phosphocreatine and Schizophrenia

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.

Topics: Antipsychotic Agents; Brain; Frontal Lobe; Humans; Magnetic Resonance Spectroscopy; Phosphocreatine; Phospholipids; Phosphoric Diester Hydrolases; Phosphoric Monoester Hydrolases; Schizophrenia; Temporal Lobe

31Phosphorus nuclear magnetic resonance spectroscopy (31P-MRS) has gained much interest in schizophrenia research in the last years, since it allows noninvasive measurement of high energy phosphates and phospholipids of the human brain in vivo. Thus, several studies have reported cerebral metabolic differences between patients and healthy controls as well as on lateralization effects and influences of epidemiological and psychopathological factors. This review gives a survey of the potential of 31P-MRS in schizophrenia research and summarizes and comments on the results of preceding studies. The discussion covers the reduction of phospholipids in patients in the context of the membrane phospholipid hypotheses, the question of an energetic hypometabolism in schizophrenics, and the influence of neuroleptic medication.

Topics: Adenosine Triphosphate; Age Factors; Brain; Brain Chemistry; Controlled Clinical Trials as Topic; Dominance, Cerebral; Humans; Magnetic Resonance Spectroscopy; Phosphates; Phosphocreatine; Phospholipids; Phosphorus Radioisotopes; Schizophrenia; Sex Factors

We reported increased high-energy phosphate metabolism in the basal ganglia of antipsychotic-naïve schizophrenia patients using (31)P Magnetic Resonance Spectroscopy (MRS). These patients were followed up for 1 year and and reassessed using (31)P MRS. Fourteen (8 males) patients with DSM-IV schizophrenia and 14 (11 males) healthy controls underwent (31)P MRS of sub-cortical structures (predominantly basal ganglia) twice (mean+/-S.D. interscan interval 1.15+/-0.17year) on a 1.5T scanner. Total scores on the Positive and Negative Syndrome Scale (PANSS) decreased significantly after treatment in schizophrenia patients. Patients had significantly lower mean PCr/ATP ratios than healthy controls at baseline but not during the follow-up. In patients, there was a significant positive correlation between the magnitude of improvement in PANSS total scores and the extent of change in the PCr/ATP ratio. Findings support the hypothesis that reduction of energy demand or induction of decreased energy-demanding processes might underlie the mechanism of action of antipsychotics in schizophrenia.

Topics: Adenosine Triphosphate; Adult; Analysis of Variance; Antipsychotic Agents; Aspartic Acid; Basal Ganglia; Female; Humans; Longitudinal Studies; Magnetic Resonance Spectroscopy; Male; Phosphocreatine; Phosphorus Isotopes; Psychiatric Status Rating Scales; Radionuclide Imaging; Schizophrenia; Young Adult

In this report, we describe the implementation and application of a fully automated segmentation routine using SPM99 algorithms and MATLAB for clinical Magnetic Resonance Spectroscopic Imaging (MRSI) studies. By segmenting high-resolution 3-D image data and coregistering the results to the spatial localizer slices of a spectroscopy examination, the program offers the possibility to easily calculate segmentation maps for a large variety of MRSI experiments. The segmented data are corrected for the individual point-spread function, slice and VOI profiles for measurement sequences with selective pulses as well as for the chemical shifts of different metabolites. The new method was applied to investigate discrete hippocampal metabolite abnormalities in a small sample of schizophrenic patients in comparison to healthy controls (15 patients, 15 controls). Only after correction was the N-acetyl-aspartate (NAA) signal significantly lower in patients compared to controls. No differences were found for the corrected signals from the creatine/phosphocreatine (Cr) or choline-containing compounds (Ch). These results are in good agreement with neuropathological and previous MR spectroscopy studies of the hippocampus in schizophrenic patients.

Topics: Adult; Algorithms; Aspartic Acid; Choline; Creatine; Female; Hippocampus; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Male; Middle Aged; Phosphocreatine; Schizophrenia

Using proton magnetic resonance spectroscopic imaging (1H-MRSI) we found in a previous study a specific pattern of neuronal pathology in patients with schizophrenia as determined by relative loss of signal from N-acetyl-containing compounds (NAA). The purpose of the present study was to assess the reproducibility of the results of 1H-MRSI both in patients with schizophrenia and in normal controls. We studied twice 10 patients and 10 controls on 2 days separated by, on average, 3 months. Reproducibility was assessed with several statistical procedures including ANOVA, coefficients of variation (CVs) and intra-class correlation coefficients (ICC). Patients showed significant reductions of NAA/creatine-phosphocreatine (CRE) and NAA/choline-containing compounds (CHO) selectively in the hippocampal region (HIPPO) and in the dorsolateral prefrontal cortex (DLPFC) on both experimental days. A repeated measures ANOVA showed no effect of time on metabolite ratios in all subjects. CVs were fairly low (especially for NAA/CRE and CHO/CRE) and did not differ significantly between patients and controls. The ICCs of the ROIs reached statistical significance only in a few instances. The present multislice 1H-MRSI study shows that: (1) patients with schizophrenia, when compared as a group to normal controls, show a consistent 1H-MRSI pattern of group differences, i.e., bilateral reductions of NAA/CRE and NAA/CHO in HIPPO and DLPFC; (2)1H-MRSI data in both patients and controls do not show significant changes over this 90-day period; however, absolute metabolite ratios in individuals show low predictability over this time interval; (3) 1H-MRSI data show relatively low variability (as measured by the CVs) both in patients and normal controls, especially for NAA/CRE and CHO/CRE.

Topics: Acetylation; Adult; Brain Chemistry; Choline; Creatine; Female; Hippocampus; Humans; Magnetic Resonance Imaging; Male; Phosphocreatine; Prefrontal Cortex; Reproducibility of Results; Schizophrenia

In a preliminary study we found decreased phosphodiester (PDE)% values and an increased phosphomonoester (PME)/phosphodiester ratio in the dorsolateral prefrontal region (DLPFR) of 13 chronic schizophrenics vs. 14 controls using 31phosphorus magnetic resonance spectroscopy (31P-MRS). Since these results are in contrast to the findings of other groups, we increased our study group to a total of 50 chronic schizophrenics on stable neuroleptic medication and 36 controls to minimize the possibility of a chance result due to small sample size.. An image-selected in vivo 31P-MRS method on a Philips Gyroscan ACS II scanner working at 1.5 T was used.. We could confirm our earlier findings of decreased PDE% levels in schizophrenics. Additionally, we found phosphocreatine (PCr)% and PCr/adenosine triphosphate (ATP) to be increased in the schizophrenics. While no association between PME% and PDE% with neuroleptic medication was found, ATP% correlated positively and PCr/ATP negatively with the chlorpromazine equivalent dose.. The decreased PDE% levels might be characteristic only for chronic, neuroleptic-treated patients. The finding of altered high-energy phosphate levels can be interpreted as an indication of decreased energy-demanding processes in the DLPFR of the investigated patients compared to controls.

