Neurometabolic abnormalities in the associative striatum in antipsychotic-naïve first episode psychosis patients

Abstract

Schizophrenia is a chronic, often progressive, disorder. Understanding the underlying neurobiology present in the early stages of the illness is as a pivotal step in designing targeted interventions aimed at arresting disease progression. The aim of our study was to examine neurometabolic changes in the dopamine rich associative striatum in medication-naïve first episode psychosis (FEP). We quantified neurometabolites in 14 FEP and 18 healthy controls (HC) matched on key demographic characteristics. Spectra from the voxel in the left associative striatum were acquired using a PRESS sequence (TR/TE = 2000/80 ms; 512 averages). MRS data were quantified in the time domain with AMARES in jMRUI. Choline was significantly elevated in FEP compared to HC. No significant alterations in other metabolites were observed. We did not observe correlations between metabolite levels and clinical characteristics in FEP. Here, we demonstrated elevated choline and a disruption of the relationship between N-acetyl-aspartate and Glx (glutamate + glutamine) in medication-naïve FEP patients in the left striatum indicating possible mitochondrial, membrane and glial dysfunction as an underlying pathological phenomenon. In addition, striatal choline shows promise as a biomarker for FEP that may have utility in clinical trials investigating target engagement in experimental regimens.

Trial registration: ClinicalTrials.gov NCT02034253.

Keywords: Antipsychotic; