Non-linear variations in glutamate dynamics during a cognitive task engagement in schizophrenia.

To investigate the role of glutamate in psychosis, we employ functional magnetic resonance spectroscopy at an ultra-high magnetic field (7T) and employ fuzzy-approximate entropy (F-ApEn) and Hurst Exponent (HE) to capture time-varying nature of glutamate signaling during a cognitive task. We recruited thirty first-episode psychosis patients (FEP) with age- and gender-matched healthy controls (HC) and administered the Color-Word Stroop paradigm, providing 128 raw MRS time-points per subject over a period of 16 min. We then performed metabolite quantification of glutamate in the dorsal anterior cingulate cortex, a region reliably activated during the Stroop task.

Variability and magnitude of brain glutamate levels in schizophrenia: a meta and mega-analysis.

Glutamatergic dysfunction is implicated in schizophrenia pathoaetiology, but this may vary in extent between patients. It is unclear whether inter-individual variability in glutamate is greater in schizophrenia than the general population. We conducted meta-analyses to assess (1) variability of glutamate measures in patients relative to controls (log coefficient of variation ratio: CVR); (2) standardised mean differences (SMD) using Hedges g; (3) modal distribution of individual-level glutamate data (Hartigan's unimodality dip test).

Microstructural imaging and transcriptomics of the basal forebrain in first-episode psychosis.

Cholinergic dysfunction has been implicated in the pathophysiology of psychosis and psychiatric disorders such as schizophrenia, depression, and bipolar disorder. The basal forebrain (BF) cholinergic nuclei, defined as cholinergic cell groups Ch1-3 and Ch4 (Nucleus Basalis of Meynert; NBM), provide extensive cholinergic projections to the rest of the brain. Here, we examined microstructural neuroimaging measures of the cholinergic nuclei in patients with untreated psychosis (~31 weeks of psychosis, <2 defined daily dose of antipsychotics) and used magnetic resonance spectroscopy (MRS) and transcriptomic data to support our findings.

Widespread cortical thinning, excessive glutamate and impaired linguistic functioning in schizophrenia: A cluster analytic approach.

Introduction: Symptoms of schizophrenia are closely related to aberrant language comprehension and production. Macroscopic brain changes seen in some patients with schizophrenia are suspected to relate to impaired language production, but this is yet to be reliably characterized. Since heterogeneity in language dysfunctions, as well as brain structure, is suspected in schizophrenia, we aimed to first seek patient subgroups with different neurobiological signatures and then quantify linguistic indices that capture the symptoms of "negative formal thought disorder" (i.

CD26 is a senescence marker associated with reduced immunopotency of human adipose tissue-derived multipotent mesenchymal stromal cells.

Introduction: Human mesenchymal stromal cells (MSCs) have immunomodulatory, anti-inflammatory, and tolerogenic effects. Long-term in vitro expansion of MSCs to generate clinical grade products results in the accumulation of senescent-functionally impaired MSCs. Markers to assess the 'senescent load' of MSC products are needed.

Cortical impoverishment in a stable subgroup of schizophrenia: Validation across various stages of psychosis.

Background: Cortical thinning is a well-known feature in schizophrenia. The considerable variation in the spatial distribution of thickness changes has been used to parse heterogeneity. A 'cortical impoverishment' subgroup with a generalized reduction in thickness has been reported.

Central Oxidative Stress and Early Vocational Outcomes in First Episode Psychosis: A 7-Tesla Magnetic Resonance Spectroscopy Study of Glutathione.

Background And Hypothesis: Following the first episode of psychosis, some patients develop poor social and occupational outcomes, while others display a pattern of preserved functioning. Evidence from preclinical, genetic, and biochemical studies suggest a role for high oxidative stress in poor functional outcomes among patients. The measurement of intracortical glutathione (GSH) using magnetic resonance spectroscopy (MRS) enables investigating the relationship between central antioxidant tone and functional outcomes at the time of first-episode psychosis (FEP).

Is There a Glutathione Centered Redox Dysregulation Subtype of Schizophrenia?

Schizophrenia continues to be an illness with poor outcome. Most mechanistic changes occur many years before the first episode of schizophrenia; these are not reversible after the illness onset. A developmental mechanism that is still modifiable in adult life may center on intracortical glutathione (GSH).

The trajectory of putative astroglial dysfunction in first episode schizophrenia: a longitudinal 7-Tesla MRS study.

Myo-inositol is mainly found in astroglia and its levels has been shown to be reduced in the anterior cingulate cortex (ACC) of patients with schizophrenia. We investigate the status of astroglial integrity indexed by ACC myo-inositol at the onset and over the first 6 months of treatment of first episode schizophrenia. We employed 7 T magnetic resonance spectroscopy (1H-MRS) and quantified myo-inositol spectra at the dorsal ACC in 31 participants; 21 patients with schizophrenia with median lifetime antipsychotic exposure of less than 3 days, followed up after 6 months of treatment, and 10 healthy subjects scanned twice over the same period.

Progressive Changes in Glutamate Concentration in Early Stages of Schizophrenia: A Longitudinal 7-Tesla MRS Study.

