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)

HPLC and gas chromatography-mass spectrometry analyses of 18 amino acids, N-acetylaspartate, N-acetylaspartylglutamate, and 5-hydroxyindoleacetic acid, derived from serotonin, and homovanillic acid, derived from dopamine, were performed in CSF collected from a group of patients with schizophrenia who either had been drug free for at least 1 year (n = 5) or were drug naive for psychotropic drugs (n = 21) and in 15 control subjects. Significant differences were found only for taurine (15% lower in the patients) and isoleucine (7% higher). A number of unidentified substances were detected, one of which proved to be markedly reduced (16%) among the schizophrenic patients. Liquid chromatography-mass spectrometry with continuous flow-fast atom bombardment interface allowed us to identify this substance as gamma-glutamylglutamine. The decreased level of gamma-glutamylglutamine may reflect a deficiency in the gamma-glutamyltransferase system, a system probably involved in glutamate uptake, or a deficiency in glutamine, an important precursor of releasable glutamate. Although glutamate was nonsignificantly reduced in the patients, it was one of the five substances (including gamma-glutamylglutamine) that were necessary for the best discrimination between the schizophrenic patients and the controls. These findings support the notion that the glutamatergic system is affected in schizophrenic disorders. In addition, they underscore the need to apply rigid bioanalytical techniques and use drug-naive patients to gain in-depth information on the pathophysiology of brain disorders such as schizophrenia.
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PMID:gamma-Glutamylglutamine and taurine concentrations are decreased in the cerebrospinal fluid of drug-naive patients with schizophrenic disorders. 759 63

To examine metabolic changes in the left basal ganglia in chronic schizophrenia, we performed proton magnetic resonance spectroscopy (1H-MRS) in 21 medicated schizophrenic patients and 21 gender and age-matched normal controls. Compared to the normal subjects, the schizophrenic patients showed a significantly increased level of choline containing compounds (Cho) (t = 2.60, p < 0.05) and ratio of Cho to N-acetylaspartate (NAA) (t = 2.46, p < 0.05) in the left basal ganglia. No significant correlation was observed between the 1H-MRS measurements in the left basal ganglia and clinical symptom scores as evaluated using the Brief Psychiatric Rating Scale (BPRS). The chlorpromazine equivalent neuroleptic dosage was positively correlated with the level of NAA (r = 0.38, p < 0.05) and negatively correlated with the Cho/NAA ratio (r = -0.34, p < 0.05). These findings suggest that these changes in metabolites in the left basal ganglia may reflect some of the functional and morphological abnormalities reported previously for the brain in schizophrenia.
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PMID:Proton magnetic resonance spectroscopy of the basal ganglia in patients with schizophrenia: a preliminary report. 890 87

The level of the 1H metabolites in the left dorsolateral prefrontal region of schizophrenia patients at different stages of illness were measured in vivo using a short echo time spectroscopy technique. During both the early onset and chronic stages, normal N-acetylaspartate levels were observed, which suggests that these patients had no significant neuronal cell damage and/or loss. The in vivo measurements of glutamate in the first-episode, drugnaive patients failed to provide convincing evidence for the involvement of the glutamatergic system in the dorsolateral prefrontal region. Significant differences in the glutamine levels were observed in the acutely medicated and chronic patients; however, the interpretation of these differences requires further study.
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PMID:An in vivo proton magnetic resonance spectroscopy study of schizophrenia patients. 893 14

Previous research has found structural and functional abnormalities in the temporal lobes of schizophrenic patients, often with greater impairment on the left side. This study applied proton MRS to both right and left temporal lobes of schizophrenic patients and normal control subjects. Reductions in the NAA/Cr ratio were found bilaterally for schizophrenic patients as compared to normal controls, and may be associated with reduced neuronal integrity. These results strengthen the evidence for biochemical abnormalities in the temporal lobes in schizophrenia.
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PMID:Proton magnetic resonance spectroscopy of the temporal lobes in schizophrenics and normal controls. 914 96

