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)

Reduced frontal N-acetylaspartate (NAA) has been repeatedly found in chronic schizophrenia and suggests neuronal loss or dysfunction. However, the potential confounding effect of antipsychotic drugs on NAA has not been resolved. The few studies of antipsychotic-nai;ve patients are inconclusive. A recent report suggests that antipsychotic drugs may increase NAA in the dorsolateral prefrontal cortex (DLPFC). We studied 10 minimally treated (less than 3 weeks lifetime exposure) schizophrenia patients and 10 normal controls with single-voxel proton magnetic resonance spectroscopy (1H-MRS) of the left frontal and occipital lobes. Concentrations of NAA, Cho, and Cre were determined and corrected for the proportion of cerebrospinal fluid (CSF) in the voxel. Patients were treated in a randomized-controlled double-blind design with either haloperidol or quetiapine. 1H-MRS was repeated within a year. There were no differences in frontal or occipital NAA between patients and controls at baseline. However, frontal NAA was reduced in the schizophrenia group within the first year of treatment. Patients had a clear clinical response to treatment but changes in frontal NAA were not correlated with symptom improvement. The well-described reduced frontal NAA in schizophrenia may not be a trait of the illness but may represent medication effect or progression of the disease.
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PMID:Longitudinal follow-up of neurochemical changes during the first year of antipsychotic treatment in schizophrenia patients with minimal previous medication exposure. 1240 72

Abnormal phospholipid metabolisms may play important roles in the pathophysiology of schizophrenia. Phosphorus magnetic resonance spectroscopy (31P-MRS) offers a new method for studying phosphorus-related metabolism in vivo. A decrease in the level of phosphomonoesters (PME) and an increase in the level of phosphodiesters (PDE) has been demonstrated in the prefrontal lobe of neuroleptic-naive schizophrenic patients. Most of the studies in medicated schizophrenic patients have shown decreased PME and/or increased PDE. The decreased PME in the frontal lobe appears to be associated with negative symptoms and poor working memory performance. 1H-decoupled 31P-MRS revealed a reduction in the phosphocholine element of PME and an elevation in the mobile phospholipids of PDE in the prefrontal region of medicated schizophrenic patients. PDE were elevated in the temporal lobes of neuroleptic-naive schizophrenic patients, and this increase was partially normalized by haloperidol administration. Data about the temporal lobes of medicated schizophrenic patients have not been consistent. Except for the reduction in the adenosine triphosphate (ATP) in the basal ganglia and the correlation between the increase in the frontal lobe phosphocreatine (PCr) and negative symptomatology, data related to changes in high-energy phosphates are contradictory. No consensus on the effect of neuroleptics on phosphorus metabolites has been achieved. Methodological problems inherent in 31P-MRS may have contributed to the confusion in understanding available data. Future directions of MRS studies are suggested in the last section of the paper.
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PMID:Neurochemical investigation of the schizophrenic brain by in vivo phosphorus magnetic resonance spectroscopy. 1258 88

In vivo (31)P magnetic resonance spectroscopy ((31)P MRS) studies have shown abnormal membrane phospholipid metabolism in the prefrontal cortex (PF) in the early course of schizophrenia. It is unclear, however, whether these alterations also represent premorbid risk indicators in schizophrenia. In this paper, we report in vivo (31)P MRS data on children and adolescents at high risk (HR) for schizophrenia. In vivo (31)P MRS studies of the PF were conducted on 16 nonpsychotic HR offspring of parents with schizophrenia or schizoaffective disorder, and 37 age-matched healthy comparison (HC) subjects. While 11 of the HR subjects had evidence of Axis I psychopathology (HR-P), five HR subjects had none (HR-NP). We quantified the freely mobile phosphomonoester (PME) and phosphodiester (PDE) levels reflecting membrane phospholipid precursors and breakdown products, respectively, and the relatively broad signal underlying PDE and PME peaks, comprised of less mobile molecules with PDE and PME moieties (eg, synaptic vesicles and phosphorylated proteins). Compared to HC subjects, HR subjects had reductions in freely mobile PME; the differences were accounted for mainly by the HR-P subjects. Additionally, HR-P subjects showed increases in the broad signal underlying the PME and PDE peaks in the PF. To conclude, these data demonstrate new evidence for decreased synthesis of membrane phospholipids and possibly altered content or the molecular environment of synaptic vesicles and/or phosphoproteins in the PF of young offspring at risk for schizophrenia. Follow-up studies are needed to examine the predictive value of these measures for future emergence of schizophrenia in at-risk individuals.
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PMID:Prefrontal membrane phospholipid metabolism of child and adolescent offspring at risk for schizophrenia or schizoaffective disorder: an in vivo 31P MRS study. 1266 Aug 4

