Dataset Information

Glutamate as a marker of cognitive function in schizophrenia: a proton spectroscopic imaging study at 4 Tesla.

ABSTRACT: Cognitive deficits in schizophrenia may be related to glutamatergic dysfunction, but in vivo measurement of glutamate metabolism has been challenging. We examined the relationship between glutamate metabolism and cognitive function in schizophrenia.Thirty subjects with DSM-IV schizophrenia and 28 healthy volunteers were studied using 4 Tesla proton echo planar spectroscopic imaging. Glutamate plus glutamine (Glx), N-acetylaspartate compounds, and Inositol concentrations in gray and white matter and broad neuropsychological function were assessed in all subjects.Glutamate plus glutamine was positively correlated with overall cognitive performance in the schizophrenia group (p = .0006), accounting for about 36% of the variance. No correlation was found in control subjects. Group-averaged Glx levels were similar in schizophrenia and control subjects. N-acetylaspartate compounds were reduced in cortical gray matter in the younger schizophrenia subjects (age < 30; p = .04) compared with age-matched control subjects. Inositol was increased in cortical gray (p = .002) and white matter (p = .02) in the older schizophrenia subjects (age > 30) compared with age-matched control subjects.Although not reduced in schizophrenia as a group, lower Glx levels correlates with impaired cognition in the illness. This suggests heterogeneity in mechanisms that regulate glutamate function in schizophrenia. Patients with reduced glutamatergic reserves may be rendered into a more severe hypoglutamatergic state with cognitive consequences. Reduced cortical gray matter N-acetylaspartate compound concentration early in the illness with normalization in older subjects is consistent with a process of early dendritic retraction with subsequent increased neuronal packing. Later in the illness, Inositol elevation suggests glial involvement.

SUBMITTER: Bustillo JR

PROVIDER: S-EPMC3005949 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Glutamate as a marker of cognitive function in schizophrenia: a proton spectroscopic imaging study at 4 Tesla.

Bustillo Juan R JR Chen Hongji H Gasparovic Charles C Mullins Paul P Caprihan Arvind A Qualls Clifford C Apfeldorf William W Lauriello John J Posse Stefan S

Biological psychiatry 20101020 1

<h4>Background</h4>Cognitive deficits in schizophrenia may be related to glutamatergic dysfunction, but in vivo measurement of glutamate metabolism has been challenging. We examined the relationship between glutamate metabolism and cognitive function in schizophrenia.<h4>Methods</h4>Thirty subjects with DSM-IV schizophrenia and 28 healthy volunteers were studied using 4 Tesla proton echo planar spectroscopic imaging. Glutamate plus glutamine (Glx), N-acetylaspartate compounds, and Inositol conce ...[more]

PMID: 20970118

Similar Datasets

Project description:Background and purposeThe secondary progressive phase of multiple sclerosis is characterised by disability progression due to processes that lead to neurodegeneration. Surrogate markers such as those derived from MRI are beneficial in understanding the pathophysiology that drives disease progression and its relationship to clinical disability. We undertook a 1H-MRS imaging study in a large secondary progressive MS (SPMS) cohort, to examine whether metabolic markers of brain injury are associated with measures of disability, both physical and cognitive.Materials and methodsA cross-sectional analysis of individuals with secondary-progressive MS was performed in 119 participants. They underwent 1H-MR spectroscopy to obtain estimated concentrations and ratios to total Cr for total NAA, mIns, Glx, and total Cho in normal-appearing WM and GM. Clinical outcome measures chosen were the following: Paced Auditory Serial Addition Test, Symbol Digit Modalities Test, Nine-Hole Peg Test, Timed 25-foot Walk Test, and the Expanded Disability Status Scale. The relationship between these neurometabolites and clinical disability measures was initially examined using Spearman rank correlations. Significant associations were then further analyzed in multiple regression models adjusting for age, sex, disease duration, T2 lesion load, normalized brain volume, and occurrence of relapses in 2 years preceding study entry.ResultsSignificant associations, which were then confirmed by multiple linear regression, were found in normal-appearing WM for total NAA (tNAA)/total Cr (tCr) and the Nine-Hole Peg Test (ρ = 0.23; 95% CI, 0.06-0.40); tNAA and tNAA/tCr and the Paced Auditory Serial Addition Test (ρ = 0.21; 95% CI, 0.03-0.38) (ρ = 0.19; 95% CI, 0.01-0.36); mIns/tCr and the Paced Auditory Serial Addition Test, (ρ = -0.23; 95% CI, -0.39 to -0.05); and in GM for tCho and the Paced Auditory Serial Addition Test (ρ = -0.24; 95% CI, -0.40 to -0.06). No other GM or normal-appearing WM relationships were found with any metabolite, with associations found during initial correlation testing losing significance after multiple linear regression analysis.ConclusionsThis study suggests that metabolic markers of neuroaxonal integrity and astrogliosis in normal-appearing WM and membrane turnover in GM may act as markers of disability in secondary-progressive MS.