The authors measured N-acetylaspartate (NAA, a putative neuronal marker), choline and creatine in the anterior cingulate region of 26 schizophrenic patients and 16 control subjects using in vivo proton magnetic resonance spectroscopic imaging (1H MRSI). Relative to the control group, the patients with schizophrenia demonstrated significantly lower NAA in both the right and left anterior cingulate regions. There was no association between NAA and duration of illness or medication dosage. No group differences or lateralized asymmetries in choline or creatine were noted. The NAA findings provide support for either neuronal dysfunction or neuronal loss in the anterior cingulate region in schizophrenia. The absence of choline signal elevation does not support accelerated turnover of membrane phospholipids which might be expected if there were ongoing neuronal atrophy or neuronal necrosis.
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PMID:Proton magnetic resonance spectroscopy of the anterior cingulate region in schizophrenia. 937 96

There is mounting evidence, primarily from research in experimental animals, that the dipeptide N-acetylaspartylglutamate (NAAG) and its metabolic enzyme, N-acetylated alpha-linked acid dipeptidase (NAALADase), are involved in glutamatergic neurotransmission. Previous studies in neuropsychiatric disorders associated with the dysregulation of glutamatergic neurotransmission, such as schizophrenia, seizure disorders, and amyotrophic lateral sclerosis (ALS), have revealed region-specific alterations in the levels of NAAG and in the activity of NAALADase. To establish better the cellular localization of these and related parameters in human brain, we have examined their alterations in two well-characterized selective neurodengenerative disorders, Huntington Disease (HD) and Alzheimer Disease (AD). Brain regions from postmortem controls and HD- or AD-affected individuals were assayed to determine the activity of NAALADase as well as the levels of NAAG, N-acetylaspartate (NAA), and several amino acids. The relationships between changes in these neurochemical parameters and changes in neuronal and glial cell density were determined. The present report demonstrates that the decreases in the levels of NAAG and NAA and in the activity of NAALADase in AD and HD brain correlate primarily with neuronal loss. By inference, the results suggest that NAAG and NAA have primarily a neuronal localization in human brain and that there is a close relationship between NAAG and the dipeptidase NAALADase in populations of affected neurons.
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PMID:N-acetylaspartylglutamate, N-acetylaspartate, and N-acetylated alpha-linked acidic dipeptidase in human brain and their alterations in Huntington and Alzheimer's diseases. 937 25

Focal brain damage occurring early in development can have widespread repercussions throughout the developing brain. In living adult rhesus monkeys, we studied the long-term effects of early mesial temporo-limbic (MTL) lesions on prefrontal cortex (PFC) neurons using proton magnetic resonance spectroscopic imaging (1H-MRSI), an in vivo neurochemical assay technique for measuring signals from metabolites such as N-acetyl-aspartate (NAA, a neuronal marker), choline-containing compounds (CHO) and creatine + phosphocreatine (CRE). Six monkeys (NL) had undergone surgical ablation of MTL structures within 3 weeks of birth, six monkeys received the same lesion at approximately 5 years of age and six monkeys were normal controls. We found significant bilateral reductions of NAA relative signals exclusively in the PFC of the NL group in comparison with either of the other groups. Our results indicate that neonatal MTL damage specifically affects PFC neurons of adult monkeys as indicated by a reduction of NAA. The basis of this effect involves developmental processes as implicated by two arguments: analogous damage during adulthood does not have the same effect; NAA in the healthy brain increases during development. This finding may have implications for understanding developmental aspects of prefrontal-temporolimbic connectivity, and the reduction of NAA levels observed in prefrontal cortex of patients with schizophrenia.
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PMID:Altered development of prefrontal neurons in rhesus monkeys with neonatal mesial temporo-limbic lesions: a proton magnetic resonance spectroscopic imaging study. 940 38