Based on a previous report [9] on alterations of membrane phosphorus metabolism in asymptomatic family members of schizophrenic patients, the aim of the present study was to extend and improve the evaluation and data processing of (31)P spectroscopic data obtained from a larger study population by including an analysis of the broad spectral component (BC) of membrane phospholipids (PL). Eighteen children and siblings of patients with schizophrenia and a gender- and age-matched control group of 18 healthy subjects without familial schizophrenia were investigated with phosphorus magnetic resonance spectroscopy ((31)P-MRS) by using image selected in vivo spectroscopy (ISIS) in the dorsolateral prefrontal regions (DLPFR) of the brain. Spectral analysis was performed by using both the full and truncated FID to estimate metabolic peak ratios of different (31)P metabolites and the intensity and linewidth of the broad component. A significantly higher PDE level (p<0.01) and increased linewidth of the PDE components were observed for the high-risk group compared with the control group (p=0.02). No significant differences were observed for PME as well as for other (31)P-metabolites. No differences were observed between the left and right hemispheres for different normalised (31)P-metabolic levels. Decreased intensities (p=0.03) and smaller linewidths (p=0.01) were obtained for the broad component in the high-risk group. Impairments of membrane metabolism that are typical for schizophrenic patients are partially observed in adolescent asymptomatic family members of schizophrenics, including increased levels of low molecular PDE compounds indicating increased membrane degradation processes, no changes for PME, and decreased intensities and linewidths of the BC indicating changes in the composition and fluidity of membrane phospholipids. Despite limitations to completely suppress fast-relaxing components by dismissing initial FID data points, the spectroscopic results indicate additional changes in the membrane metabolism of high-risk subjects beyond changes of synthesis and degradation.
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PMID:31P-MR spectroscopy in children and adolescents with a familial risk of schizophrenia. 1266 15

Single voxel proton magnetic resonance spectroscopy (1H MRS) was used to study the metabolites N-acetylaspartate (NAA), choline (CHO), and myo-inositol (ml) in order to test a neurodegenerative hypothesis in schizophrenia (decrease of NAA, increase of CHO, and increase of ml) and a cerebral asymmetry of these metabolites. 1H MRS was performed in 17 schizophrenia patients and 14 healthy subjects in three cerebral areas highly involved in the pathophysiology of schizophrenia (the prefrontal cortex, the thalamus, and the hippocampus). The ratio amplitudes between metabolites and creatine plus phosphocreatine (Cr) were determined. No difference in the metabolites existed between patients and healthy subjects. However, relationships were noted between NAA/Cr and age in the thalami of the schizophrenia patients (r = -0.37; p = 0.14) and healthy subjects (r = -0.52; p = 0.05). A significant correlation was observed between NAA/Cr and age of onset of illness in the hippocampi of schizophrenia patients (r = -0.59; p < 0.05). Moreover, NAA/Cr was lower in the right than in the left prefrontal cortex in both schizophrenia patients and healthy subjects. There was no relationship between the metabolites and duration of illness or dose of antipsychotics. These findings might suggest a neurodegenerative process in the hippocampi of schizophrenia patients with late onset of illness, and the NAA/Cr ratio could be a marker of aging in the thalami.
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PMID:Proton magnetic resonance spectroscopy (1H MRS) in schizophrenia: investigation of the right and left hippocampus, thalamus, and prefrontal cortex. 1269 38

Extrapyramidal side-effects (EPS), the most frequent and severe side-effects of antipsychotics, sometimes become irreversible and cause severe psychosocial disturbance in patients with schizophrenia. However, the neurobiological basis of EPS has not yet been elucidated. In this study, neurochemical correlates of EPS were examined by 1H-MR spectroscopy (1H-MRS). Sixteen medicated patients with schizophrenia and 15 age-, gender- and parental-socioeconomic-status-matched normal controls were examined using single-voxel 1H-MRS. Absolute concentrations of N-acetyl aspartate (NAA), choline-containing compounds (Cho), creatine/phosphocreatine, myo-inositol, and Glx (glutamate and glutamine) in the left putamen were evaluated. The patient group showed mild EPS and no significant metabolic abnormalities in this region. The more severe drug-induced parkinsonism assessed by the Simpson-Angus Scale, however, significantly correlated with the higher Cho concentration and tended to be correlated with the higher NAA concentration in the patient group. These results suggest a potential of 1H-MRS as a non-invasive monitoring method of neurobiological correlates of EPS associated with neuroleptic treatments in patients with schizophrenia.
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PMID:Drug-induced parkinsonism in relation to choline-containing compounds measured by 1H-MR spectroscopy in putamen of chronically medicated patients with schizophrenia. 1460 50

Phosphorus Magnetic Resonance Spectroscopy (31P-MRS) has been utilized to study energy, carbohydrate, and phospholipid metabolism in vitro and in vivo in live tissues non-invasively. Despite its lack of sensitivity, its application has extended to in situ human tissues and organs since proper signal localization was devised. Follow-up of phosphocreatine in neuromuscular diseases and schizophrenia and follow-up of phospholipid-related molecules in tumors are described here to demonstrate the value of 31P-MRS as an imaging technique to determine in vivo markers of disease and in the diagnosis, prognosis, and follow-up of human diseases.
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PMID:In vivo measurement of phosphorous markers of disease. 1509 5