Topics: Adenosine Triphosphate; Adult; Brain Chemistry; Female; Humans; Magnetic Resonance Spectroscopy; Male; Organophosphates; Phosphocreatine; Prefrontal Cortex; Psychiatric Status Rating Scales; Schizophrenia

Shared neurobiological characteristics of patients with schizophrenia and their siblings may represent "intermediate phenotypes" that may more closely reflect the genetic susceptibility underlying this illness. We sought evidence of such phenotypes using magnetic resonance spectroscopy based on previously described regional abnormalities in levels of the neuronal marker N-acetyl-aspartate (NAA) in the hippocampal area and dorsolateral prefrontal cortex of patients with schizophrenia.. We studied 47 schizophrenics, 60 unaffected siblings, and 66 healthy control subjects with long echo time multislice proton magnetic resonance spectroscopic imaging, primarily measuring NAA, creatine plus phosphocreatine (CRE), and choline-containing compounds.. Both patients and their unaffected siblings had significant reductions in hippocampal area NAA/CRE as compared with control subjects. As exploratory analyses, estimates of heritability were performed. Although quantitative correlation of hippocampal NAA between patients and sibs was low (likely reflecting measurement noise), qualitatively defined "low hippocampal NAA/CRE phenotypes" yielded relative risk estimates (lambda s) of between 3.8 and 8.8, suggesting this characteristic is heritable.. Our finding adds to the evidence that hippocampal abnormalities are associated with schizophrenia and may represent a novel biological phenotype for genetic studies of schizophrenia.

Topics: Adult; Aspartic Acid; Biomarkers; Choline; Creatine; Family; Female; Hippocampus; Humans; Magnetic Resonance Imaging; Male; Phenotype; Phosphocreatine; Prefrontal Cortex; Risk; Schizophrenia

Abnormalities in neural activity and cerebral bioenergetics have been observed in schizophrenia (SZ). Further defining energy metabolism anomalies would provide crucial information about molecular mechanisms underlying SZ and may be valuable for developing novel treatment strategies.. To investigate cerebral bioenergetics in SZ via measurement of creatine kinase activity using in vivo 31P magnetization transfer spectroscopy.. Cross-sectional case-control study in the setting of clinical services and a brain imaging center of an academic psychiatric hospital. Twenty-six participants with chronic SZ (including a subgroup diagnosed as having schizoaffective disorder) and 26 age-matched and sex-matched healthy control subjects (25 usable magnetic resonance spectroscopy data sets from the latter).. 31P magnetization transfer spectroscopy.. The primary outcome measure was the forward rate constant (k(f)) of the creatine kinase enzyme in the frontal lobe. We also collected independent measures of brain intracellular pH and steady-state metabolite ratios of high-energy phosphate-containing compounds (phosphocreatine and adenosine triphosphate [ATP]), inorganic phosphate, and the 2 membrane phospholipids phosphodiester and phosphomonoester.. A substantial (22%) and statistically significant (P = .003) reduction in creatine kinase kf was observed in SZ. In addition, intracellular pH was significantly reduced (7.00 in the SZ group vs 7.03 in the control group, P = .007) in this condition. The phosphocreatine to ATP ratio, inorganic phosphate to ATP ratio, and phosphomonoester to ATP ratio were not substantially altered in SZ, but a significant (P = .02) reduction was found in the phosphodiester to ATP ratio. The abnormalities were similar between SZ and schizoaffective disorder.. Using a novel 31P magnetization transfer magnetic resonance spectroscopy approach, we provide direct and compelling evidence for a specific bioenergetic abnormality in SZ. Reduced kf of the creatine kinase enzyme is consistent with an abnormality in storage and use of brain energy. The intracellular pH reduction suggests a relative increase in the contribution of glycolysis to ATP synthesis, providing convergent evidence for bioenergetic abnormalities in SZ. The similar phosphocreatine to ATP ratios in SZ and healthy controls suggest that the underlying bioenergetics abnormality is not associated with change in this metabolite ratio.

Topics: Adenosine Triphosphate; Adult; Brain; Brain Chemistry; Case-Control Studies; Creatine Kinase; Cross-Sectional Studies; Energy Metabolism; Female; Frontal Lobe; Humans; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Male; Phosphocreatine; Phosphorus Isotopes; Schizophrenia

Topics: Adenosine Triphosphate; Adult; Analysis of Variance; Asparagine; Diseases in Twins; Female; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Phosphocreatine; Phosphoric Monoester Hydrolases; Phosphorus Isotopes; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Twins, Monozygotic; Young Adult

Proton magnetic resonance spectroscopy ((1)H MRS) neurometabolite abnormalities have been detected widely in subjects with and at risk for schizophrenia. We hypothesized that such abnormalities would be present both in patients with schizophrenia and in their unaffected twin siblings. We acquired magnetic resonance spectra (TR/TE=3000/30 ms) at voxels in the mesial prefrontal gray matter, left prefrontal white matter and left hippocampus in 14 twin pairs discordant for schizophrenia (2 monozygotic, 12 dizygotic), 13 healthy twin pairs (4 monozygotic, 9 dizygotic) and 1 additional unaffected co-twin of a schizophrenia proband. In the mesial prefrontal gray matter voxel, N-acetylaspartate (NAA), creatine+phosphocreatine (Cr), glycerophosphocholine+phosphocholine (Cho) and myo-inositol (mI) did not differ significantly between patients with schizophrenia, their unaffected co-twins or healthy controls. However, glutamate (Glu) was significantly lower in patients with schizophrenia (31%, percent difference) and unaffected co-twins (21%) than in healthy controls (collapsed across twin pairs). In the left hippocampus voxel, levels of NAA (23%), Cr (22%) and Cho (36%) were higher in schizophrenia patients compared with controls. Hippocampal NAA (25%), Cr (22%) and Cho (37%) were also significantly higher in patients than in their unaffected co-twins. Region-to-region differences in metabolite levels were also notable within all three diagnosis groups. These findings suggest that (1)H MRS neurometabolite abnormalities are present not only in patients with schizophrenia, but also in their unaffected co-twins. Thus, reduced mesial prefrontal cortical Glu and elevated hippocampal NAA, Cr and Cho may represent trait markers of schizophrenia risk and, when exacerbated, state markers of schizophrenia itself.