Project description:Background and purposeEarly diagnosis of amnestic mild cognitive impairment (aMCI) and timely management to delay the onset of Alzheimer's disease (AD) would benefit patients. Pathological metabolic changes of excitatory/inhibitory neurotransmitters and abnormal protein deposition in the hippocampus of aMCI may provide a new clue to imaging diagnosis. However, the diagnostic performance using these hippocampal metabolite measurements is still unclear. We aimed to quantify right hippocampal glutamate-glutamine (Glx) and gamma-aminobutyric acid (GABA) levels as well as protein-based amide proton transfer-weighted (APTw) signals of patients with aMCI and investigate the diagnostic performance of these metabolites.MethodsIn this cross-sectional study, 20 patients with aMCI and 20 age- and gender-matched healthy controls (HCs) underwent MEGA Point Resolved Spectroscopy (MEGA-PRESS) and APTw MR imaging at 3 T. GABA+, Glx, and APTw signals were measured in the right hippocampus. The GABA+ levels, Glx levels, Glx/GABA+ ratios, and APTw values were compared between the HCs and aMCI groups using the Mann-Whitney U test. Binary logistic regression and receiver operating characteristic (ROC) curve analyses were used to evaluate MEGA-PRESS and APTw parameters' diagnostic performance.ResultsCompared with HCs, patients with aMCI had significantly lower Glx levels in the right hippocampus (7.02 ± 1.41 i.u. vs. 5.81 ± 1.33 i.u., P = 0.018). No significant changes in the GABA+ levels were observed in patients with aMCI (HCs vs. aMCI: 2.54 ± 0.28 i.u. vs. 2.47 ± 0.36 i.u., P = 0.620). In addition, Glx/GABA+ ratios between the two groups (HCs vs. aMCI: 2.79 ± 0.60 vs. 2.37 ± 0.55, P = 0.035) were significantly different. Compared with HCs, patients with aMCI showed higher APTw values in the right hippocampus (0.99 ± 0.26% vs. 1.26% ± 0.28, P = 0.006). The ROC curve analysis showed that Glx, GABA+, Glx/GABA+, and APTw values had an area under the curve (AUC) of 0.72, 0.55, 0.70, and 0.75, respectively, for diagnosing aMCI. In the ROC curve analysis, the AUC of the combination of the parameters increased to 0.88, which is much higher than that observed in the univariate analysis (P < 0.05).ConclusionThe combination of right hippocampal Glx levels and APTw values improved the diagnostic performance for aMCI, indicating it as a promising combined imaging diagnostic marker. Our study provided a potential imaging diagnostic strategy of aMCI, which may promote early detection of aMCI and facilitate timely intervention to delay the pathological progress toward AD.

Dataset Information

Glutamate as a marker of cognitive function in schizophrenia: a proton spectroscopic imaging study at 4 Tesla.

Publications

Glutamate as a marker of cognitive function in schizophrenia: a proton spectroscopic imaging study at 4 Tesla.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets