Browse
Submit Data
Databases
API
Help

Dataset Information

9 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Impact of glutamate levels on neuronal response and cognitive abilities in schizophrenia.

ABSTRACT: Schizophrenia is characterized by impaired cognitive functioning, and brain regions involved in cognitive control processes show marked glutamatergic abnormalities. However, it is presently unclear whether aberrant neuronal response is directly related to the observed deficits at the metabolite level in schizophrenia. Here, 17 medicated schizophrenia patients and 17 matched healthy participants underwent functional magnetic resonance imaging (fMRI) when performing an auditory cognitive control task, as well as proton magnetic resonance spectroscopy ((1)H-MRS) in order to assess resting-state glutamate in the anterior cingulate cortex. The combined fMRI-(1)H-MRS analysis revealed that glutamate differentially predicted cortical blood-oxygen level-dependent (BOLD) response in patients and controls. While we found a positive correlation between glutamate and BOLD response bilaterally in the inferior parietal lobes in the patients, the corresponding correlation was negative in the healthy control participants. Further, glutamate levels predicted task performance in patients, such that lower glutamate levels were related to impaired cognitive control functioning. This was not seen for the healthy controls. These findings suggest that schizophrenia patients have a glutamate-related dysregulation of the brain network supporting cognitive control functioning. This could be targeted in future research on glutamatergic treatment of cognitive symptoms in schizophrenia.

SUBMITTER: Falkenberg LE

PROVIDER: S-EPMC3989526 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Cognitive abilities and 50- and 100-msec paired-click processes in schizophrenia.

Project description:Abnormal 50- and 100-msec event-related brain activity derived from paired-click procedures are well established in schizophrenia. There is little agreement on whether group differences in the ratio score, i.e., the ratio of EEG amplitude after the second stimulus (S2) to the amplitude after the first stimulus (S1), reflect an encoding or gating abnormality. In addition, the functional implications remain unclear. In the present study, EEG and magnetoencephalography (MEG) were used to examine paired-click measures and cognitive correlates of paired-click activity.EEG and whole-cortex MEG data were acquired during the standard paired-click paradigm in 73 comparison subjects and 79 schizophrenia patients. Paired-click ratio scores were obtained at 50 msec (P50 evoked potential at Cz, M50 at left and right superior temporal gyrus [STG]) and 100 msec (N100 at Cz, M100 at left and right STG). A cognitive battery assessing attention, working memory, and long-delay memory was administered. IQ was also estimated.Groups differed on ratio score and amplitude of S1 response. Ratio scores at 50 msec and 100 msec and S1 amplitude predicted variance in attention (primarily S1 amplitude), working memory, and long-delay memory. The attention findings remained after removal of variance associated with IQ.Associations between paired-click measures and cognitive performance in patients support 50-msec and 100-msec ratio and amplitude scores as clinically significant biomarkers of schizophrenia. In general, cognitive performance was better predicted by the ability to encode auditory information than the ability to filter redundant information.

| S-EPMC3272497 | biostudies-literature

Widespread Volumetric Reductions in Schizophrenia and Schizoaffective Patients Displaying Compromised Cognitive Abilities.

Project description:ObjectiveProgress toward understanding brain mechanisms in psychosis is hampered by failures to account for within-group heterogeneity that exists across neuropsychological domains. We recently identified distinct cognitive subgroups that might assist in identifying more biologically meaningful subtypes of psychosis. In the present study, we examined whether underlying structural brain abnormalities differentiate these cognitively derived subgroups.Method1.5T T1 weighted structural scans were acquired for 168 healthy controls and 220 patients with schizophrenia/schizoaffective disorder. Based on previous work, 47 patients were categorized as being cognitively compromised (impaired premorbid and current IQ), 100 as cognitively deteriorated (normal premorbid IQ, impaired current IQ), and 73 as putatively cognitively preserved (premorbid and current IQ within 1 SD of controls). Global, subcortical and cortical volume, thickness, and surface area measures were compared among groups.ResultsWhole cortex, subcortical, and regional volume and thickness reductions were evident in all subgroups compared to controls, with the largest effect sizes in the compromised group. This subgroup also showed abnormalities in regions not seen in the other patient groups, including smaller left superior and middle frontal areas, left anterior and inferior temporal areas and right lateral medial and inferior frontal, occipital lobe and superior temporal areas.ConclusionsThis pattern of more prominent brain structural abnormalities in the group with the most marked cognitive impairments-both currently and putatively prior to illness onset, is consistent with the concept of schizophrenia as a progressive neurodevelopmental disorder. In this group, neurodevelopmental and neurodegenerative factors may be important for cognitive function.

| S-EPMC5890481 | biostudies-literature

Uric formaldehyde levels are negatively correlated with cognitive abilities in healthy older adults.

Project description:Recent studies have shown that the abnormal accumulation of endogenous formaldehyde could be a critical factor in age-related cognitive decline. The aim of this study was to estimate the correlation between uric formaldehyde and general cognitive abilities in a community-based elderly population, and to measure the extent and direction in which the correlation varied with demographic characteristics. Using a double-blind design, formaldehyde in human urine was analyzed by high-performance liquid chromatography (n = 604), and general cognitive abilities were measured using the Montreal Cognitive Assessment (MoCA). Demographic characteristics, in terms of age, gender, residential region, and education were taken into consideration. We found that uric formaldehyde levels were inversely correlated with the MoCA score, and the concentration varied with demographic features: higher odds of a high formaldehyde level occurred among the less educated and those living in old urban or rural areas. In cytological experiments, the level of cellular formaldehyde released into the medium increased as SH-SY5Y and BV2 cells were incubated for three days. Formaldehyde in excess impaired the processes of N2a cells and neurites of primary cultured rat hippocampal cells. However, removal of formaldehyde markedly rescued and regenerated the processes of N2a cells. These results demonstrated a negative correlation between the endogenous formaldehyde and general cognitive abilities. High formaldehyde levels could be a risk factor for cognitive impairment in older adults, and could be developed as a non-invasive marker for detection and monitoring of age-related cognitive impairment.

| S-EPMC5562661 | biostudies-other

Glutamate Networks Implicate Cognitive Impairments in Schizophrenia: Genome-Wide Association Studies of 52 Cognitive Phenotypes.

Project description:Cognitive impairments are a core feature in patients with schizophrenia. These deficits could serve as effective tools for understanding the genetic architecture of schizophrenia. This study investigated whether genetic variants associated with cognitive impairments aggregate in functional gene networks related to the pathogenesis of schizophrenia. Here, genome-wide association studies (GWAS) of a range of cognitive phenotypes relevant to schizophrenia were performed in 411 healthy subjects. We attempted to replicate the GWAS data using 257 patients with schizophrenia and performed a meta-analysis of the GWAS findings and the replicated results. Because gene networks, rather than a single gene or genetic variant, may be strongly associated with the susceptibility to schizophrenia and cognitive impairments, gene-network analysis for genes in close proximity to the replicated variants was performed. We observed nominal associations between 3054 variants and cognitive phenotypes at a threshold of P < 1.0 × 10(-) (4). Of the 3054 variants, the associations of 191 variants were replicated in the replication samples (P < .05). However, no variants achieved genome-wide significance in a meta-analysis (P > 5.0 × 10(-) (8)). Additionally, 115 of 191 replicated single nucleotide polymorphisms (SNPs) have genes located within 10 kb of the SNPs (60.2%). These variants were moderately associated with cognitive phenotypes that ranged from P = 2.50 × 10(-) (5) to P = 9.40 × 10(-) (8). The genes located within 10 kb from the replicated SNPs were significantly grouped in terms of glutamate receptor activity (false discovery rate (FDR) q = 4.49 × 10(-) (17)) and the immune system related to major histocompatibility complex class I (FDR q = 8.76 × 10(-) (11)) networks. Our findings demonstrate that genetic variants related to cognitive trait impairment in schizophrenia are involved in the N-methyl-d-aspartate glutamate network.

| S-EPMC4466179 | biostudies-literature

Impact of Early-Life Weight Status on Cognitive Abilities in Children.