Topics: Aspartic Acid; Creatine; Female; Glutamic Acid; Glycerylphosphorylcholine; Hippocampus; Humans; Inositol; Magnetic Resonance Spectroscopy; Male; Middle Aged; Nerve Fibers, Myelinated; Nerve Fibers, Unmyelinated; Phosphocreatine; Phosphorylcholine; Prefrontal Cortex; Protons; Schizophrenia; Twins, Dizygotic; Twins, Monozygotic

Authors analyzed biochemical (data obtained by proton MR spectroscopy) and hemodynamic ( data of fMRI) characteristics of the prefrontal cortex in 7 patients with juvenile shift-like schizophrenia examined during remission after the first episode and in 8 mentally healthy subjects matched for sex and age. The between-group differences in the tested parameters were not found, however, the neurobiological features of the prefrontal cortex were correlated with the psychopathological symptoms assessed with the PANSS.

Topics: Aspartic Acid; Biomarkers; Creatine; Female; Hemodynamics; Humans; Magnetic Resonance Imaging; Male; Phosphocreatine; Prefrontal Cortex; Schizophrenia; Young Adult

Magnetic resonance spectroscopy enables the in vivo analysis of certain aspects of brain biochemistry. Reduced N-acetylaspartate in key regions of schizophrenia has been reported repeatedly but not without controversy. Our objective is to investigate whether reduced N-acetylaspartate concentrations determined without correction for individual T2 relaxation time (referred to as 'apparent tNAA concentration') are due to a reduced absolute N-acetylaspartate concentration or to altered relaxation properties. For this purpose we measured absolute concentrations while evaluating individual T2 relaxation times. We evaluated the metabolite concentrations and metabolite/water relaxation times of a frontal white matter voxel from 23 patients who met DSM-IV criteria for schizophrenia and 29 healthy control subjects with similar age at a 3 T magnetic resonance scanner. A significantly reduced N-acetylaspartate concentration as well as shortened N-acetylaspartate's T2 relaxation time in the schizophrenic patient group was found. The apparent N-acetylaspartate concentration difference between healthy controls and patients with schizophrenia increased with the echo time due to a decreased N-acetylaspartate's T2 in the schizophrenic group. No group difference was found for any other metabolite concentration or metabolite/brain water relaxation time. These findings of reduced N-acetylaspartate as well as shortened N-acetylaspartate's T2 relaxation time give further evidence for microstructural white matter changes in schizophrenia. Furthermore, they elucidate why reports of a reduced N-acetylaspartate concentration in schizophrenia were not always corroborated.

Topics: Adult; Analysis of Variance; Aspartic Acid; Creatine; Dipeptides; Female; Frontal Lobe; Glutamic Acid; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Nerve Fibers, Myelinated; Phosphocreatine; Protons; Schizophrenia; Water

Schizophrenia is associated with significant brain abnormalities, including changes in brain metabolites as measured by proton magnetic resonance spectroscopy (MRS). What remains unclear is the extent to which these changes are a consequence of the emergence of psychotic disorders or the result of treatment with antipsychotic medication. We assessed 34 patients with first episode psychosis (15 antipsychotic naïve) and 19 age- and gender-matched controls using short-echo MRS in the medial temporal lobe bilaterally. Overall, there were no differences in any metabolite, regardless of treatment status. However, when the analysis was limited to patients with a diagnosis of schizophrenia, schizophreniform or schizoaffective disorder, significant elevations of creatine/phosphocreatine (Cr/PCr) and myo-inositol (mI) were found in the treated group. These data indicate a relative absence of temporal lobe metabolic abnormalities in first episode psychosis, but suggest that some treatment-related changes in mI might be apparent in patients with schizophrenia-spectrum diagnoses. Seemingly illness-related Cr/PCr elevations were also specific to the diagnosis of schizophrenia-spectrum disorder and seem worthy of future study.

Topics: Adult; Antipsychotic Agents; Aspartic Acid; Choline; Creatine; Female; Frontal Lobe; Functional Laterality; Humans; Image Processing, Computer-Assisted; Inositol; Magnetic Resonance Spectroscopy; Male; Phosphocreatine; Psychotic Disorders; Schizophrenia; Temporal Lobe

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.

Topics: Adult; Aged; Antipsychotic Agents; Aspartic Acid; Choline; Chronic Disease; Cognition Disorders; Creatine; Dominance, Cerebral; Energy Metabolism; Female; Frontal Lobe; Glutamic Acid; Glutamine; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Mental Recall; Middle Aged; Neurons; Phosphocreatine; Prefrontal Cortex; Psychiatric Status Rating Scales; Reference Values; Schizophrenia; Verbal Learning

Topics: Aspartic Acid; Choline; Creatine; Dominance, Cerebral; Glutamic Acid; Gyrus Cinguli; Hippocampus; Humans; Magnetic Resonance Spectroscopy; Phosphocreatine; Prefrontal Cortex; Reference Values; Schizophrenia; Thalamus

The study examined the high energy-phosphate metabolism of basal ganglia in antipsychotic-naive schizophrenia patients with and without developmental reflexes in comparison to healthy subjects. Nineteen antipsychotic-naive schizophrenics of whom 11 had developmental reflexes and 26 age-sex-matched healthy subjects without developmental reflexes underwent in-vivo 2-D 31P Magnetic Resonance Spectroscopy of basal ganglia on a 1.5-T scanner. Mean age-at-onset of psychosis was significantly lower in patients with developmental reflexes. Mean PCr/Total ATP ratio in bilateral basal ganglia was lower in patients than healthy subjects. The ratio was the least in patients with developmental reflexes (F=10.7; df=2, 42; p<0.001). Schizophrenia patients with developmental reflexes had the lowest PCr/Total ATP ratio in basal ganglia indicating more severe metabolic abnormality. These patients had younger age-at-onset of psychosis. Together, this suggests neurodevelopmental etiopathogenesis in schizophrenia.

Topics: Adenosine Triphosphate; Adult; Basal Ganglia; Female; Humans; Magnetic Resonance Spectroscopy; Male; Phosphocreatine; Psychiatric Status Rating Scales; Reflex; Schizophrenia; Schizophrenic Psychology

Recent magnetic resonance imaging studies have attempted to relate volumetric brain measurements in early schizophrenia to clinical and functional outcome some years later. These studies have generally been negative, perhaps because gray and white matter volumes inaccurately assess the underlying dysfunction that might be predictive of outcome.. To investigate the predictive value of frontal and temporal spectroscopy measures for outcome in patients with first-episode psychoses.. Left prefrontal cortex and left mediotemporal lobe voxels were assessed using proton magnetic resonance spectroscopy to provide the ratio of N-acetylaspartate (NAA) and choline-containing compounds to creatine and phosphocreatine (Cr) (NAA/Cr ratio). These data were used to predict outcome at 18 months after admission, as assessed by a systematic medical record audit.. Early psychosis clinic.. Forty-six patients with first-episode psychosis.. We used regression models that included age at imaging and duration of untreated psychosis to predict outcome scores on the Global Assessment of Functioning Scale, Clinical Global Impression scales, and Social and Occupational Functional Assessment Scale, as well as the number of admissions during the treatment period. We then further considered the contributions of premorbid function and baseline level of negative symptoms.. The only spectroscopic predictor of outcome was the NAA/Cr ratio in the prefrontal cortex. Low scores on this variable were related to poorer outcome on all measures. In addition, the frontal NAA/Cr ratio explained 17% to 30% of the variance in outcome.. Prefrontal neuronal dysfunction is an inconsistent feature of early psychosis; rather, it is an early marker of poor prognosis across the first years of illness. The extent to which this can be used to guide treatment and whether it predicts outcome some years after first presentation are questions for further research.

