***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: BACKGROUND Disturbances of N-methyl-D-aspartate ( NMDA ) receptor-mediated glutamatergic neurotransmission may play an important role in the pathophysiology of negative symptoms of schizophrenia . Glycine , a small nonessential amino acid , functions as an obligatory coagonist at NMDA receptors through its action at a strychnine-insensitive binding site on the NMDA receptor complex . Glycine-induced augmentation of NMDA receptor-mediated neurotransmission may thus offer a potentially safe and feasible approach for ameliorating persistent negative symptoms of schizophrenia . METHODS Twenty-two treatment-resistant schizophrenic patients participated in a double-blind , placebo-controlled , 6-week , crossover treatment trial with 0.8 g/kg per day of glycine added to their ongoing antipsychotic medication . Clinical assessment s , including the Brief Psychiatric Rating Scale ( BPRS ) , the Positive and Negative Syndrome Scale ( PANSS ) , the Simpson-Angus Scale for Extrapyramidal Symptoms , and the Abnormal Involuntary Movement Scale , were performed biweekly throughout the study . Clinical laboratory values and amino acid serum levels were monitored . RESULTS Glycine treatment was well tolerated and induced increased glycine ( P=.001 ) and serine ( P=.001 ) serum levels .  Glycine administration result ed in ( 1 ) a significant ( P<.001 ) 30%+/-16 % reduction in negative symptoms , as measured by the PANSS , and ( 2 ) a significant ( P<.001 ) 30%+/-18 % improvement in the BPRS total scores . The improvement in negative symptoms was unrelated to alterations in extrapyramidal effects or symptoms of depression . Low pretreatment glycine serum levels significantly predicted ( r= 0.80 ) clinical response . CONCLUSION These findings support hypoglutamatergic hypotheses of schizophrenia and suggest a novel approach for the pharmacotherapy of negative symptoms associated with this illness BACKGROUND Hypofunction of N-methyl-D-aspartate ( NMDA ) subtype glutamate receptor has been implicated in the pathophysiology of schizophrenia .  D-serine is a full agonist of the glycine site of NMDA receptor , an endogenous cotransmitter enriched in corticolimbic regions and distributed in parallel with NMDA receptor . Supplementation of D-serine may improve the symptoms of schizophrenia . METHODS Thirty-one Taiwanese schizophrenic patients enrolled in a 6-week double-blind ,  placebo-controlled trial of D-serine ( 30 mg/kg/day )  , which was added to their stable antipsychotic regimens . Of these , 28 completed the trial .  Measures of clinical efficacy , side effects , and serum levels of amino acids and D-serine  were determined every other week .  Wisconsin Card Sorting Test ( WCST ) was performed at the beginning and end of the trial . RESULTS Patients who received D-serine treatment revealed significant improvements in their positive , negative , and cognitive symptoms as well as some performance in WCST . D-serine levels at week 4 and 6 significantly predicted the improvements . D-serine was well tolerated and no significant side effects were noted . CONCLUSIONS The significant improvement with the D-serine further supports the hypothesis of NMDA receptor hypofunction in schizophrenia . Given the effects of D-serine on positive symptoms , a trial of D-serine alone in schizophrenia should be considered We administered ketamine to schizophrenic individuals in a double-blind , placebo-controlled design using a range of subanesthetic doses ( 0.1 , 0.3 , and 0.5 mg/kg ) to evaluate the nature , dose characteristics , time course , and neuroleptic modulation of N-methyl-D-aspartate ( NMDA ) antagonist action on mental status in schizophrenia . Ketamine induced a dose-related , short ( < 30 minutes ) worsening in mental status in the haloperidol-treated condition , reflected by a significant increase in BPRS total score for the 0.3 mg/kg ( p = . 005 ) and 0.5 mg/kg ( p = . 01 ) challenges . Positive symptoms ( hallucinations , delusions , thought disorder ) , not negative symptoms accounted for these changes . These ketamine-induced psychotic symptoms were strikingly reminiscent of the subject 's symptoms during active episodes of their illness . Results from six patients who were retested in the same design after being neuroleptic-free for 4 weeks failed to indicate that haloperidol blocks ketamine-induced psychosis . Several subjects evidence d delayed or prolonged ( 8–24 hours ) psychotomimetic effects such as worsening of psychosis with visual hallucinations . These data suggest that antagonism of NMDA-sensitive glutamatergic transmission in brain exacerbates symptoms of schizophrenia BACKGROUND First-degree relatives of persons with schizophrenia carry elevated genetic risk for the illness and show deficits on high-load information processing tasks . We used functional magnetic resonance imaging ( fMRI ) to test whether nonpsychotic relatives show altered functional activation in the prefrontal cortex ( PFC ) , thalamus , hippocampus , and anterior cingulate during a working memory task requiring interference resolution . METHODS Twelve nonpsychotic relatives