Progressive reduction in glutamatergic transmission has been proposed as an important component of the illness trajectory of schizophrenia. Despite its popularity, to date, this notion has not been convincingly tested in patients in early stages of schizophrenia. In a longitudinal 7T magnetic resonance spectroscopy (1H-MRS), we quantified glutamate at the dorsal anterior cingulate cortex in 21 participants with a median lifetime antipsychotic exposure of less than 3 days and followed them up after 6 months of treatment.

Glutathione as a Molecular Marker of Functional Impairment in Patients with At-Risk Mental State: 7-Tesla H-MRS Study.

A substantial number of individuals with clinical high-risk (CHR) mental state do not transition to psychosis. However, regardless of future diagnostic trajectories, many of these individuals develop poor social and occupational functional outcomes. The levels of glutathione, a crucial cortical antioxidant, may track variations in functional outcomes in early psychosis and prodromal states.

Acute conceptual disorganization in untreated first-episode psychosis: a combined magnetic resonance spectroscopy and diffusion imaging study of the cingulum.

Background: Disorganized thinking is a core feature of acute psychotic episodes that is linked to social and vocational functioning. Several lines of evidence implicate disrupted cognitive control, excitatory overdrive and oxidative stress relating to the anterior cingulate cortex as mechanisms of conceptual disorganization (CD). We examined 3 candidate mechanistic markers related to CD in firstepisode psychosis: glutamate excess, cortical antioxidant (glutathione) status and the integrity of the cingulum bundle that connects regions implicated in cognitive control.

Association of Age, Antipsychotic Medication, and Symptom Severity in Schizophrenia With Proton Magnetic Resonance Spectroscopy Brain Glutamate Level: A Mega-analysis of Individual Participant-Level Data.

Importance: Proton magnetic resonance spectroscopy (1H-MRS) studies indicate that altered brain glutamatergic function may be associated with the pathophysiology of schizophrenia and the response to antipsychotic treatment. However, the association of altered glutamatergic function with clinical and demographic factors is unclear.

Objective: To assess the associations of age, symptom severity, level of functioning, and antipsychotic treatment with brain glutamatergic metabolites.

Hippocampal neuroanatomy in first episode psychosis: A putative role for glutamate and serotonin receptors.

Disrupted serotonergic and glutamatergic signaling interact and contribute to the pathophysiology of schizophrenia, which is particularly relevant for the hippocampus where diverse expression of serotonin receptors is noted. Hippocampal atrophy is a well-established feature of schizophrenia, with select subfields hypothesized as particularly vulnerable due to variation in glutamate receptor densities. We investigated hippocampal anomalies in first-episode psychosis (FEP) in relation to receptor distributions by leveraging 4 sources of data: (1) ultra high-field (7-Tesla) structural neuroimaging, and (2) proton magnetic resonance spectroscopy (1H-MRS) of glutamate from 27 healthy and 41 FEP subjects, (3) gene expression data from the Allen Human Brain Atlas and (4) atlases of the serotonin receptor system.

Conceptual disorganization and redistribution of resting-state cortical hubs in untreated first-episode psychosis: A 7T study.

Network-level dysconnectivity has been studied in positive and negative symptoms of schizophrenia. Conceptual disorganization (CD) is a symptom subtype that predicts impaired real-world functioning in psychosis. Systematic reviews have reported aberrant connectivity in formal thought disorder, a construct related to CD.

Counteracting Effects of Glutathione on the Glutamate-Driven Excitation/Inhibition Imbalance in First-Episode Schizophrenia: A 7T MRS and Dynamic Causal Modeling Study.

Oxidative stress plays a key role in the pathophysiology of schizophrenia. While free radicals produced by glutamatergic excess and oxidative metabolism have damaging effects on brain tissue, antioxidants such as glutathione (GSH) counteract these effects. The interaction between glutamate (GLU) and GSH is centered on N-Methyl-D-aspartate (NMDA) receptors.

MicroRNA-9 Fine-Tunes Dendritic Cell Function by Suppressing Negative Regulators in a Cell-Type-Specific Manner.

Dendritic cells, cells of the innate immune system, are found in a steady state poised to respond to activating stimuli. Once stimulated, they rapidly undergo dynamic changes in gene expression to adopt an activated phenotype capable of stimulating immune responses. We find that the microRNA miR-9 is upregulated in both bone marrow-derived DCs and conventional DC1s but not in conventional DC2s following stimulation.

Glutamate and Dysconnection in the Salience Network: Neurochemical, Effective Connectivity, and Computational Evidence in Schizophrenia.

Background: Functional dysconnection in schizophrenia is underwritten by a pathophysiology of the glutamate neurotransmission that affects the excitation-inhibition balance in key nodes of the salience network. Physiologically, this manifests as aberrant effective connectivity in intrinsic connections involving inhibitory interneurons. In computational terms, this produces a pathology of evidence accumulation and ensuing inference in the brain.

Early treatment response in first episode psychosis: a 7-T magnetic resonance spectroscopic study of glutathione and glutamate.

Early response to antipsychotic medications is one of the most important determinants of later symptomatic and functional outcomes in psychosis. Glutathione and glutamate have emerged as promising therapeutic targets for patients demonstrating inadequate response to dopamine-blocking antipsychotics. Nevertheless, the role of these neurochemicals in the mechanism of early antipsychotic response remains poorly understood.