Dataset Information

Decoupling of Brain Temperature and Glutamate in Recent Onset of Schizophrenia: A 7T Proton Magnetic Resonance Spectroscopy Study.

ABSTRACT:

Background

Converging evidence suggests that cerebral metabolic and cellular homeostasis is altered in patients with recent onset of schizophrenia. As a possible marker of metabolic changes that might link to altered neurotransmission, we used proton magnetic resonance spectroscopy to estimate brain temperature, and we evaluated its relationship to a relevant metabolite, glutamate, within this study population.

Methods

Using proton magnetic resonance spectroscopy at 7T, 20 patients with recent onset (≤24 months after first psychotic symptoms) of schizophrenia and 20 healthy control subjects were studied. We measured levels of N-acetylaspartate and glutamate and estimated brain temperature in a noninvasive manner.

Results

Healthy control subjects showed a significant negative correlation between glutamate and brain temperature in the anterior cingulate cortex. In contrast, the physiological correlation between glutamate and brain temperature was lost in patients with recent onset of schizophrenia.

Conclusions

This study supports the hypothesized disrupted relationship between brain metabolism and neurotransmission in patients with recent onset of schizophrenia. The findings include mechanistic implications that are to be followed up in both preclinical and clinical studies.

SUBMITTER: Posporelis S

PROVIDER: S-EPMC5836506 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Publications

Decoupling of Brain Temperature and Glutamate in Recent Onset of Schizophrenia: A 7T Proton Magnetic Resonance Spectroscopy Study.

Posporelis Sotirios S Coughlin Jennifer M JM Marsman Anouk A Pradhan Subechhya S Tanaka Teppei T Wang Hongxing H Varvaris Mark M Ward Rebecca R Higgs Cecilia C Edwards Jamie A JA Ford Candice N CN Kim Pearl K PK Lloyd Ashley M AM Edden Richard A E RAE Schretlen David J DJ Cascella Nicola G NG Barker Peter B PB Sawa Akira A

Biological psychiatry. Cognitive neuroscience and neuroimaging 20170421 3

<h4>Background</h4>Converging evidence suggests that cerebral metabolic and cellular homeostasis is altered in patients with recent onset of schizophrenia. As a possible marker of metabolic changes that might link to altered neurotransmission, we used proton magnetic resonance spectroscopy to estimate brain temperature, and we evaluated its relationship to a relevant metabolite, glutamate, within this study population.<h4>Methods</h4>Using proton magnetic resonance spectroscopy at 7T, 20 patient ...[more]

PMID: 29486866

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Project description:ImportanceProton 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.ObjectiveTo assess the associations of age, symptom severity, level of functioning, and antipsychotic treatment with brain glutamatergic metabolites.Data sourcesThe MEDLINE database was searched to identify journal articles published between January 1, 1980, and June 3, 2020, using the following search terms: MRS or magnetic resonance spectroscopy and (1) schizophrenia or (2) psychosis or (3) UHR or (4) ARMS or (5) ultra-high risk or (6) clinical high risk or (7) genetic high risk or (8) prodrome* or (9) schizoaffective. Authors of 114 1H-MRS studies measuring glutamate (Glu) levels in patients with schizophrenia were contacted between January 2014 and June 2020 and asked to provide individual participant data.Study selectionIn total, 45 1H-MRS studies contributed data.Data extraction and synthesisAssociations of Glu, Glu plus glutamine (Glx), or total creatine plus phosphocreatine levels with age, antipsychotic medication dose, symptom severity, and functioning were assessed using linear mixed models, with study as a random factor.Main outcomes and measuresGlu, Glx, and Cr values in the medial frontal cortex (MFC) and medial temporal lobe (MTL).ResultsIn total, 42 studies were included, with data for 1251 patients with schizophrenia (mean [SD] age, 30.3 [10.4] years) and 1197 healthy volunteers (mean [SD] age, 27.5 [8.8] years). The MFC Glu (F1,1211.9 = 4.311, P = .04) and Glx (F1,1079.2 = 5.287, P = .02) levels were lower in patients than in healthy volunteers, and although creatine levels appeared lower in patients, the difference was not significant (F1,1395.9 = 3.622, P = .06). In both patients and volunteers, the MFC Glu level was negatively associated with age (Glu to Cr ratio, F1,1522.4 = 47.533, P < .001; cerebrospinal fluid-corrected Glu, F1,1216.7 = 5.610, P = .02), showing a 0.2-unit reduction per decade. In patients, antipsychotic dose (in chlorpromazine equivalents) was negatively associated with MFC Glu (estimate, 0.10 reduction per 100 mg; SE, 0.03) and MFC Glx (estimate, -0.11; SE, 0.04) levels. The MFC Glu to Cr ratio was positively associated with total symptom severity (estimate, 0.01 per 10 points; SE, 0.005) and positive symptom severity (estimate, 0.04; SE, 0.02) and was negatively associated with level of global functioning (estimate, 0.04; SE, 0.01). In the MTL, the Glx to Cr ratio was positively associated with total symptom severity (estimate, 0.06; SE, 0.03), negative symptoms (estimate, 0.2; SE, 0.07), and worse Clinical Global Impression score (estimate, 0.2 per point; SE, 0.06). The MFC creatine level increased with age (estimate, 0.2; SE, 0.05) but was not associated with either symptom severity or antipsychotic medication dose.Conclusions and relevanceFindings from this mega-analysis suggest that lower brain Glu levels in patients with schizophrenia may be associated with antipsychotic medication exposure rather than with greater age-related decline. Higher brain Glu levels may act as a biomarker of illness severity in schizophrenia.

Dataset Information

Decoupling of Brain Temperature and Glutamate in Recent Onset of Schizophrenia: A 7T Proton Magnetic Resonance Spectroscopy Study.

Background

Methods

Results

Conclusions

Publications

Decoupling of Brain Temperature and Glutamate in Recent Onset of Schizophrenia: A 7T Proton Magnetic Resonance Spectroscopy Study.

Similar Datasets

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