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)

Schizophrenia is a disorder with an unclear pathophysiology, despite numerous attempts to elucidate its etiology. We have employed proton magnetic resonance spectroscopy in vivo to explore the neurochemistry of several brain regions (left frontal and temporal cortices, left basal ganglia, and left and right thalamus) in patients with schizophrenia and in normal control subjects. We have also examined patients in different medication states. A trend toward a decreased level of inositol/creatine was found in the left temporal lobe of patients with schizophrenia, as was a trend toward a reduced level of N-acetylaspartate/creatine in the left thalamus of patients. In schizophrenic patients treated with atypical antipsychotics, decreased levels of choline were found in the left basal ganglia, while increased levels of N-acetylaspartate were found in the left frontal cortex. These results suggest altered metabolism in patients with schizophrenia, and imply that further study is needed to clarify the effects of the more recently available antipsychotics.
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PMID:Regional proton magnetic resonance spectroscopy in schizophrenia and exploration of drug effect. 981 36

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

Magnetic resonance spectroscopy (MRS) is a non-invasive functional imaging technique that can measure various brain tissue metabolites such as N-acetylaspartate (NAA), choline (Cho), creatine-phosphocreatine (Cr), myo-inositol (mI) and other metabolites. Morphological studies have indicated the pons and cerebellum as possible sites of abnormal functioning in schizophrenic patients. This study examines schizophrenic patients for the presence of abnormalities in proton MRS (1H-MRS) measured metabolites in two regions of the posterior fossa. Twelve schizophrenic patients and eight non-schizophrenic control subjects were studied by measuring the ratios of NAA/Cr, Cho/Cr and mI/Cr from 1H-spectra obtained from the pons and right or left cerebellum using an integrated MRI/MRS protocol. Spectra were obtained from a voxel in the pons and voxels from the left and/or right lateral cerebellum. Data were analyzed in the absorption mode and fitted to Lorentzian lineshapes using a Marquart algorithm. Significantly lower NAA/Cr ratios were found in the pons of schizophrenic patients than in the control subjects, but not in the cerebellum. This study is the first to measure brain tissue metabolites using 1H-MRS in the pons and cerebellum of schizophrenic patients. Significant alterations of 1H-MRS metabolites may suggest the involvement of the posterior fossa as a part of the pathological substrate underlying schizophrenia.
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PMID:Single-voxel proton magnetic resonance spectroscopy of the pons and cerebellum in patients with schizophrenia: a preliminary study. 987 Apr 14

Quantitative proton MR spectroscopy (MRS) and proton-decoupled phosphorus MRS were applied in the parietal cortex of 13 schizophrenic subjects (11 drug-treated and 2 neuroleptic-naive) and 15 normal control subjects. Significantly increased concentrations of glycerophosphorylcholine (1.18 +/- 0.16 vs. 0.93 +/- 0.14 mmol/kg brain; p < 0.001), glycerophosphoethanolomine (0.70 +/- 0.19 vs. 0.59 +/- 0.07 mmol/kg; p < 0.04), and phosphocreatine (3.73 +/- 0.39 vs. 3.41 +/- 0.13 mmol/kg; p < 0.007), but no differences in N-acetylaspartate, total creatine, or myo-inositol, were determined in treated schizophrenic subjects. Identical abnormalities were found in two neuroleptic-naive patients. These results provide new evidence of disordered cerebral membrane and high energy phosphate metabolism in schizophrenia.
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PMID:Quantitative proton-decoupled 31P MRS of the schizophrenic brain in vivo. 1009 36

Quantitative magnetic resonance imaging (MRI) can measure total gray matter volume but cannot discriminate between neurons and glia. Proton magnetic resonance spectroscopic imaging (1H MRSI) measures N-acetylaspartate (NAA) which is a selective marker of neuronal loss or neuronal dysfunction. The objective of this study was to obtain quantitative measures of hippocampal volume and hippocampal NAA to determine if there was evidence for hippocampal neuronal dysfunction or neuronal loss in schizophrenia. Quantitative MRI and 1H MRSI was performed on the right and left hippocampal regions in 23 chronic schizophrenic patients and 18 control subjects. Relative to the control group, the patients with schizophrenia demonstrated no change in hippocampal volumes bilaterally, but significantly decreased NAA in the hippocampal regions bilaterally. There was also no correlation between hippocampal volumes and NAA in either the schizophrenics or controls. These findings suggest that: (1) hippocampal NAA may be a more sensitive measure of neuronal loss than volumetric measurements; and (2) reduced hippocampal NAA may be measuring neuronal dysfunction or damage rather than neuronal loss in this sample of schizophrenics.
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PMID:Reduced hippocampal N-acetylaspartate without volume loss in schizophrenia. 1040 93