Topics: Adult; Aspartic Acid; Choline; Creatine; Female; Follow-Up Studies; Functional Laterality; Hippocampus; Humans; Magnetic Resonance Spectroscopy; Male; Outcome Assessment, Health Care; Patient Readmission; Phosphocreatine; Predictive Value of Tests; Prefrontal Cortex; Prognosis; Psychiatric Status Rating Scales; Psychotic Disorders; Schizophrenia; Temporal Lobe

To examine the volumetric and metabolic correlates of caudate nucleus in antipsychotic-naïve schizophrenia patients in comparison with healthy controls.. Twelve antipsychotic-naïve schizophrenia patients and 13 healthy controls underwent (31)P magnetic resonance spectroscopy of basal ganglia. Magnetic resonance imaging volume of caudate nuclei was measured using scion image software.. Patients had significantly smaller caudate volume than healthy controls. Phosphocreatine (PCr)/total phosphorous and PCr/total adenosine tri-phosphate ratios of both caudate nuclei were significantly lower in patients than controls. Significant negative correlation was found between the left caudate volume and left PCr/total phosphorus ratio in the patients. Age at onset of psychosis had i) significant negative correlation with right and left caudate volumes and ii) significant positive correlation with left PCr/total phosphorus ratio.. The metabolic and volumetric abnormalities of caudate nucleus in antipsychotic-naïve schizophrenia patients support neurodevelopmental etiopathogenesis.

Topics: Adenosine Triphosphate; Adult; Basal Ganglia; Caudate Nucleus; Corpus Striatum; Female; Functional Laterality; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Phosphocreatine; Phosphorus; Psychotropic Drugs; Schizophrenia

In adult schizophrenia, magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) have revealed volumetric and metabolic defects in multiple brain regions, among them the anterior cingulate, frontal cortex, striatum, thalamus, parietal cortex, and frontal and parietal white matter. This study used proton magnetic resonance spectroscopic imaging ((1)H MRSI) to identify potential metabolic abnormalities in these regions in childhood-onset schizophrenia. (1)H MRSI was acquired at 1.5 T and 272 ms echo time in 11 children and adolescents with schizophrenia (aged 7-18 years; seven boys, four girls; all but two medicated) and 20 age-matched healthy controls (10 boys, 10 girls). Absolute levels of N-acetyl compounds (NAA), creatine plus phosphocreatine (Cr), and choline compounds (Cho) were compared among groups in each region. In schizophrenic patients relative to controls, Cr was 14.3% higher in superior anterior cingulate (mean of left and right hemispheres). Cho was higher in superior anterior cingulate (30.3%), frontal cortex (13.3%), and caudate head (13.5%). In the thalamus, there was also a diagnosis-by-gender interaction, whereby NAA was lower in patients for male but not for female subjects. Elevated Cr suggests abnormal local cell-energy demand and elevated Cho is consistent with a prior proposal that patients with early age-of-onset schizophrenia exhibit phospholipid membrane disturbances. Low NAA may reflect diminished neuronal integrity.

Topics: Adolescent; Age Factors; Aspartic Acid; Brain; Brain Mapping; Caudate Nucleus; Child; Choline; Creatine; Dominance, Cerebral; Energy Metabolism; Frontal Lobe; Gyrus Cinguli; Humans; Image Interpretation, Computer-Assisted; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Phosphocreatine; Reference Values; Schizophrenia; Schizophrenic Psychology; Sex Factors; Thalamus

This study used 31-phosphorus magnetic resonance spectroscopy ((31)P MRS) to investigate basal ganglia abnormalities in neuroleptic-naive patients with schizophrenia.. Nineteen schizophrenia patients and 31 age- and sex-matched healthy comparison subjects underwent (31)P MRS.. The phosphocreatine/total phosphorus and phosphocreatine/total ATP ratios in both basal ganglia were significantly lower in patients.. Schizophrenia patients showed features of increased metabolism in the basal ganglia consistent with impaired activity of the frontostriatal pathways.

Topics: Adenosine Triphosphate; Adult; Antipsychotic Agents; Basal Ganglia; Energy Metabolism; Female; Humans; Magnetic Resonance Spectroscopy; Male; Neural Pathways; Phosphates; Phosphocreatine; Phosphorus; Phosphorus Isotopes; Schizophrenia

The hippocampus, thalamus and basal ganglia are among the brain regions of major interest in schizophrenia.. The purpose of this study was to corroborate previous findings of reduced N-acetylaspartate in the hippocampal and thalamic regions and to investigate possible metabolite changes in the putamen in schizophrenia.. MRSI study of the thalamus, basal ganglia, and hippocampus in 13 schizophrenic patients under stable medication and age-matched healthy controls.. A decrease of the N-acetylaspartate signal was found in the hippocampal region and the thalamus but not in the putamen of patients compared to controls. No significant group differences in the signals from creatine and phosphocreatine, and choline-containing compounds were found in the hippocampal region and the putamen but the signal from choline-containing compounds was decreased in the thalamus of patients.. Metabolic processes in the basal ganglia of schizophrenic patients seem to be opposite the hippocampal and thalamus findings.

Topics: Adult; Aspartic Acid; Basal Ganglia; Case-Control Studies; Choline; Female; Hippocampus; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Phosphocreatine; Putamen; Schizophrenia; Thalamus

Studies using proton magnetic resonance spectroscopy in schizophrenia have demonstrated abnormality of N-acetylaspartate but are confounded by the effects of phase of illness and medication. There is mounting evidence that antipsychotic medication influences N-acetylaspartate.. A group of first-episode patients who had received no, or minimal, antipsychotic medication was examined at baseline and after 3 months treatment. Normal comparison subjects were examined at the same interval. Ratios of N-acetylaspartate, creatine plus phosphocreatine, and choline-containing compounds in the left prefrontal cortex, hippocampus, and basal ganglia were measured.. The mean duration of symptoms for all patients was 31.6 (SD 26.1) weeks. A significant reduction of hippocampal N-acetylaspartate/creatine plus phosphocreatine was found in the antipsychotic-naive group relative to those previously treated and to controls at baseline (F = 7.3, p <.002). No group differences were found at follow-up.. Hippocampal N-acetylaspartate/creatine plus phosphocreatine appears to be selectively affected early in the course of illness. The finding of neurochemical differences between treatment naive and previously treated patients confirms the relevance of medication status in proton magnetic resonance spectroscopy studies. Further investigation of the influence of medication at this stage of illness is warranted.

