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)

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

Involvement of the prefrontal cortex in schizophrenia has been implicated by neuropsychological, as well as neuropathological and imaging studies. Reductions of N-acetylaspartate (NAA), an in vivo marker of neuronal integrity, have repeatedly been detected in the frontal lobes of patients with schizophrenia by proton magnetic resonance spectroscopy (1H-MRS). In chronic medicated patients, a positive correlation between NAA levels of the prefrontal cortex and cognitive functioning has been observed, but to date, there have been no studies in first-episode neuroleptic-naive patients. In this study, single-voxel 1H-MRS was used to investigate neuronal function of the dorsolateral prefrontal cortex in 15 first-episode and 20 chronic schizophrenic patients. Outcomes were compared to 20 age-matched healthy controls to assess the relationship between prefrontal metabolism and neuropsychological performance. Patients with chronic schizophrenia had significant reductions of NAA, glutamate/glutamine, and choline levels compared to first-episode patients and healthy controls. Furthermore, creatine and phosphocreatine were significantly reduced in both patient groups compared to healthy controls. In the neuropsychological tests, chronic schizophrenic patients performed significantly poorer in the Auditory Verbal Learning Task (AVLT) compared to first-episode patients. In both patient groups, NAA levels of the left frontal lobe significantly correlated with performances in verbal learning and memory. These results corroborate data from recent structural and spectroscopic imaging studies of the frontal lobes in schizophrenia, in which cortical gray matter reductions after onset of symptoms as well as reduced levels of NAA in chronic, but not in first-episode schizophrenic patients have been reported.
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PMID:Cognitive impairment and in vivo metabolites in first-episode neuroleptic-naive and chronic medicated schizophrenic patients: a proton magnetic resonance spectroscopy study. 1694 99

Recent studies have provided evidence for neuronal and oligodendrocyte-related abnormalities being associated with schizophrenia. However, the functional interplay and causal relationship between these two abnormalities is poorly understood. In this report, we provide data that identify myelin and fatty-acid biosynthesis dysfunction in schizophrenia based on post-mortem brain studies (prefrontal cortex) utilizing parallel metabolic and transcriptomics investigations. We detected a significant up-regulation of N-acetylaspartate (NAA) by HPLC analysis. Microarray and Q-PCR investigations revealed mRNA abnormalities for several enzymes involved in NAA metabolism. Additionally, glutamatergic neurotransmission components were also found to be affected. Our results suggest that, apart from the previously reported alterations in myelin-related protein synthesis, myelin synthesis itself may be directly affected in schizophrenia as indicated by changes in key enzymes involved in NAA metabolism. A decrease in NAA catabolism in oligodendrocytes would severely reduce acetate levels required to produce myelin lipids and may subsequently affect glutamatergic neurotransmission.
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PMID:Further evidence for altered myelin biosynthesis and glutamatergic dysfunction in schizophrenia. 1729 71

There is an accumulation of evidence for abnormalities in schizophrenia of both the major neurotransmitter systems of the brain - those of GABA (gamma-aminobutyric acid) and glutamate. Initial studies have found deficits in the putative neuronal marker, N-acetylaspartate, in a number of brain regions in schizophrenia. The animal models have provided some interesting correlates and discrepancies with these findings. The deficit in inhibitory interneurons within structures implicated in schizophrenic symptomatology may well have direct functional relevance, and can be induced by animal models of the disease such as subchronic phencyclidine administration or social isolation. Their association with these animal models suggests an environmental involvement. A loss of glutamatergic function in schizophrenia is supported by decreases in markers for the neuronal glutamate transporter in striatal structures that receive cortical glutamatergic projections. Deficits in the VGluT1 (vesicular glutamate transporter-1) in both striatal and hippocampal regions support this observation, and the association of VGluT1 density with a genetic risk factor for schizophrenia points to genetic influences on these glutamatergic deficits. Further studies differentiating neuronal loss from diminished activity and improved models allowing us to determine the temporal and causal relationships between GABAergic and glutamatergic deficits will lead to a better understanding of the processes underlying the neuronal pathology of schizophrenia.
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PMID:The neuronal pathology of schizophrenia: molecules and mechanisms. 1737 Dec 93

