Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We tested the hypothesis that basal ganglia dysfunction may be related to procedural learning impairment in schizophrenia. We determined the N-acetylaspartate/choline (NAA/Cho) ratio in the left striatal area in 11 young first-episode antipsychotic-naive patients and matched controls. Procedural learning was assessed by the four-disk version of the Tower of Hanoi. Analysis of variance showed that the number of moves and the execution time had a significant group effect (P=0.02, P<0.0001, respectively). Correlation analysis between procedural learning and the NAA/Cho ratio showed a negative significant correlation only in patients, measured by both time (P=0.006) and by moves (P=0.001). In summary, we found that schizophrenic patients have impaired procedural learning, and that this impairment is related to basal ganglia metabolism.
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PMID:Basal ganglia N-acetylaspartate correlates with the performance in the procedural task 'Tower of Hanoi' of neuroleptic-naive schizophrenic patients. 1287 37

The underlying neurobiology of emerging psychotic disorders is not well understood. Recent neuroimaging findings have suggested that some brain areas are affected prior to the onset of psychosis, while changes occur in other brain regions during the transition to illness. Further, previous research using magnetic resonance spectroscopy (MRS) has generally demonstrated that there are changes to the brain chemistry of patients with schizophrenia. However, it is unclear whether these changes are present prior to or at the onset of the disorder, and to what extent they are specific to schizophrenia. In this study, we assessed the left medial temporal and left dorsolateral prefrontal regions of 56 patients in their first episode of a psychotic disorder, 30 young people at ultra high-risk (UHR) of developing psychosis, and 21 healthy controls, using proton MRS. Six of the UHR group developed a first episode psychosis over the study period. No differences were identified between the first episode and control groups for any metabolite ratio in either region of interest. This may reflect intact neuronal circuits in the early phase of psychotic disorders. There were also no differences between the UHR and control groups for the medial temporal region. However, there was a significant elevation of the NAA/Creatine and the Choline/Creatine ratios in the dorsolateral prefrontal region of the UHR group, which was interpreted as a decline in creatine indicative of hypometabolism. This finding did not discriminate between those UHR individuals who later became psychotic and those who did not.
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PMID:Proton magnetic resonance spectroscopy in first episode psychosis and ultra high-risk individuals. 1498 20

In adult schizophrenia, magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) have revealed volumetric and metabolic defects in multiple brain regions, among them the anterior cingulate, frontal cortex, striatum, thalamus, parietal cortex, and frontal and parietal white matter. This study used proton magnetic resonance spectroscopic imaging ((1)H MRSI) to identify potential metabolic abnormalities in these regions in childhood-onset schizophrenia. (1)H MRSI was acquired at 1.5 T and 272 ms echo time in 11 children and adolescents with schizophrenia (aged 7-18 years; seven boys, four girls; all but two medicated) and 20 age-matched healthy controls (10 boys, 10 girls). Absolute levels of N-acetyl compounds (NAA), creatine plus phosphocreatine (Cr), and choline compounds (Cho) were compared among groups in each region. In schizophrenic patients relative to controls, Cr was 14.3% higher in superior anterior cingulate (mean of left and right hemispheres). Cho was higher in superior anterior cingulate (30.3%), frontal cortex (13.3%), and caudate head (13.5%). In the thalamus, there was also a diagnosis-by-gender interaction, whereby NAA was lower in patients for male but not for female subjects. Elevated Cr suggests abnormal local cell-energy demand and elevated Cho is consistent with a prior proposal that patients with early age-of-onset schizophrenia exhibit phospholipid membrane disturbances. Low NAA may reflect diminished neuronal integrity.
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PMID:1H MRSI evidence of metabolic abnormalities in childhood-onset schizophrenia. 1505 May 98