Topics: Adolescent; Adult; Antipsychotic Agents; Aspartic Acid; Basal Ganglia; Case-Control Studies; Creatine; Female; Hippocampus; Humans; Male; Phosphocreatine; Prefrontal Cortex; Schizophrenia

Clinical, neuropsychological and functional neuroimaging studies in schizophrenia suggest impaired frontal lobe function, especially of the dorsolateral prefrontal region (DLPFR). This dysfunction has in particular been associated with negative or "deficit" symptoms. Despite these findings, morphological studies have failed to show consistent structural abnormalities in the frontal lobe. This may be because existing techniques are not sensitive enough to detect structural abnormalities or that dysfunction in the frontal lobe is caused by lesions elsewhere. We used volume-localised proton magnetic resonance spectroscopy (1H-MRS) to measure N-acetylaspartate (NAA), a neuronal marker, to evaluate the neuronal integrity of the dorsolateral prefrontal region in schizophrenic patients with persistent negative symptoms and in healthy comparison subjects.. Twenty-five patients who fulfilled DSM-IV criteria for schizophrenia and met the criteria for the Deficit syndrome were compared to 26 healthy controls matched for age and gender. Bilateral proton MR spectra were collected from a 2-cm(3) volume in the dorsolateral prefrontal region and the absolute concentrations of N-acetylaspartate, choline (Cho) and creatine+phosphocreatine (Cr+PCr) were measured.. There was a significant negative correlation between severity of symptoms and NAA concentration in the schizophrenic patients. This was more marked for positive symptoms and for general psychopathology than for negative symptoms. There was also a significant correlation between NAA concentration and social functioning within the schizophrenic group. There were no significant differences between the two groups for the three metabolites.. The negative association between severity of symptoms and NAA in schizophrenic patients and an association of NAA with social functioning suggest that NAA may be an indicator of disease severity. The lack of significant mean difference in NAA between the two groups suggests that there is no marked neuronal loss in the dorsolateral prefrontal region in schizophrenia.

Topics: Adult; Aspartic Acid; Brain Mapping; Choline; Creatine; Dominance, Cerebral; Energy Metabolism; Female; Frontal Lobe; Humans; Image Processing, Computer-Assisted; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Middle Aged; Phosphocreatine; Prefrontal Cortex; Psychiatric Status Rating Scales; Reference Values; Schizophrenia; Schizophrenic Psychology

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.

Topics: Adult; Antipsychotic Agents; Aspartic Acid; Basal Ganglia Diseases; Choline; Chronic Disease; Creatine; Dominance, Cerebral; Energy Metabolism; Female; Glutamic Acid; Glutamine; Humans; Inositol; Magnetic Resonance Spectroscopy; Male; Middle Aged; Neurologic Examination; Parkinson Disease, Secondary; Phosphocreatine; Putamen; Reference Values; Schizophrenia; Schizophrenic Psychology

Proton magnetic resonance spectra (MRS) were acquired from 1.5 x 1.5 x 1.5-cm voxels in the left and right mesial temporal lobes of 20 schizophrenic patients and 20 non-psychiatric comparison subjects. Choline (Cho) to creatine (and phosphocreatine) (Cr(PCr)) ratios were estimated as were the percent gray matter, white matter and CSF contributing to the voxel. The Cho/Cr(PCr) metabolite ratio was significantly lower in the left temporal lobe than in the right temporal lobe for both the schizophrenia subjects and control group. This difference was greater in the schizophrenia subjects. Left temporal lobe gray matter voxel content was significantly higher and white matter content was significantly lower than in the right temporal lobe for both the schizophrenia subjects and control group. This difference was the same for the schizophrenia subjects and control group. Left voxel gray matter and white matter content correlated with Cho/Cr(PCr) metabolite ratios for the schizophrenic subjects but not for the control subjects. No such correlations were noted on the right side. No significant difference was found between Cho/Cr(PCr) in the left temporal lobe or in the right temporal lobe of the schizophrenia subjects vs. the control group.

Topics: Adult; Choline; Chronic Disease; Creatine; Female; Functional Laterality; Humans; Magnetic Resonance Spectroscopy; Male; Phosphocreatine; Schizophrenia; Temporal Lobe

Most phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) studies have described measures of lower membrane anabolism or greater catabolism in the frontal lobes of patients with schizophrenia. The purpose of the present study was to evaluate whether these findings can also be detected in young subjects at genetic risk for schizophrenia.. Fourteen children and siblings of patients with schizophrenia (mean age=16.7 years) and 14 comparison subjects (mean age=16.9 years) were included in a (31)P-MRS study of the frontal lobe.. The high-risk subjects had significantly lower mean ratios of phosphomonoesters to phosphodiesters (0.25 versus 0.31) and higher mean phosphodiester values (37.59% versus 34.87%) than comparison subjects.. These findings suggest greater phospholipid breakdown even in young first-degree relatives of patients with schizophrenia. This suggestion is discussed with respect to the membrane phospholipid hypothesis of schizophrenia.

Topics: Adolescent; Brain; Brain Chemistry; Family; Female; Genetic Predisposition to Disease; Humans; Magnetic Resonance Spectroscopy; Male; Phosphates; Phosphocreatine; Phospholipids; Phosphorus Isotopes; Schizophrenia

Using proton magnetic resonance spectroscopic imaging, the authors measured thalamic N-acetylaspartate (NAA) concentrations in patients with schizophrenia.. The study included 15 schizophrenic patients on a stable medication regimen and 15 age-matched healthy comparison subjects. Concentrations of NAA, creatine plus phosphocreatine, and choline-containing compounds in bilateral thalamic regions were determined.. Previous findings of lower NAA concentration in the left and right mediodorsal region of the thalamus and significant correlations between left and right thalamic NAA measures in patients with schizophrenia were corroborated. Furthermore, the concentrations of choline-containing compounds were significantly lower in the schizophrenic patients. No group differences in creatine plus phosphocreatine were found.. There is strong evidence for neuronal dysfunction or loss in the mediodorsal region of the thalamus in patients with schizophrenia.

Topics: Adult; Aspartic Acid; Choline; Female; Functional Laterality; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Phosphocreatine; Schizophrenia; Thalamus

Single-voxel proton magnetic resonance spectroscopy was performed in 64 medicated schizophrenic patients and 51 healthy subjects. Spectra were obtained from a voxel in the left medial temporal lobe by using a 2.0-tesla whole-body magnetic resonance imaging system. Schizophrenic patients showed a lower N-acetylaspartate/ creatine-phosphocreatine ratio than did healthy subjects, and this reduction was greater in 13 patients with a family history of psychotic disorders.