1. Studies of first-degree relatives of persons with schizophrenia provide an opportunity to characterize risk factors for the development of this illness. In this report the authors will provide preliminary data from an ongoing study of neurobiological alterations in the offspring of schizophrenia patients. 2. A series of offspring of schizophrenic patients (OS) were compared with age and sex matched healthy controls (HC) without psychiatric history in first degree relatives on psychiatric, volumetric Magnetic Resonance Imaging (MRI) of whole brain and proton Magnetic Resonance Spectroscopy (1H MRS) evaluations of the ventral prefrontal cortex. 3. Compared with HC group, high risk subjects had reduced left amygdala volume, enlarged third ventricular volume, and smaller overall brain volume. 4. 1H MRS studies showed a trend for decreased NAA/choline ratios in the anterior cingulate region in the OS group as compared to HC subjects. 5. Follow-up studies of these subjects are needed to confirm the predictive value of these measures for future emergence of schizophrenia in subjects at risk for this illness.
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PMID:Magnetic resonance imaging and spectroscopy in offspring at risk for schizophrenia: preliminary studies. 946 92

Cerebral 1H MR spectra were recorded in 13 children and adolescents with schizophrenia and 12 healthy children and adolescents. Stimulated echo acquisition mode (STEAM) sequence was used to localize an 8-ml voxel bilaterally in the frontal gray matter. The frontal gray matter metabolite ratios for NAA/Cr, Ch/Cr, Glx/Cr, and mI/Cr in schizophrenic children and adolescents were 1.08 +/- .28, .64 +/- .23, 1.09 +/- .30, and .60 +/- .24, respectively. In comparison, these ratios were 1.59 +/- .35, .74 +/- .27, 1.23 +/- .36, and .58 +/- .29 in healthy children and adolescents. Decrease in the frontal lobe NAA/Cr of schizophrenic children and adolescents was statistically significant (P < .001). In contrast, the MR spectra localized bilaterally in the occipital gray matter (8 ml) showed no significant changes between the patients and the controls. In the occipital gray matter, the metabolite ratios were 1.21 +/- .26,.52 +/- .08, 1.00 +/- .11, and.55 +/- .12 inpatients versus 1.30 +/- .23, .45 +/- .10, 1.15 +/- .20, and .48 +/- .19 in controls. Our preliminary finding of reduced NAA/Cr ratio in the frontal gray matter is consistent with the neurodevelopmental models emphasizing dysfunction of frontal lobe areas in patients with schizophrenia.
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PMID:Preliminary study of frontal lobe 1H MR spectroscopy in childhood-onset schizophrenia. 970 85

Magnetic resonance spectroscopy (MRS), an application of the methods of nuclear magnetic resonance (NMR), is a functional imaging modality that provides a view of localized biochemistry in vivo. A number of studies applying MRS to the neurochemistry of schizophrenia have been reported, which encompass a range of patient populations, states of medication, anatomic regions, nuclear species, and MRS techniques. A brief review of the history and methodology of NMR and MRS is presented. Comparison is made of MRS capabilities with other functional imaging modalities. Aspects of the neurochemistry of schizophrenia relevant to MRS studies are reviewed, as are the reported MRS studies involving patients with schizophrenia. Areas of consistent findings include decreased phosphomonoesters and increased phosphodiesters in frontal lobes, and decreases in the putative neuronal cell marker, N-acetylaspartate, in temporal lobes. Studies of neurotransmitters such as glutamate, gamma-aminobutyric acid, and glutamine have generated inconsistent results. New insights into alterations in neurochemistry in schizophrenia have been provided by MRS. Studies of neurotransmitters have future potential with improvements in field strength and in spectral editing techniques. MRS has the potential to measure brain medication levels and simultaneous effects on neurochemistry. MRS may assist in characterizing high-risk populations, and ultimately guide medication use.
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PMID:In vivo neurochemistry of the brain in schizophrenia as revealed by magnetic resonance spectroscopy. 977 67


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