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.

Keywords: MRS; astrocyte; glutamatergic; neuroinflammation; positive symptoms; schizophrenia.

Fig. 1.

Neurometabolite levels in patients with first-episode psychosis and healthy controls. Cho, choline-containing compounds; Glu, glutamate; Glx, glutamate + glutamine; mI, myo-inositol; NAA, N-acetylaspartate; *P < .05; **P < .01; ***P < .001.

Fig. 2.

Relationships between myo-inositol levels and positive symptom subscale total (a), hallucinatory behavior (b), and grandiosity (c) scores. PANSS, Positive and Negative Syndrome Scale.

Fig. 3.

Relationships between levels of myo-inositol and choline (a), glutamate and myo-inositol (b), and glutamate and choline (c) in patients with first-episode psychosis and healthy controls.