While several studies have suggested a relationship between the hippocampus and psychosis in schizophrenia, fewer studies have specifically investigated the presence of psychosis in mood disorders from a neurobiological perspective. Moreover, a limitation of these earlier studies is that the majority of them were performed in chronic patients. The present proton magnetic resonance spectroscopic imaging (1H-MRSI) study assessed neuronal integrity (as assessed with N-acetylaspartate, NAA) in the hippocampus of patients with a first episode of mood disorders with psychotic symptoms. We studied 17 patients and 17 healthy subjects matched for age and sex. Subjects underwent 1H-MRSI, and measures of NAA, choline-containing compounds (CHO), and creatine+phosphocreatine (CRE) in 11 brain regions were obtained, i.e. hippocampus (HIPPO), dorsolateral prefrontal cortex, superior temporal gyrus, inferior frontal gyrus, occipital cortex, anterior and posterior cingulate, centrum semiovale, prefrontal white matter, thalamus and putamen. NAA/CRE ratios in HIPPO of patients were significantly lower than in controls. Sporadic and non-hypothesis-driven results were found in occipital cortex and prefrontal white matter as a main effect of diagnosis, and in superior temporal gyrus as a hemisphere by diagnosis interaction. These results would not survive a Bonferroni correction for the number of ROIs. No correlations were found with the available demographic and clinical data. Therefore, hippocampal neuronal abnormalities are present at the onset of mood disorders with psychotic symptoms. These data suggest that neuronal abnormalities in HIPPO may be associated with psychosis in mood disorders. Since these data were obtained in patients at first episode, they cannot be explained by chronicity of illness or pharmacological treatment.
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PMID:Hippocampal neurochemical pathology in patients at first episode of affective psychosis: a proton magnetic resonance spectroscopic imaging study. 1531 16

Localized in vivo proton magnetic resonance spectroscopy (MRS) was performed to evaluate metabolic alterations in the right and left frontal lobe before and after antipsychotic treatment of schizophrenic patients (n=24) and a group of healthy normal subjects (n=20). Proton metabolic ratios obtained from the 8 cm3 voxels in the right and left frontal lobes were compared with the clinical assessment for each subject. There was no significant difference in the metabolic ratios between the right and the left frontal lobes in either the schizophrenic group or the control group, indicating no laterality. Compared with those of the normal control group, NAA/Cr ratio of the schizophrenic patients showed significantly lower value. The NAA/Cr ratio of the schizophrenic patients was not changed after antipsychotic treatment. The present study supports the 'hypofrontality' hypothesis of schizophrenia.
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PMID:Neuronal dysfunction of the frontal lobe in schizophrenia. 1536 17

N-Methyl-d-aspartate (NMDA) receptor antagonists are known to induce schizophrenia-like psychotic symptoms and cognitive deficits in humans, and have been shown to cause neuronal damage in the posterior cingulate gyrus (PCG) of rodents. Patients with chronic schizophrenia exhibit generalized cognitive deficits, but it remains unclear whether or not the PCG is related to their cognitive dysfunction. To determine what biochemical changes may occur in the PCG of patients with chronic schizophrenia, and to ascertain whether or not such abnormalities may be related to the incidence of cognitive deficits, we obtained cognitive scores and proton magnetic resonance spectra (MRS) from the PCG and the left and right medial temporal lobes (MTL) of 19 patients with schizophrenia and 18 age- and sex-matched normal healthy controls. Compared to the normal controls, the patients with chronic schizophrenia showed significantly worse cognitive performance on verbal and visual memory tests, verbal fluency tests, and the Trail Making Test. The ratio of N-acetylaspartate to creatine and phosphocreatine (NAA/Cr) in the PCG of the patients was significantly lower than that of the controls. Moreover, the NAA/Cr in the PCG of the healthy controls exhibited age-related decline, whereas in the patients with schizophrenia, the corresponding values were consistently low, regardless of age. These findings are thus in accord with current speculation about neuronal dysfunction in the PCG based on the NMDA hypofunction hypothesis regarding the pathophysiology of chronic schizophrenia.
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PMID:Posterior cingulate gyrus metabolic changes in chronic schizophrenia with generalized cognitive deficits. 1599 95

Numerous studies using proton magnetic resonance spectroscopy (1H-MRS) have detected signal changes in schizophrenia. However, most studies investigated relative concentrations such as N-acetylaspartate/creatine plus phosphocreatine (NAA/Cre) and choline-containing compounds/creatine plus phosphocreatine (Cho/Cre), and individual metabolite concentrations have not been clarified. Using absolute quantification measurement of 1H-MRS, the aim of the present paper was to demonstrate the changes in metabolite concentrations in the frontal lobe of patients with chronic schizophrenia. The 1H-MRS was performed in the left frontal lobe in 14 patients with schizophrenia and in 13 healthy comparison subjects. Individual MRS peak concentration was quantified based on a frequency-domain fitting program: LCModel. The scores on the Positive and Negative Symptoms Scale and Wisconsin Card Sorting Test were used for clinical assessment. The NAA concentration was reduced in schizophrenic patients (average, 7.94 mmol/L, t=2.28, P<0.05) compared with healthy subjects (average=8.45 mmol/L) while choline, creatine or NAA/Cre ratio did not show any differences. The reduction in NAA concentration had a significant correlation with the severity of negative symptoms (r=-0.536, P<0.05) and poor performance in Wisconsin Card Sorting Test (r=-0.544, P<0.05). Using quantitative MRS, decreased NAA concentration was confirmed in the left frontal lobe of schizophrenic patients and was demonstrated to be correlated with negative symptoms and cognitive dysfunction in schizophrenia.
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PMID:Quantitative magnetic resonance spectroscopy of schizophrenia: relationship between decreased N-acetylaspartate and frontal lobe dysfunction. 1673 55