Topics: Adult; Aspartic Acid; Choline; Creatine; Dominance, Cerebral; Energy Metabolism; Female; Genetic Predisposition to Disease; Humans; Magnetic Resonance Spectroscopy; Male; Phosphocreatine; Reference Values; Schizophrenia; Temporal Lobe

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.

Topics: Adult; Antipsychotic Agents; Aspartic Acid; Chronic Disease; Clozapine; Creatine; Female; Gyrus Cinguli; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Phosphocreatine; Reference Values; Risperidone; Schizophrenia; Treatment Outcome

Proton magnetic resonance spectroscopy (1H-MRS) was used to study medial prefrontal metabolic impairments in schizophrenic patients with the deficit syndrome.. The subjects were 22 schizophrenic patients categorized as deficit (N=5) or nondeficit (N=17) and 21 healthy subjects. (1)H-MRS was performed for the right and the left medial prefrontal cortex.. The patients with the deficit syndrome had significantly lower ratios of N-acetylaspartate to creatine plus phosphocreatine than did the healthy subjects or nondeficit patients.. As N-acetylaspartate levels could reflect neuronal density and/or viability, this finding suggests a neuronal loss in the medial prefrontal cortex of deficit patients.

Topics: Aspartic Acid; Cell Count; Creatine; Functional Laterality; Humans; Magnetic Resonance Spectroscopy; Neurons; Phosphocreatine; Prefrontal Cortex; Radionuclide Imaging; Schizophrenia; Schizophrenic Psychology

(31)Phosphorous magnetic resonance spectroscopy has been widely used to evaluate schizophrenic patients in comparison to control subjects, because it allows the investigation of both phospholipid and energy metabolism in vivo; however, the results achieved so far are inconsistent. Chemical shift imaging (CSI) has the advantage that instead of only one or a few preselected voxels the tissue of a whole brain slice can be examined. The aim of the present investigation was to determine whether the results of previous studies of our group, showing that phosphodiesters (PDE) are decreased in the frontal lobe of schizophrenic patients as compared to control subjects, might be confirmed in an independent unmedicated patient sample using the CSI technique.. A carefully selected new cohort including 11 neuroleptic-free schizophrenic patients and 11 age- and gender-matched healthy control subjects was recruited. CSI was applied and an innovative analysis method for CSI data based on a general linear model was used.. PDE, phosphocreatine, and adenosine triphosphate (ATP) were found to be significantly decreased in the frontal lobe of patients with schizophrenia.. Because PDE was decreased in schizophrenic patients, the membrane phospholipid hypothesis of schizophrenia could not be corroborated. Further results indicate decreased ATP production in the frontal lobe of patients with schizophrenia.

Topics: Adenosine Triphosphate; Adult; Brain; Case-Control Studies; Female; Frontal Lobe; Humans; Magnetic Resonance Spectroscopy; Male; Models, Neurological; Organophosphates; Phosphocreatine; Phospholipids; Phosphorus Isotopes; Schizophrenia

To investigate whether there are cerebellar vermis abnormalities in schizophrenia.. Prospective imaging study with proton magnetic resonance spectroscopy (1H-MRS).. Schizophrenia clinic at a large urban hospital.. Twelve right-handed male patients with schizophrenia, and 12 control subjects with no psychiatric history.. MRS data were acquired from a 2.0 x 2.0 x 2.0 cm volume of interest that included the entire cerebellar vermis.. Spectral peak arising from N-acetylaspartate (NAA), phosphocreatine/creatine (Cr) and choline (Cho).. There were no significant differences between the patients with schizophrenia and the controls in cerebellar vermis ratios of NAA to Cr (p = 0.71) or Cho to Cr (p = 0.50).. This study does not support earlier structural studies that found abnormalities of the cerebellar vermis in schizophrenia, although it does support reported neurochemical studies. It does not rule out cerebellar involvement in schizophrenia through mechanisms such as aberrant circuitry. Larger in vivo structural/neurochemical and functional imaging studies in other parts of the cerebellum are needed.

Topics: Adult; Aspartic Acid; Cerebellum; Choline; Creatine; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Phosphocreatine; Schizophrenia

The authors examined phospholipids and high-energy phosphorus metabolism in the temporal lobes of drug-naive schizophrenic patients.. In vivo 31P magnetic resonance spectroscopy was performed on 17 first-episode, drug-naive schizophrenic patients and 17 age- and gender-matched healthy subjects.. Patients showed higher levels of phosphodiesters and lower levels of phosphomonoesters than the comparison group. Phosphocreatine levels were increased in the left temporal lobes of patients.. The results suggest disturbed membrane phospholipid metabolism in both temporal lobes and decreased energy demands in the left temporal lobes of drug-naive schizophrenic patients.

Topics: Adult; Analysis of Variance; Brief Psychiatric Rating Scale; Esters; Ethanolamines; Female; Functional Laterality; Humans; Magnetic Resonance Spectroscopy; Male; Phosphocreatine; Phospholipids; Phosphorus; Phosphorus Isotopes; Phosphorylcholine; Schizophrenia; Temporal Lobe

Phosphorus-31 magnetic resonance spectroscopy ((31)P-MRS) has gained much interest in schizophrenia research in recent years since it allows the non-invasive measurement of high-energy phosphates and phospholipids in vivo. However, until now only differences in metabolite concentrations between certain brain areas of schizophrenic patients and healthy controls have been examined. We investigated the influence of gender on the concentrations of different phosphorus compounds. For this purpose, well-defined volumes in the frontal lobe of 32 healthy controls and 51 schizophrenic in-patients were examined with an image selected in vivo spectroscopy (ISIS) sequence on a whole-body scanner at 1.5 T. Healthy females exhibited increased values of inorganic phosphate (P(i)) and decreased values of phosphocreatine (PCr) in comparison to their male counterparts. In schizophrenic patients such gender differences were not present. Thus, the results can be interpreted in the sense that frontal energy demanding processes are enhanced in female compared to male healthy volunteers; schizophrenia seems to reduce these gender differences.