The anterior cingulate region is thought to be dysfunctional in schizophrenia, but whether this is the result of reduced neuronal integrity or changes in neurotransmitter systems remains an issue of debate. Fifteen male patients with schizophrenia and 14 male controls were assessed using proton magnetic resonance spectroscopy, with regions of interest placed in the right and left dorsal and rostral cingulate. The metabolites of interest were N-acetylaspartate (NAA), a putative neuronal marker, and glutamate + glutamine (Glx), which may index synapse number. Schizophrenia patients had lower NAA concentrations throughout the dorsal and rostral portions of the anterior cingulate and in both hemispheres, but showed no changes in Glx. Anterior cingulate involvement in schizophrenia is likely to be a result of neuronal loss or dysfunction.
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PMID:Evidence for neuronal dysfunction in the anterior cingulate of patients with schizophrenia: a proton magnetic resonance spectroscopy study at 3 T. 1757 88

The author reviews literature on the topic of the morphological and neurochemical changes in the brain in schizophrenia which is connected with the influence of the antipsychotics, both I and II generation. The most replicated findings in schizophrenia are: an increase of basal ganglia volume and decrease of grey matter in different regions (after typical neuroleptics). These phenomena are not stated after atypical neuroleptics. If, especially in the first period of the disease the progression of the morphological changes in the brain in schizophrenia,, can be observed, the atypical neuroleptics could limit that process and classical neuroleptics - rather not. The atypics may also act neuroprotectively on the brain tissue. This action can also be observed in the results of proton magnetic resonance spectroscopy. The increase of N-acetylaspartate (NAA) levels in different brain regions was observed after treatment with atypical medication. NAA is recognised as the marker of neurons viability and function. The author discusses the possible mechanisms of neuroleptic action on the brain in schizophrenia and future research directions.
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PMID:[First and second generation antipsychotics and morphological and neurochemical brain changes in schizophrenia. Review of magnetic resonance imaging and proton spectroscopy findings]. 1790 49

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

Metabolic brain abnormalities, as demonstrated by (1)H-magnetic resonance spectroscopy, are common occurrences in adult schizophrenia. As mice share important biochemical and genomic similarities with humans, we tested whether brain metabolic abnormalities also occur in a transgenic mouse model of schizophrenia. In vivo(1)H-magnetic resonance spectroscopy at 4.7T of the chakragati mouse brain revealed abnormalities in relative levels of choline and N-acetylaspartate compounds. These results are consistent with a prior proposal that deficits in metabolite ratios may be common features of psychotic disorders. Thus, chakragati mice recapitulate certain aspects of the human disease phenotype and further support the utility of this animal model for understanding causal factors underlying uniquely human brain diseases.
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PMID:Magnetic resonance imaging and spectroscopy in a mouse model of schizophrenia. 1835 31

There have been many theories about and computational models of the schizophrenic disease state. Brain imaging techniques have suggested that abnormalities of the thalamus may contribute to the pathophysiology of schizophrenia. Several studies have found the thalamus to be altered in schizophrenia, and the thalamus has connections with other brain structures implicated in the disorder. This paper describes an experiment examining thalamic levels of the metabolite N-acetylaspartate (NAA), taken from schizophrenics and controls using in vivo proton magnetic resonance spectroscopic imaging. Automatic relevance determination was performed on neural networks trained on this data, identifying NAA group differences in the pulvinar and mediodorsal nucleus, underscoring the importance of examining thalamic subregions in schizophrenia.
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PMID:Automatic relevance determination for identifying thalamic regions implicated in schizophrenia. 1854 7


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