Magnetic resonance spectroscopy is a noninvasive investigative technique for in vivo detection of biochemical changes in neuropsychiatric disorders for which especially proton (1H-MRS) and phosphorus (31P-MRS) magnetic resonance spectroscopy have been used. In this review we explain the principles of MRS and summarize the studies in schizophrenia. A systematic literature review was carried out for 1H-MRS studies investigating schizophrenic patients compared to controls. The inconsistent results in the cited studies may be due to different study population, specific neuroimaging technique, and selected brain regions. Frequent findings are decreased PME and increased PDE concentrations (31P-MRS) linked to altered metabolism of membrane phospholipids and decreased N-acetylaspartate (NAA) or NAA/choline ratio (1H-MRS) linked to neuronal damage in frontal (DLPFC) or temporal regions in patients with schizophrenia. These results contribute to the disturbed frontotemporal-thalamic network assumed in schizophrenia and are supported by additional functional neuroimaging, MRI morphometry, and neuropsychological evaluation. The combination of the described investigative techniques with MRS in follow-up studies may provide more specific clues for understanding the pathogenesis and disease course in schizophrenia.
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PMID:[Magnetic resonance spectroscopy in schizophrenia. Possibilities and limitations]. 1564 3

Proton magnetic resonance spectroscopy (1H-MRS) studies of schizophrenia suggest an effect of the disease or of antipsychotic medications on brain N-acetyl aspartate (NAA), a marker of neuronal viability. We studied in rat the effect of haloperidol on NAA, glutamate, and glutamine in several brain regions where metabolite reductions have been reported in chronically medicated patients with schizophrenia. Two groups of 16 rats each were treated with haloperidol depo (38 mg/kg/month) and vehicle for 6 months and were killed. Concentrations of metabolites were determined by high-resolution magic angle proton magnetic resonance spectroscopy (HR-MAS 1H-MRS) at 11.7 T in ex-vivo punch biopsies from the following brain regions: medial frontal and cingulate cortex, striatum, nucleus accumbens, dorsal and ventral hippocampus, amygdala, and temporal cortex. Factorial ANOVA of NAA concentrations revealed no significant effect of drug group (F(1,212) = 1.5; p = 0.22) or a group by brain region interaction (F(7,212) = 1.0; p = 0.43). There was a significant main effect of region (F(7,212) = 17.8; p < 0.001) with lower NAA in the striatum. A prolonged exposure to the dopamine D2 receptor blockade effects of haloperidol does not result in changes in NAA, glutamate, glutamine, and other metabolites in the proton spectrum. These results are consistent with the only other two studies of the effect of antipsychotic drugs on NAA in the rat brain. The documented lower NAA in chronically treated schizophrenia patients is most likely not a simple effect of antipsychotic medications.
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PMID:Long-term treatment of rats with haloperidol: lack of an effect on brain N-acetyl aspartate levels. 1613 64

Altered high energy and membrane metabolism, measured with phosphorus magnetic resonance spectroscopy (31P-MRS), has been inconsistently reported in schizophrenic patients in several anatomical brain regions implicated in the pathophysiology of this illness, with little attention to the effects of brain tissue type on the results. Tissue regression analysis correlates brain tissue type to measured metabolite levels, allowing for the extraction of "pure" estimated grey and white matter compartment metabolite levels. We use this tissue analysis technique on a clinical dataset of first episode schizophrenic patients and matched controls to investigate the effect of brain tissue specificity on altered energy and membrane metabolism. In vivo brain spectra from two regions, (a) the fronto-temporal-striatal region and (b) the frontal-lobes, were analyzed from 12 first episode schizophrenic patients and 11 matched controls from a (31)P chemical shift imaging (CSI) study at 4 Tesla (T) field strength. Tissue regression analyses using voxels from each region were performed relating metabolite levels to tissue content, examining phosphorus metabolite levels in grey and white matter compartments. Compared with controls, the first episode schizophrenic patient group showed significantly increased adenosine triphosphate levels (B-ATP) in white matter and decreased B-ATP levels in grey matter in the fronto-temporal-striatal region. No significant metabolite level differences were found in grey or white matter compartments in the frontal cortex. Tissue regression analysis reveals grey and white matter specific aberrations in high-energy phosphates in first episode schizophrenia. Although past studies report inconsistent regional differences in high-energy phosphate levels in schizophrenia, the present analysis suggests more widespread differences that seem to be strongly related to tissue type. Our data suggest that differences in grey and white matter tissue content between past studies may account for some of the variance in the literature.
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PMID:Grey and white matter differences in brain energy metabolism in first episode schizophrenia: 31P-MRS chemical shift imaging at 4 Tesla. 1649 88


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