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

Schizophrenia has been linked to abnormal dopamine function, recently to excessive amphetamine-induced release of striatal dopamine, and also to pathology of prefrontal cortical neurons. It has been hypothesized that prefrontal pathology is a primary condition that leads to dopamine dysregulation. We evaluated in vivo the relationship between neuronal integrity in dorsolateral prefrontal cortex, assessed as N-acetylaspartate (NAA) relative concentrations measured with proton magnetic resonance spectroscopic imaging, and amphetamine-induced release of striatal dopamine, assessed with 11C-raclopride Positron Emission Tomography (PET) in patients with schizophrenia and in healthy subjects. In the patients, NAA measures in dorsolateral prefrontal cortex selectively predicted striatal displacement of 11C-raclopride after amphetamine infusions (rho = -0.76, p < .02). In contrast, NAA measures in other cortical regions and in healthy subjects did not show any correlation. These results support the hypothesis that in schizophrenia neuronal pathology of dorsolateral prefrontal cortex is directly related to abnormal subcortical dopamine function.
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PMID:The relationship between dorsolateral prefrontal neuronal N-acetylaspartate and evoked release of striatal dopamine in schizophrenia. 1064 25

Brain imaging studies have indicated that the medial temporal lobe functions aberrantly in schizophrenic patients. Both diagnostic subtype and gender may affect functional and morphologic abnormalities in this region. We investigated subtype- and gender-associated differences in metabolites in the left medial temporal lobe in 40 medicated schizophrenic patients by proton magnetic resonance spectroscopy and compared findings with those in 40 healthy control subjects. Peaks corresponding to N-acetylaspartate (NAA), choline-containing compounds (Cho), creatine-phosphocreatine (Cr), and inositol were measured. Schizophrenic patients showed a decrease in the NAA/Cr ratio in the left medial temporal lobe, and patients with the disorganized subtype of illness showed significantly lower NAA/Cr and Cho/Cr ratios than those with paranoid schizophrenia. The NAA/Cr ratio in patients with the undifferentiated subtype also was significantly lower than in the paranoid subtype. No significant associations were observed between metabolite ratios and clinical symptom scores, age at onset of illness, or gender. These findings suggest that patients with the disorganized and undifferentiated subtypes have greater impairments in neuronal integrity or function in the left medial temporal lobe than patients with other subtypes of schizophrenia.
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PMID:Subtype-associated metabolite differences in the temporal lobe in schizophrenia detected by proton magnetic resonance spectroscopy. 1068 59

In vivo proton magnetic resonance spectroscopy (1H MRS) has been utilized by neuroimaging laboratories in recent years to reliably measure compounds such as N-acetylaspartate (NAA), choline (Cho), creatine (Cr), and to a lesser extent glutamate and glutamine in the human brain. To date, the most consistently replicated findings in schizophrenia are reduced NAA measures in the hippocampal regions. Since NAA is thought to be a neuronal/axonal marker and a measure of neuronal/axonal integrity, hippocampal NAA reductions have been interpreted as strong evidence for neuronal/axonal loss or dysfunction in this brain region. The evidence for neuronal loss or dysfunction based on NAA is less consistent for the frontal cortex and white matter, temporal cortex, basal ganglia, cingulate region, and thalamus in schizophrenia. Furthermore, there are no consistently replicated findings for choline or creatine alterations in any of the brain regions examined in schizophrenia. Finally, significant technical difficulties make reliable measurement of glutamine and glutamate problematic at the present time.
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PMID:Proton magnetic resonance spectroscopy of the human brain in schizophrenia. 1071 51

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


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