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)

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

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

Prostate-specific membrane antigen (PSMA) is a 100 kDa type II transmembrane protein with folate hydrolase and NAALAdase activity. PSMA is highly expressed in prostate cancer and the vasculature of most solid tumors, and is currently the target of a number of diagnostic and therapeutic strategies. PSMA is also expressed in the brain, and is involved in conversion of the major neurotransmitter NAAG (N-acetyl-aspartyl glutamate) to NAA and free glutamate, the levels of which are disrupted in several neurological disorders including multiple sclerosis, amyotrophic lateral sclerosis, Alzheimer's disease and schizophrenia. To facilitate analysis of the role of PSMA in carcinoma we have determined the structural organization of the gene. The gene consists of 19 exons spanning approximately 60 kb of genomic DNA. A 1244 nt portion of the 5' region of the PSMA gene was able to drive the firefly luciferase reporter gene in prostate but not breast-derived cell lines. We have mapped the gene encoding PSMA to 11p11-p12, however a gene homologous, but not identical, to PSMA exists on chromosome 11q14. Analysis of sequence differences between non-coding regions of the two genes suggests duplication and divergence occurred 22 million years ago.
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PMID:Mapping, genomic organization and promoter analysis of the human prostate-specific membrane antigen gene. 983 72

Neurochemical brain imaging methods developed over the past 20 years offer significant promise for elucidating the biochemical underpinnings of schizophrenia. The two general methodologies used for these studies have been: 1) radiotracer imaging: PET (positron emission tomography) and SPECT (single photon emission computed tomography); and 2) NMR (nuclear magnetic resonance) imaging: fMRI (functional magnetic resonance imaging) and MRS (magnetic resonance spectroscopy). Despite conflicting findings, striatal D2 receptor density may be elevated in some, but not all patients. Elevated synthesis, and increased release of dopamine after amphetamine challenge have also been reported. Imaging of cortical 5-HT2A receptors suggests that this system is unaffected, in conflict with findings of postmortem studies. Although prior postmortem studies suggested an increase in cortical GABAA receptors, three SPECT studies have found no significant changes. MRS studies have shown decreased levels of NAA (N-acetyl-aspartate) moieties in hippocampus and frontal cortex of schizophrenic patients, which is consistent with the reported loss of neurons and neuropil in postmortem brains. In conclusion, developments in radiotracer and NMR imaging have provided promising leads to the biochemical abnormalities associated with schizophrenia. Future significant understanding is likely to occur with the development of new probes and enhanced instrument technology, when applied with an appreciation of the heterogeneity of the disorder and the need for careful clinical assessment of patients.
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PMID:Neurochemical brain imaging investigations of schizophrenia. 1047 14

The authors performed a MRSI study of the anterior cingulate gyrus in 19 schizophrenic patients under stable medication and 16 controls in order to corroborate previous findings of reduced NAA in the anterior cingulate region in schizophrenia. Furthermore, correlations between NAA in the anterior cingulate gyrus and age or illness duration have been determined. A decreased NAA signal was found in the anterior cingulate gyrus of patients compared to controls. Subdividing the patient group into two groups depending on medication revealed that the group of patients receiving a typical neuroleptic medication showed a lower mean NAA in comparison to the group of patients receiving atypical antipsychotic drugs. No significant group differences in the creatine and phosphocreatine signal or the signal from choline-containing compounds were found. The NAA signal significantly correlated with age, and therefore, individual NAA values were corrected for the age effect found in the control group. The age-corrected NAA signal in schizophrenia correlated significantly with the duration of illness. The detected correlations of NAA decrease with age and illness duration are consistent with recent imaging studies where progressing cortical atrophy in schizophrenia was found. Further studies will be needed to corroborate a possible favorable effect of atypical antipsychotics on the NAA signal.
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PMID:Effects of age, medication, and illness duration on the N-acetyl aspartate signal of the anterior cingulate region in schizophrenia. 1072 16

To determine if there was evidence for altered neuronal integrity in the cerebellar vermis of patients with schizophrenia, the authors measured N-acetyl-aspartate (NAA, a putative neuronal/axonal marker) using in vivo proton magnetic resonance spectroscopic imaging (1H-MRSI) in 20 chronically medicated male patients with schizophrenia and 15 male comparison subjects. Relative contributions of cerebrospinal fluid, gray matter, and white matter to each MRSI voxel were determined using an MRI tissue segmentation technique. The percentage of tissue was used as a co-variate to determine the extent to which tissue composition contributed to NAA differences. Schizophrenic patients showed significantly decreased NAA and creatine in the anterior cerebellar vermis, independent of differences in voxel tissue composition. Cerebellar NAA levels in control subjects were also significantly correlated with the amount of cerebellar gray matter enclosed in the MRSI voxels, but not in the schizophrenic group. There was no association between cerebellar NAA measures and duration of illness or neuroleptic dose in chlorpromazine equivalents. Reduced NAA in the anterior cerebellar vermis of male patients with schizophrenia supports the hypothesis that cerebellar dysfunction contributes to the pathophysiology of schizophrenia. Furthermore, the lack of a significant correlation between NAA and the amount of cerebellar gray matter in MRSI voxels in the schizophrenic group suggests that NAA levels in both cerebellar gray and white matter are similar in schizophrenic patients, and are presumed to be the result of reduced NAA concentration in the cerebellar gray matter.
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PMID:Evidence for altered cerebellar vermis neuronal integrity in schizophrenia. 1156 29

Previous studies in animals suggested that neonatal lesions of the ventral hippocampus disrupt development of prefrontal cortex and its regulation of dopaminergic activity. In the present study, we assayed an in vivo chemical marker of neuronal integrity (proton magnetic resonance spectroscopy signal of N-acetylaspartate, NAA) in prefrontal cortex and striatum of rats with neonatal excitotoxic lesions of the ventral hippocampus. We also measured in post-mortem tissue expression of EAAC1 mRNA, a molecular marker of intrinsic neurons. In the cohort studied at juvenile age and again at young adulthood [postnatal day (PD) 37 and 71], we found selective reductions of NAA in the prefrontal cortex only at PD 71. Emergence of neuronal pathology was temporally associated with emergence of amphetamine-induced hyperlocomotion. Reduced prefrontal NAA was confirmed in the second cohort studied at an older age (PD 120). Expression of EAAC1 mRNA was significantly reduced in prefrontal cortex of the lesioned rats. No changes in NAA were found in the striatum in either cohort and cortical area size was not changed. These results suggest that early ventral hippocampal lesions produce developmental neuronal pathology in prefrontal cortex that is temporally associated with dysregulation of dopamine behaviors and is reminiscent of the temporal profile of the onset of schizophrenia.
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PMID:Reduced N-acetylaspartate in prefrontal cortex of adult rats with neonatal hippocampal damage. 1218 97


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