Magnetic resonance spectroscopic evidence of increased choline in the dorsolateral prefrontal and visual cortices in recent onset schizophrenia

Smucny, Jason; Carter, Cameron S.; Maddock, Richard J.

doi:10.1016/j.neulet.2021.136410

Cited by 7 publications

(3 citation statements)

References 33 publications

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“…The dopamine and glutamate hypotheses are not mutually exclusive, however, as dopamine neurones interact closely with glutamate neurones. Similar to the findings of brain MRS studies examining glutamate in depression, studies in schizophrenia have also not historically been concordant [120]. Some meta-analyses have indicated significant declines in glutamate in the mPFC, whilst others have concluded non-significant glutamate changes in the same region [121,122].…”

Section: The Glutamate Hypothesis Of Schizophreniamentioning

confidence: 80%

Emerging Evidence for the Widespread Role of Glutamatergic Dysfunction in Neuropsychiatric Diseases

et al. 2022

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The monoamine model of depression has long formed the basis of drug development but fails to explain treatment resistance or associations with stress or inflammation. Recent animal research, clinical trials of ketamine (a glutamate receptor antagonist), neuroimaging research, and microbiome studies provide increasing evidence of glutamatergic dysfunction in depression and other disorders. Glutamatergic involvement across diverse neuropathologies including psychoses, neurodevelopmental, neurodegenerative conditions, and brain injury forms the rationale for this review. Glutamate is the brain’s principal excitatory neurotransmitter (NT), a metabolic and synthesis substrate, and an immune mediator. These overlapping roles and multiple glutamate NT receptor types complicate research into glutamate neurotransmission. The glutamate microcircuit comprises excitatory glutamatergic neurons, astrocytes controlling synaptic space levels, through glutamate reuptake, and inhibitory GABA interneurons. Astroglia generate and respond to inflammatory mediators. Glutamatergic microcircuits also act at the brain/body interface via the microbiome, kynurenine pathway, and hypothalamus–pituitary–adrenal axis. Disruption of excitatory/inhibitory homeostasis causing neuro-excitotoxicity, with neuronal impairment, causes depression and cognition symptoms via limbic and prefrontal regions, respectively. Persistent dysfunction reduces neuronal plasticity and growth causing neuronal death and tissue atrophy in neurodegenerative diseases. A conceptual overview of brain glutamatergic activity and peripheral interfacing is presented, including the common mechanisms that diverse diseases share when glutamate homeostasis is disrupted.

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Section: The Glutamate Hypothesis Of Schizophreniamentioning

confidence: 80%

Emerging Evidence for the Widespread Role of Glutamatergic Dysfunction in Neuropsychiatric Diseases

et al. 2022

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“…However, glutamate, creatine, mayo-inositol, and N -acetylaspartate levels showed no changes in these regions. They also discovered that there is a negative correlation between N -acetylaspartate levels in dorsolateral prefrontal cortex and negative symptoms in schizophrenia ( Smucny et al, 2022 ).…”

Section: Imagingmentioning

confidence: 99%

Neuroimaging in schizophrenia: A review article

et al. 2022

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In this review article we have consolidated the imaging literature of patients with schizophrenia across the full spectrum of modalities in radiology including computed tomography (CT), morphologic magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), magnetic resonance spectroscopy (MRS), positron emission tomography (PET), and magnetoencephalography (MEG). We look at the impact of various subtypes of schizophrenia on imaging findings and the changes that occur with medical and transcranial magnetic stimulation (TMS) therapy. Our goal was a comprehensive multimodality summary of the findings of state-of-the-art imaging in untreated and treated patients with schizophrenia. Clinical imaging in schizophrenia is used to exclude structural lesions which may produce symptoms that may mimic those of patients with schizophrenia. Nonetheless one finds global volume loss in the brains of patients with schizophrenia with associated increased cerebrospinal fluid (CSF) volume and decreased gray matter volume. These features may be influenced by the duration of disease and or medication use. For functional studies, be they fluorodeoxyglucose positron emission tomography (FDG PET), rs-fMRI, task-based fMRI, diffusion tensor imaging (DTI) or MEG there generally is hypoactivation and disconnection between brain regions. However, these findings may vary depending upon the negative or positive symptomatology manifested in the patients. MR spectroscopy generally shows low N-acetylaspartate from neuronal loss and low glutamine (a neuroexcitatory marker) but glutathione may be elevated, particularly in non-treatment responders. The literature in schizophrenia is difficult to evaluate because age, gender, symptomatology, comorbidities, therapy use, disease duration, substance abuse, and coexisting other psychiatric disorders have not been adequately controlled for, even in large studies and meta-analyses.

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“…Cho plays a crucial role in generating membrane phospholipids that are essential in the human brain [6]; an elevated Cho signal is thought to point to an increase in membrane synthesis and turnover [7]. In SCZ, significantly higher levels of Cho have been observed in the dorsolateral prefrontal cortex (DLPFC) of chronic SCZ and first-episode psychosis (FEP) patients compared to healthy control (HC) subjects [8,9]. SCZ patients have also been found to have elevated Cho levels in the left caudate nucleus [10] and insular cortex [11] relative to controls.…”

Section: Introductionmentioning

confidence: 99%

N-Acetylaspartate and Choline Metabolites in Cortical and Subcortical Regions in Clinical High Risk Relative to Healthy Control Subjects: An Exploratory 7T MRSI Study

Mayeli

Janssen

Huston

et al. 2023

IJMS

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N-acetylaspartate (NAA) and choline (Cho) are two brain metabolites implicated in several key neuronal functions. Abnormalities in these metabolites have been reported in both early course and chronic patients with schizophrenia (SCZ). It is, however, unclear whether NAA and Cho’s alterations occur even before the onset of the disorder. Clinical high risk (CHR) individuals are a population uniquely enriched for psychosis and SCZ. In this exploratory study, we utilized 7-Tesla magnetic resonance spectroscopic imaging (MRSI) to examine differences in total NAA (tNAA; NAA + N-acetylaspartylglutamate [NAAG]) and major choline-containing compounds, including glycerophosphorylcholine and phosphorylcholine [tCho], over the creatine (Cre) levels between 26 CHR and 32 healthy control (HC) subjects in the subcortical and cortical regions. While no tCho/Cre differences were found between groups in any of the regions of interest (ROIs), we found that CHR had significantly reduced tNAA/Cre in the right dorsal lateral prefrontal cortex (DLPFC) compared to HC, and that the right DLPFC tNAA/Cre reduction in CHR was negatively associated with their positive symptoms scores. No tNAA/Cre differences were found between CHR and HC in other ROIs. In conclusion, reduced tNAA/Cre in CHR vs. HC may represent a putative molecular biomarker for risk of psychosis and SCZ that is associated with symptom severity.

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Magnetic resonance spectroscopic evidence of increased choline in the dorsolateral prefrontal and visual cortices in recent onset schizophrenia

Cited by 7 publications

References 33 publications

Emerging Evidence for the Widespread Role of Glutamatergic Dysfunction in Neuropsychiatric Diseases

Emerging Evidence for the Widespread Role of Glutamatergic Dysfunction in Neuropsychiatric Diseases

Neuroimaging in schizophrenia: A review article

N-Acetylaspartate and Choline Metabolites in Cortical and Subcortical Regions in Clinical High Risk Relative to Healthy Control Subjects: An Exploratory 7T MRSI Study

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