of persons with schizophrenia and 12 healthy control subjects were administered an auditory , verbal working memory version of the Continuous Performance Test during fMRI . An asymmetric , spin-echo , T2 * -weighted sequence ( 15 contiguous , 7-mm axial slices ) was acquired on a full-body MR scanner . Data were analyzed by Statistical Parametric Mapping ( SPM ) . RESULTS Compared with control subjects , relatives showed greater task-elicited activation in the PFC and the anterior and dorsomedial thalamus . When task performance was controlled , relatives showed significantly greater activation in the anterior cingulate . When effects of other potentially confounding variables were controlled , relatives generally showed significantly greater activation in the dorsomedial thalamus and anterior cingulate . CONCLUSIONS This pilot study suggests that relatives of persons with schizophrenia have subtle differences in brain function in the absence of psychosis . These differences add to the growing literature identifying neurobiological vulnerabilities to schizophrenia Glycine is an agonist at brain N-methyl-D-aspartate receptors and crosses the blood-brain barrier following high-dose oral administration . In a previous study , significant improvements in negative and cognitive symptoms were observed in a group of 21 schizophrenic patients receiving high-dose glycine in addition to antipsychotic treatment .  This study evaluated the degree to which symptom improvements might be related to alterations in antipsychotic drug levels in an additional group of 12 subjects .  Glycine treatment was associated with an 8-fold increase in serum glycine levels , similar to that observed previously . A significant 34 % reduction in negative symptoms was observed during glycine treatment . Serum antipsychotic levels were not significantly altered . Significant clinical effects were observed despite the fact that the majority of subjects were receiving atypical antipsychotics ( clozapine  or olanzapine ) . As in earlier studies , improvement persisted following glycine discontinuation BACKGROUND To characterize further behavioral , cognitive , neuroendocrine , and physiological effects of subanesthetic doses of ketamine hydrochloride in healthy human subjects .  Ketamine , a phencyclidine hydrochloride derivative , is a dissociative anesthetic and a noncompetitive antagonist of the N-methyl-D-aspartate subtype of excitatory amino acid receptor . METHODS Nineteen healthy subjects recruited by advertisements from the community participated in this r and omized , double-blind , placebo-controlled study . Subjects completed three test days involving the 40-minute intravenous administration of placebo , ketamine hydrochloride ( 0.1 mg/kg ) , or ketamine hydrochloride ( 0.5 mg/kg ) . Behaviors associated with the positive and negative symptoms of schizophrenia were assessed by using the Brief Psychiatric Rating Scale . Changes in perception and behaviors associated with dissociative states were assessed by the Perceptual Aberration Subscale of the Wisconsin Psychosis Proneness Scale and the Clinician-Administered Dissociative States Scale . Cognitive function was assessed by using the ( 1 ) Mini-Mental State Examination ; ( 2 ) tests sensitive to frontal cortical dysfunction , including a continuous performance vigilance task , a verbal fluency task , and the Wisconsin Card Sorting Test ; and ( 3 ) tests of immediate and delayed recall . Plasma levels of cortisol , prolactin , homovanillic acid , and 3-methoxy-4-hydroxyphenethyleneglycol were measured . RESULTS Ketamine ( 1 ) produced behaviors similar to the positive and negative symptoms of schizophrenia ; ( 2 ) elicited alterations in perception ; ( 3 ) impaired performance on tests of vigilance , verbal fluency , and the Wisconsin Card Sorting Test ; ( 4 ) evoked symptoms similar to dissociative states ; and ( 5 ) preferentially disrupted delayed word recall , sparing immediate recall and postdistraction recall .  Ketamine had no significant effect on the Mini-Mental State Examination at the doses studied . Ketamine also had no effect on plasma 3-methoxy-4-hydroxyphenethyleneglycol levels , although it blunted a test day decline in plasma homovanillic acid levels at the higher dose . It also dose dependently increased plasma cortisol and prolactin levels .  Ketamine produced small dose-dependent increases in blood pressure . CONCLUSIONS These data indicate that N-methyl-D-aspartate antagonists produce a broad range of symptoms , behaviors , and cognitive deficits that resemble aspects of endogenous psychoses , particularly schizophrenia and dissociative states 
    Output:
    
The extant data suggest that abnormalities of the glutamate receptors as well as other molecules involved in glutamatergic neurotransmission ( including glutamate transporters and associated proteins , N-methyl D-aspartate ( NMDA ) receptor-associated intracellular signaling proteins , and glutamatergic enzymes ) are found within the thalamus in schizophrenia .
These and future findings may represent potential novel targets for antipsychotic drugs to ameliorate the symptoms of schizophrenia