title: Elevated Myo-Inositol, Choline, and Glutamate Levels in the Associative Striatum of Antipsychotic-Naive Patients With First-Episode Psychosis: A Proton Magnetic Resonance Spectroscopy Study With Implications for Glial Dysfunction.
abstract: Glial disturbances are highly implicated in the pathophysiology of schizophrenia and may be linked with glutamatergic dysregulation. Myo-inositol (mI), a putative marker of glial cells, and choline (Cho), representative of membrane turnover, are both present in larger concentrations within glial cells than in neurons, and their elevation is often interpreted to reflect glial activation. Proton magnetic resonance spectroscopy ((1)H-MRS) allows for the evaluation of mI, Cho, glutamate, glutamate + glutamine (Glx), and N-acetylaspartate (NAA). A collective investigation of these measures in antipsychotic-naive patients experiencing their first nonaffective episode of psychosis (FEP) can improve the understanding of glial dysfunction and its implications in the early stages of schizophrenia. 3-Tesla (1)H-MRS (echo time = 35 ms) was performed in 60 antipsychotic-naive patients with FEP and 60 age- and sex-matched healthy controls. mI, Cho, glutamate, Glx, and NAA were estimated using LCModel and corrected for cerebrospinal fluid composition within the voxel. mI, Cho, and glutamate were elevated in the FEP group. After correction for multiple comparisons, mI positively correlated with grandiosity. The relationships between mI and glutamate, and Cho and glutamate, were more positive in the FEP group. These findings are suggestive of glial activation in the absence of neuronal loss and may thereby provide support for the presence of a neuroinflammatory process within the early stages of schizophrenia. Dysregulation of glial function might result in the disruption of glutamatergic neurotransmission, which may influence positive symptomatology in patients with FEP.
authors: Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada;
authors: Eric
authors: E
authors: Plitman
authors: Laboratory of Experimental Psychiatry, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico; Neuropsychiatry Department, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico; fcamilo@unam.mx.
authors: Camilo
authors: C
authors: de la Fuente-Sandoval
authors: Laboratory of Experimental Psychiatry, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico;
authors: Francisco
authors: F
authors: Reyes-Madrigal
authors: Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada;
authors: Sofia
authors: S
authors: Chavez
authors: Laboratory of Experimental Psychiatry, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico;
authors: Gladys
authors: G
authors: Gómez-Cruz
authors: Laboratory of Experimental Psychiatry, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico; Department of Education, Instituto Nacional de Neurología y Neurocirugía, Mexico City, Mexico;
authors: Pablo
authors: P
authors: León-Ortiz
authors: Multimodal Imaging Group, Research Imaging Centre, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada; Institute of Medical Science, University of Toronto, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Geriatric Mental Health Division, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada; Campbell Institute Research Program, Centre for Addiction and Mental Health, University of Toronto, Toronto, Ontario, Canada.
authors: Ariel
authors: A
authors: Graff-Guerrero
mesh_terms: D000328:Adult; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D002794:Choline / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D007294:Inositol / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism*; D066244:Proton Magnetic Resonance Spectroscopy; D011618:Psychotic Disorders / Q000378:metabolism*; D012559:Schizophrenia / Q000378:metabolism*
chemical_list: D005973:Glutamine; D001224:Aspartic Acid; D018698:Glutamic Acid; D007294:Inositol; C000179:N-acetylaspartate; D002794:Choline
keywords: MRS; astrocyte; glutamatergic; neuroinflammation; positive symptoms; schizophrenia