Project description:OBJECTIVE:Whether obesity is associated with childhood cognition is unknown. Given the sensitivity of the developing brain to environmental factors, this study examined whether early-life weight status was associated with children's cognition. METHODS:Using data from mother-child pairs enrolled in the Health Outcomes and Measures of the Environment (HOME) Study (2003-2006), children's early-life weight status was assessed using weight-for-length/height standard deviation (SD) scores. A battery of neuropsychological tests was administered to assess cognition, executive function, and visual-spatial abilities at ages 5 and 8 years. Using linear mixed models, associations between early-life weight status and cognition were estimated. RESULTS:Among 233 children, 167 were lean (≤1 SD) and 48 were nonlean (>1 SD). After covariate adjustment, the results suggest that full-scale intelligence quotient scores decreased with a 1-unit increase in weight-for-height SD score (β = -1.4, 95% CI: -3.0 to 0.1). For individual component scores, with a 1-unit increase in weight-for-height SD score, perceptual reasoning (β = -1.7, 95% CI: -3.3 to 0.0) and working memory (β: -2.4, CI: -4.4 to -0.4) scores decreased. Weight status was generally not associated with other cognition measures. CONCLUSIONS:Within this cohort of typically developing children, early-life weight status was inversely associated with children's perceptual reasoning and working memory scores and possibly with full-scale intelligent quotient scores.

| S-EPMC5975980 | biostudies-literature

Glutathione Levels and Glutathione-Glutamate Correlation in Patients With Treatment-Resistant Schizophrenia.

Project description:Treatment-resistant schizophrenia (TRS) has been suggested to involve glutamatergic dysfunction. Glutathione (GSH), a dominant antioxidant, is known to be involved in glutamatergic neurotransmission. To date, no study has examined GSH levels in patients with TRS. The aim of this study was to examine GSH levels in the dorsal anterior cingulate cortex (dACC) of patients with TRS. Patients with schizophrenia were categorized into 3 groups with respect to their antipsychotic response: (1) clozapine (CLZ) nonresponders, (2) CLZ responders, and (3) first-line responders (FLR). GSH and glutamine + glutamate (Glx) levels were measured using 3T proton magnetic resonance spectroscopy. Firstly, dACC GSH levels were compared among the patient groups and healthy controls (HCs). Further, relationships between GSH and Glx levels were compared between the groups and GSH levels were explored stratifying the patient groups based on the glutamate-cysteine ligase catalytic (GCLC) subunit polymorphism. There was no difference in GSH levels between the groups. FLR showed a more negative relationship between GSH and Glx levels in the dACC compared to HCs. There were no effects of GCLC genotype on the GSH levels. However, CLZ responders had a higher ratio of high-risk GCLC genotype compared to CLZ nonresponders. This study demonstrated different relationships between GSH and Glx in the dACC between groups. In addition, the results suggest a potential link between CLZ response and GCLC genotype. However, it still remains unclear how these differences are related to the underlying pathophysiology of schizophrenia subtypes or the mechanisms of action of CLZ.

| S-EPMC8086698 | biostudies-literature

Blood Levels of Glutamate and Glutamine in Recent Onset and Chronic Schizophrenia.

Project description:Converging evidence indicates that dysfunctions in glutamatergic neurotransmission and in the glutamate-glutamine cycle play a role in the pathophysiology of schizophrenia. Here, we investigated glutamate and glutamine levels in the blood of patients with recent onset schizophrenia or chronic schizophrenia compared to healthy controls. Compared with healthy controls, patients with recent onset schizophrenia showed increased glutamine/glutamate ratio, while patients with chronic schizophrenia showed decreased glutamine/glutamate ratio. Results indicate that circulating glutamate and glutamine levels exhibit a dual behavior in schizophrenia, with an increase of glutamine/glutamate ratio at the onset of schizophrenia followed by a decrease with progression of the disorder. Further studies are warranted to elucidate the mechanisms and consequences of changes in circulating glutamate and glutamine in schizophrenia.

| S-EPMC6305751 | biostudies-literature

Anterior Cingulate Cortex Glutamate Levels Are Related to Response to Initial Antipsychotic Treatment in Drug-Naive First-Episode Schizophrenia Patients.