Topics: Adenosine Triphosphate; Adult; Female; Frontal Lobe; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Phosphocreatine; Schizophrenia; Sex Characteristics

In recent years, a number of 31phosphorus magnetic resonance spectroscopy (P-MRS) studies on the frontal lobe of schizophrenics have been performed, reporting alterations of phospholipids and high-energy phosphates. Deicken et al. (1994b) recently found positive correlations between left frontal phosphomonoester% (PME%) levels and the performance of a specific frontal lobe task, the Wisconsin Card Sorting Test (WCST), in schizophrenics. In the present paper, the correlations between phospholipids and high-energy phosphates in the frontal lobe of 26 schizophrenics and 23 controls measured with a volume-selective P-MRS method were investigated. Overall, we could not find any correlations between WCST results and phospholipid levels, but in controls phosphocreatine% (PCr%) and PCr/adenenosine triphosphate (ATP) ratios were negatively correlated with test performance. Since PCr behaves as a buffer of ATP, in the sense that when ATP is consumed by neuronal activity PCr is catalysed rapidly to ATP, increased PCr% values and, moreover, increased PCr/ATP ratios point to a decreased ATP consumption. Thus, the correlations found between PCr% and PCr/ATP and test performance in controls point to an association between reduced performance in a specific frontal lobe task and decreased energy demanding processes at rest. This association was not found in schizophrenics, possibly due to the influence of neuroleptic medication or the disease process per se.

Topics: Adenosine Triphosphate; Adult; Female; Frontal Lobe; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neuropsychological Tests; Phosphocreatine; Phosphorus Isotopes; Schizophrenia

Multislice proton magnetic resonance spectroscopic imaging (1H-MRSI) permits simultaneous acquisition and mapping of signal intensities of N-acetyl-containing compounds (mainly N-acetylaspartate, NAA), choline-containing compounds (CHO), and creatine plus phosphocreatine (CRE) from multiple whole-brain slices consisting of small single-volume elements. Previous 1H-MRSI studies of adult patients with schizophrenia showed small NAA relative signals in the hippocampal area and in the dorsolateral prefrontal cortex in comparison with healthy subjects. As part of a program to address the pathophysiological continuity between childhood-onset and adult-onset schizophrenia, the authors performed 1H-MRSI of patients with childhood-onset schizophrenia to specifically test whether the hippocampal area and dorsolateral prefrontal cortex show the same abnormalities as seen in adult-onset schizophrenia.. A 1.5-T nuclear magnetic resonance machine was used to test 14 patients (mean age, 16.4 years) and 14 comparison subjects. Ratios of areas under the metabolite peaks of the proton spectra were determined (i.e., NAA/CRE, NAA/CHO, CHO/CRE) for multiple cortical and subcortical regions.. The patients showed significantly lower NAA/CRE ratios bilaterally in the hippocampal area and the dorsolateral prefrontal cortex than the comparison subjects. There were no significant differences in CHO/CRE or in NAA ratios in any other area sampled.. The present study shows that patients with childhood-onset schizophrenia have smaller than normal regional NAA relative signals, suggesting neuronal damage or malfunction in the hippocampal area and dorsolateral prefrontal cortex. These differences were similar in magnitude to those found in patients with adult-onset schizophrenia. The present data extend other evidence of a biological continuum between childhood- and adult-onset schizophrenia.

Topics: Adolescent; Adult; Aspartic Acid; Cerebral Cortex; Choline; Creatine; Female; Hippocampus; Humans; Magnetic Resonance Spectroscopy; Male; Phosphocreatine; Prefrontal Cortex; Protons; Schizophrenia; Schizophrenia, Childhood

In the present investigation on 31P-magneto-resonance spectroscopic parameters in the frontal lobe, we found phosphocreatine levels and the ratio phosphocreatine/adenosine triphosphate to be increased (12.62 +/- 1.98% resp. 0.31 +/- 0.06) in 50 neuroleptic-treated schizophrenics, whereas no differences were detected in 10 neuroleptic-free patients (11.66 +/- 2.57% resp. 0.29 +/- 0.08) compared to 36 controls (11.37 +/- 1.45 resp. 0.29 +/- 0.04). This result points to a major role of neuroleptics in the metabolism of high-energy phosphates.

Topics: Adenosine Triphosphate; Adult; Antipsychotic Agents; Brief Psychiatric Rating Scale; Female; Frontal Lobe; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Phosphocreatine; Phosphorus; Schizophrenia

Proton spectra in the regions of the right and left basal ganglia were studied in 14 medicated patients with chronic schizophrenia using proton magnetic resonance spectroscopy (1H MRS). Ratios of N-acetyl-aspartate (NAA) to choline-containing compounds (Cho) were significantly reduced in the bilateral basal ganglia regions compared to normal subjects. The relative level of Cho was increased in the left basal ganglia region in comparison to normal subjects. This finding suggests the presence of disturbances in phospholipid metabolism in the basal ganglia. The level of NAA was decreased in the bilateral basal ganglia regions, which may indicate neuronal dysfunction. The 1H MRS study demonstrated dysfunctions in the basal ganglia regions in medicated patients with chronic schizophrenia.

Topics: Adult; Aspartic Acid; Basal Ganglia; Basal Ganglia Diseases; Brain Mapping; Choline; Chronic Disease; Creatine; Dominance, Cerebral; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Middle Aged; Neurocognitive Disorders; Phosphocreatine; Protons; Psychiatric Status Rating Scales; Schizophrenia

Several single-voxel proton magnetic resonance spectroscopy (1H-MRS) studies of patients with schizophrenia have found evidence of reductions of N-acetyl-aspartate (NAA) concentrations in the temporal lobes. Multislice proton magnetic resonance spectroscopy imaging (1H-MRSI) permits simultaneous acquisition and mapping of NAA, choline-containing compounds (CHO), and creatine/phosphocreatine (CRE) signal intensities from multiple whole brain slices consisting of 1.4-ml single-volume elements. We have used 1H-MRSI to assess the regional specificity of previously reported changes of metabolite signal intensities in schizophrenia. Hippocampal volume was also measured to test the relationship between 1H-MRSI findings and tissue volume in this region.. Ratios of areas under the metabolite peaks of the proton spectra were determined (i.e., NAA/CRE, NAA/CHO, CHO/CRE) for multiple cortical and subcortical regions in 10 inpatients with schizophrenia.. Patients showed significant reductions of NAA/CRE and NAA/CHO bilaterally in the hippocampal region and in the dorsolateral prefrontal cortex. There were no significant changes in CHO/CRE or in NAA ratios in any other area sampled. No significant correlation was found between metabolite ratios in the hippocampal region and its volume.. NAA-relative signal intensity reductions in schizophrenia appear to be remarkably localized, involving primarily the hippocampal region and the dorsolateral prefrontal cortex, two regions implicated prominently in the pathophysiology of this disorder.

Topics: Adult; Aspartic Acid; Brain; Choline; Creatinine; Female; Hippocampus; Humans; Magnetic Resonance Spectroscopy; Male; Phosphocreatine; Prefrontal Cortex; Protons; Schizophrenia

Effect of photic stimulation (PS) on energy metabolism in the human occipital cortex was examined by using phosphorus-31 magnetic resonance spectroscopy in 9 normal subjects. Phosphocreatine (PCr)/total phosphorus signal peak area ratio significantly decreased from 12.3% to 10.9% during the 12 minutes of PS (P < 0.05). PCr once returned to a normal level after PS (11.9%) but significantly decreased again 12-18 minutes after PS (10.8%; P < 0.05). Intracellular pH increased from 7.08 to 7.16 during PS, although this increase was not significant. These results suggest that functional alteration of energy metabolism in the brain is different from that in muscles.

Topics: Adult; Bipolar Disorder; Brain; Energy Metabolism; Female; Humans; Hydrogen-Ion Concentration; Magnetic Resonance Spectroscopy; Male; Middle Aged; Phosphocreatine; Photic Stimulation; Schizophrenia

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.

Topics: Adult; Choline; Creatine; Female; Functional Laterality; Hippocampus; Humans; Magnetic Resonance Imaging; Male; Phosphocreatine; Schizophrenia; Temporal Lobe

Magnetic resonance spectroscopy (one-dimensional chemical shift imaging) was used to measure membrane phospholipid metabolism and high-energy phosphate metabolism in the left and right frontal lobes of 27 schizophrenic patients. In the schizophrenic patients, the phosphomonoester peak area was decreased in bilateral frontal lobes compared with that in age-matched normal subjects. On the other hand, the peak area of beta-adenosine triphosphate was increased in the left frontal lobe in the schizophrenic group. The phosphocreatine peak area was increased in the left frontal lobe of schizophrenic patients with high scores on the Scale for the Assessment of Negative Symptoms (SANS).

Topics: Adenosine Triphosphate; Adolescent; Adult; Brain Mapping; Dominance, Cerebral; Energy Metabolism; Female; Frontal Lobe; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Organophosphates; Phosphates; Phosphocreatine; Phospholipids; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology

Proton magnetic resonance spectroscopy (MRS) was performed in 30 medicated schizophrenic patients and 30 normal subjects. Two groups, each containing 15 schizophrenic patients and 15 age-and sex-matched normal subjects, received MRS examinations for different volumes of interest, either the frontal lobe or the medial temporal lobe. Schizophrenic patients showed a decrease in the ratios of N-acetylaspartate (NAA)/choline-containing compounds (Cho) and NAA/creatine-phosphocreatine (Cr). The patients also showed an increase in the ratio of Cho/Cr in the left medial temporal lobe but not in the left frontal lobe. The age at onset of illness correlated positively with the ratios of NAA/Cho and NAA/Cr in the medial temporal lobe. No significant correlation was observed between the ratios of NAA/Cho, NAA/Cr, or Cho/Cr in the left medial temporal and frontal lobes and clinical symptomatology as assessed by the Scale for the Assessment of Negative Symptoms and the Positive and Negative Syndrome Scale.

Topics: Adult; Arousal; Aspartic Acid; Choline; Creatine; Dominance, Cerebral; Energy Metabolism; Female; Frontal Lobe; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Neurocognitive Disorders; Phosphocreatine; Psychiatric Status Rating Scales; Reference Values; Schizophrenia; Schizophrenic Psychology; Temporal Lobe

Water-suppressed 1H magnetic resonance spectra were recorded from two brain regions of psychiatric patients and normal volunteers. The two regions studied were (a) the basal ganglia structures surrounding the anterior horn of the lateral ventricle and (b) the occipital cortex. N-Acetylaspartate (NAA), phosphocreatine-creatine (PCr-Cr), choline and inositol resonances were seen in both regions. Ratios of metabolite peak integrals to PCr-Cr peak integral were calculated for each spectrum. To control for partial volume effects, comparisons between patients and controls were made only from identical regions i.e. basal ganglia vs basal ganglia, and likewise for occipital cortex. Metabolite ratios from the occipital region of patients were similar to those from the occipital region of normal subjects. Bipolar patients being treated with lithium had elevated NAA/PCr-Cr in the basal ganglia region when compared to normals. These patients also demonstrated elevated choline/PCr-Cr and inositol/PCr-Cr ratios in the basal ganglia region.

Topics: Adult; Aspartic Acid; Basal Ganglia; Bipolar Disorder; Choline; Creatine; Depressive Disorder; Energy Metabolism; Female; Humans; Image Processing, Computer-Assisted; Inositol; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Occipital Lobe; Phosphates; Phosphocreatine; Protons; Schizophrenia; Schizophrenic Psychology

Eleven schizophrenic patients and nine normal controls were studied using in vivo 31Phosphorous magnetic resonance spectroscopy (31P MRS) to test the hypothesis of metabolic asymmetry in the temporal lobes in schizophrenia. The controls did not demonstrate any asymmetry of phosphorous metabolite ratios, percentage of phosphorous metabolites, or pH. In the schizophrenics, however, phosphocreatine/beta-adenosine triphosphate (PCr/beta-ATP) and phosphocreatine/inorganic phosphate (PCr/Pi) effects appeared to primarily reflect higher ratios on the right side, while the percentage of beta-ATP appeared to primarily reflect higher relative concentrations in the left temporal lobe. Moreover, significant negative correlations were noted between total Brief Psychiatric Rating Scale scores and PCr/beta-ATP in both the right and left temporal lobes. These results support the hypothesis of an asymmetric distribution of 31P metabolites in the temporal lobe of schizophrenic patients, and also show an association between temporal lobe phosphorous metabolism and the severity of psychiatric symptomatology.

Topics: Adenosine Triphosphate; Dominance, Cerebral; Energy Metabolism; Humans; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Phosphates; Phosphocreatine; Pilot Projects; Psychiatric Status Rating Scales; Reference Values; Schizophrenia; Schizophrenic Psychology; Temporal Lobe

Postmortem brain tissues of schizophrenic patients were found to contain 5-10 times less water-soluble creatine kinase (BB CK) and 1.5-3 times less mitochondrial creatine kinase as compared to control. The major part of BB CK in schizophrenic brain tissues, contrary to control, was found to be insoluble in water (particulate form of BB CK) and could be extracted from brain tissue with strong denaturating agents. The particulate form of BB CK did not have any enzymatic activity but activity was found after the solubilization of this isoenzyme. The observed BB CK translocation into the particulate inactive form and the decrease of mitochondrial CK content to schizophrenic brains may reflect changes in the synthesis and the utilization of creatine phosphate.

Topics: Brain; Creatine Kinase; Frontal Lobe; Humans; Intracellular Fluid; Isoenzymes; Mitochondria; Myocardial Infarction; Phosphocreatine; Pneumonia; Protein Processing, Post-Translational; Schizophrenia

Topics: Adenosine Triphosphate; Antidepressive Agents; Biogenic Amines; Brain; Depression; Energy Metabolism; gamma-Aminobutyric Acid; Glucose; Humans; Hypoxia, Brain; Neurotransmitter Agents; Phosphocreatine; Receptors, Dopamine; Schizophrenia