who were hospitalized on a research ward received a single oral dose of dextroamphetamine ( 0.25 mg/kg ) in a double-blind , placebo-controlled , crossover study . All patients were receiving 0.4 mg/kg per day of haloperidol .  Cognitive tests , motor tests , global ratings , mood ratings , and videotape ratings were used to determine the effect of the coadministration of these drugs . Ventricle-brain ratios derived from CT scans were used to predict response to the coadministration of these drugs . RESULTS Amphetamine improved performance on a measure of concept formation on the Wisconsin Card Sorting Test but did not result in changes in performance on tests of memory or attention . As a group , the patients were more active and performed psychomotor tests more quickly while receiving amphetamine . Six patients were judged by clinical raters to have improved in terms of affect , cooperation , and engagement with the environment . Improvement was associated with enlarged cerebral ventricles and increases in blink rate from the placebo to the active drug condition . No patient unequivocally worsened . CONCLUSIONS These results may be consistent with the theory that coadministration of amphetamine and haloperidol produces relatively selective enhancement of cortical dopaminergic activity . However , because of the acute nature of the trial and the specialized research environment in which it was conducted , the authors do not advocate amphetamine as a routine clinical treatment of schizophrenia Changes in regional cerebral blood flow and behavioral and physiological indices were monitored after intravenous administration of d-amphetamine sulfate and placebo in groups of patients with schizophrenia and normal volunteers .  Amphetamine administration was associated with decreased anxiety , emotional withdrawal , depressed mood , blunted affect and increased excitement in the patients . Subjects who received amphetamine showed significant increases in systolic and diastolic blood pressure and reduction in end-tidal carbon dioxide . Post-amphetamine cerebral blood flow was decreased equally in both patients and controls . The blood flow change , however , did not show any regional variations The response of plasma beta-endorphin ( ir ) to infusions of r and omly assigned d-amphetamine ( 20 mg ) and placebo was studied in eight schizophrenic patients . Although there was no statistically significant difference between the response to d-amphetamine and placebo , significant increases in plasma beta-endorphin ( ir ) levels were observed following each infusion . Although heterogeneity in beta-endorphin ( ir ) response was observed , individual differences did not relate to clinical variables such as abnormalities on computed tomography or " process-reactive " distinctions . An excessive beta-endorphin response to placebo in schizophrenia is discussed The authors examined the specific behavioral and biochemical effects of intravenous methylpheni date in a sample of schizophrenic and nonschizophrenic patients . Twenty drug-free patients participated in a double-blind , placebo r and omized study of methylpheni date , with multiple sample s of plasma homovanillic acid ( HVA ) and serum growth hormone ( GH ) obtained during the infusion procedure . Methylpheni date caused a significant increase in positive symptoms that was relatively specific to the schizophrenic patients and was evident even in those with otherwise dormant symptomatology . When behavioral response was correlated with the biochemical responses ( i.e. , changes in plasma HVA and GH ) , there was a significant positive relationship between the increase in the BPRS-positive symptoms as well as the hostility/suspiciousness factor , and the increase in GH . These results suggest that the expression of psychotic symptoms may be associated with increased dopaminergic postsynaptic sensitivity , although the nonspecific nature of methylpheni date 's actions discourages a stronger interpretation of the results The pathophysiology of schizophrenia may be related directly or indirectly to abnormal dopaminergic activity . Both subcortical excess and frontal cortical deficiency of dopamine have been suggested , and primary or downstream failures of dopamine activation to the prefrontal cortex has been posited to explain some of the cognitive deficiencies in schizophrenia patients . Although the prefrontal cortex may also be a site for the disruption of smooth pursuit eye movements ( SPEM ) , the most substantially described psychophysiological marker for schizophrenia vulnerability , no relationship of SPEM to dopaminergic activity has been demonstrated . In this study we explored the effect of altered dopamine function on SPEM quality through pharmacological manipulation of catecholamine tone in 11 healthy subjects . The subjects had SPEM measured at baseline , and under challenge conditions including amphetamine ( 0.3 mg/kg ) , haloperidol ( 2 mg ) , placebo , and combined amphetamine with haloperidol . Changes in the profile of mood scale ( POMS ) confirmed the expected subjective central nervous system effects the agents . Placebo and amphetamine had no effect on qualitative ratings of SPEM , but haloperidol , alone and in combination with amphetamine , disrupted eye tracking , producing a pattern of small saccadic intrusions characteristic of patients with schizophrenia . These findings link dopaminergic blockade with SPEM disruption in normal subjects The acute pharmacological actions of methylpheni date , a potent psychotogenic stimulant , were studied by measuring plasma homovanillic acid ( HVA ) and serum growth hormone ( GH ) as indices of presynaptic and postsynaptic functions , respectively . Twenty psychiatric in patients participated in a double-blind , placebo-r and omized study of methylpheni date infusion . Multiple sample s of plasma HVA and GH were measured before and up to 24 hours after both methylpheni date and placebo infusions . There was a robust and significant GH response during the 2-hour postmethylpheni date period when compared to placebo . The peak response was significantly greater in male patients than in female patients . Although there were no changes in plasma HVA during the 2 hours following the infusion , there was a significant decrease in HVA 24 hours after methylpheni date as compared to preinfusion baseline values . Plasma HVA values also tended to be lower 24 hours after methylpheni date when compared to the corresponding postplacebo value . Schizophrenic patients did not differ significantly from nonschizophrenic patients in their physiological or biochemical responses Behavioral sensitization is the process whereby intermittent stimulant exposure produces a time-dependent , enduring , and progressively more robust behavioral response . This process serves as a model for the development of psychosis , but has been little studied in humans . The authors report results from a double-blind , placebo-controlled study of repeated d-amphetamine challenges in 13 patients with first-episode manic or schizophrenic psychosis . Each patient received two daily doses of d-amphetamine ( 0.25 mg/kg ) separated by 48 hours that alternated with two daily doses of matched placebo .  Symptoms ( activity/energy level , mood , rate and amount of speech , and severity of psychosis ) and eye-blink rates were measured hourly for 5 hours following drug administration . In contrast to results from previous work in normal volunteers , none of the measures demonstrated the progressive increase following the second amphetamine dose as compared to the first dose that characterizes sensitization . These results suggest that patients with psychosis are already maximally sensitized , so can not exhibit progressive behavioral enhancement following repeated stimulant challenges , or that patients with psychosis do not sensitize To explore the role of monoamines on cerebral function during specific prefrontal cognitive activation , we conducted a double-blind placebo- controlled crossover study of the effects of 0.25 mg/kg oral dextroamphetamine on regional cerebral blood flow ( rCBF ) as determined by 133Xe dynamic single-photon emission-computed tomography ( SPECT ) during performance of the Wisconsin Card Sorting Test ( WCST ) and a sensorimotor control task . Ten patients with chronic schizophrenia who had been stabilized for at least 6 weeks on 0.4 mg/kg haloperidol participated . Amphetamine produced a modest , nonsignificant , task- independent , global reduction in rCBF . However , the effect of amphetamine on task-dependent activation of rCBF ( i.e. , WCST minus control task ) was striking . Whereas on placebo no significant activation of rCBF was seen during the WCST compared with the control task , on amphetamine significant activation of the left dorsolateral prefrontal cortex ( DLPFC ) occurred ( p = 0.0006 ) . Both the mean number of correct responses and the mean conceptual level increased ( p less than 0.05 ) with amphetamine relative to placebo . In addition , with amphetamine , but not with placebo , a significant correlation ( p = - 0.71 ; p less than 0.05 ) emerged between activation of DLPFC rCBF and performance of the WCST task . These findings are consistent with animal models in which mesocortical catecholaminergic activity modulates and enhances the signal-to-noise ratio of evoked cortical activity The dopamine hypothesis of schizophrenia cl aims that increased dopamine activity underlies psychotic behavior . This hypothesis gets major support from the reported d-amphetamine-induced worsening of psychosis , because amphetamine increases dopamine activity in the brain . Dopamine receptor supersensitivity has been shown to be present in animals during the postneuroleptic period . In this study the postulated relationships between psychotic decompensation as observed after d-amphetamine infusion and the dopamine receptor supersensitivity expected to be present during the neuroleptic withdrawal period were examined . Twenty milligrams of d-amphetamine administered intravenously did not cause a stronger psychotogenic effect in 12 schizophrenic patients . One week after discontinuation of pimozide treatment , the d-amphetamine-induced change as indicated by the Brief Psychiatric Rating Scale ( BPRS ) paranoid disturbance cluster score , was not significantly different from the response to a similar infusion during the drug-free state . Unexpectedly , the increase in the BPRS mannerisms and posturing item and in the pulse rate response to d-amphetamine  were decreased . These results raise questions about the role of dopamine in d-amphetamine effects and suggest postneuroleptic dopamine receptor subsensitivity . They challenge a 
    Output:
    
Addition of more studies may clarify reasons why people with schizophrenia persist in taking these harmful stimulants