Project description:The glutamatergic system has previously been shown to be involved in the pathophysiology of schizophrenia and the mechanisms of action of antipsychotic treatment. The present study aimed to investigate the relationship between the levels of glutamate (Glu) or Glu/total creatine (Glu/Cr+PCr) in the anterior cingulate cortex (ACC) and psychiatric symptoms as well as the response to antipsychotic treatment. We performed proton magnetic resonance spectroscopy (1H-MRS) to measure Glu and Glu/Cr+PCr in the ACC of 35 drug-naïve first-episode schizophrenia (FES) patients and 40 well-matched healthy controls (HCs). After scanning, we treated the patients with risperidone for eight weeks. Remission status was based on the Positive and Negative Syndrome Scale (PANSS) scores at week 8. At baseline, there were no significant differences in the levels of Glu or Glu/Cr+PCr in the ACC between drug-naïve FES patients and HCs. Lower baseline levels of Glu/Cr+PCr but not Glu in the ACC were associated with more severe negative symptoms of schizophrenia. Compared to the remission group (RM), the non-remission group (NRM) had lower baseline ACC Glu levels (P < 0.05). Our results suggest that ACC Glu levels may be related to the severity of symptoms in the early stages of schizophrenia and therefore may be a marker with which to evaluate the treatment effect of antipsychotics in schizophrenia patients.

| S-EPMC7644538 | biostudies-literature

Linking GABA and glutamate levels to cognitive skill acquisition during development.

Project description:Developmental adjustments in the balance of excitation and inhibition are thought to constrain the plasticity of sensory areas of the cortex. It is unknown however, how changes in excitatory or inhibitory neurochemical expression (glutamate, γ-aminobutyric acid (GABA)) contribute to skill acquisition during development. Here we used single-voxel proton magnetic resonance spectroscopy (1H-MRS) to reveal how differences in cortical glutamate vs. GABA ratios relate to face proficiency and working memory abilities in children and adults. We show that higher glutamate levels in the inferior frontal gyrus correlated positively with face processing proficiency in the children, but not the adults, an effect which was independent of age-dependent differences in underlying cortical gray matter. Moreover, we found that glutamate/GABA levels and gray matter volume are dissociated at the different maturational stages. These findings suggest that increased excitation during development is linked to neuroplasticity and the acquisition of new cognitive skills. They also offer a new, neurochemical approach to investigating the relationship between cognitive performance and brain development across the lifespan.

| S-EPMC4832309 | biostudies-literature

Neuronal Elav-like (Hu) proteins regulate RNA splicing and abundance to control glutamate levels and neuronal excitability.

Project description:The paraneoplastic neurologic disorders target several families of neuron-specific RNA binding proteins (RNABPs), revealing that there are unique aspects of gene expression regulation in the mammalian brain. Here, we used HITS-CLIP to determine robust binding sites targeted by the neuronal Elav-like (nElavl) RNABPs. Surprisingly, nElav protein binds preferentially to GU-rich sequences in vivo and in vitro, with secondary binding to AU-rich sequences. nElavl null mice were used to validate the consequence of these binding events in the brain, demonstrating that they bind intronic sequences in a position dependent manner to regulate alternative splicing and to 3'UTR sequences to regulate mRNA levels. These controls converge on the glutamate synthesis pathway in neurons; nElavl proteins are required to maintain neurotransmitter glutamate levels, and the lack of nElavl leads to spontaneous epileptic seizure activity. The genome-wide analysis of nElavl targets reveals that one function of neuron-specific RNABPs is to control excitation-inhibition balance in the brain.

| S-EPMC3517991 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data