The precision [coefficient of variation or CV (%) = 100SD/X] of single-voxel point resolved spectroscopic data was characterized bilaterally, in anterior cingulate and in hippocampus, at 4.0 T in a healthy subject. Data acquisition was replicated 10 times after voxel repositioning and readjusting higher order shims. Precision measurements show that the scan-to-scan precision is better in anterior cingulate than in hippocampus, with an average CV of 9.2% (for total NAA, tCho and Cr) in anterior cingulate and 13.9% in hippocampus. Variability measurements made by the same method in 24 healthy subjects and in 29 schizophrenia patients showed that there is substantial biological variability in metabolite levels, even in healthy subjects. Simple calculations suggest that more than 200 subjects would be needed to detect a 5% difference in NAA between patients and controls.
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PMID:Single-voxel 1H PRESS at 4.0 T: precision and variability of measurements in anterior cingulate and hippocampus. 1676 68

We used proton magnetic resonance spectroscopy (1H MRS) to examine biochemical characteristics of the brain tissue in subjects at risk for schizophrenia. Nineteen participants fulfilling research criteria for an early (n=10) or a late (n=9) at-risk syndrome, 21 patients with full disease according to DSM IV and 31 healthy control subjects were included in the study. Single-voxel 1H MRS was performed in the left frontal lobe, the anterior cingulate gyrus and the left superior temporal lobe. Subjects were followed longitudinally to detect conversion to schizophrenia. We observed a significant reduction of the metabolic ratios NAA/Cr and NAA/Cho in the left frontal lobe and of NAA/Cr in the anterior cingulate gyrus in both at-risk groups and in the schizophrenic patients compared with healthy controls. Those at-risk subjects, who converted to schizophrenia within the observation period, had a higher Cho/Cr and a lower NAA/Cho ratio in the anterior cingulate gyrus compared with non-converters. NAA/Cr did not differ between converters and non-converters. Six at-risk subjects were taking antidepressants, two were taking antipsychotics. There was no difference in any metabolic ratio in any region between at-risk subjects with and without medication. We conclude that the reduction of the neuronal marker NAA in the left prefrontal lobe and the anterior cingulate gyrus may represent a vulnerability indicator for schizophrenia in at-risk subjects, while elevated Cho in the anterior cingulate gyrus may be a predictor for conversion from the prodromal state to the full disease.
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PMID:Proton magnetic resonance spectroscopy in subjects at risk for schizophrenia. 1684 71

Functional and structural neuroimaging help us to compare the brains of schizophrenic patients and controls, moreover they let us observe the changes with treatment. Longitudinal studies comparing patients with typical and atypical antipsychotics have been useful in understanding the effects of these antipsychotic medications on brain function. In general, atypical antipsychotics are suggested to have greater normalizing effects on brain function than typical, although the results are controversial. In particular, clozapine appears to act more selectively than typical antipsychotics on the prefrontal region, an area of special relevance in higher cognitive functions and schizophrenia. The study of anatomic and functional brain variables associated with clozapine response in schizophrenia may help to identify patients who are most likely to benefit from clozapine treatment. We investigated the effect of clozapine on regional cerebral blood flow and (1)H MRS findings and studied their relationship with treatment response. Clozapine increased frontal/basal ganglia perfusion ratio in treatment-responders. In addition, NAA/Cre ratio has increased and Cho/Cre has decreased in dorsolateral prefrontal cortex after 8 weeks of clozapine treatment. The results of the study will be discussed in the light of current literature. These findings can contribute to better understanding of mechanism of action of clozapine.
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PMID:The effect of clozapine on neuroimaging findings in schizophrenia. 1800 Apr 91


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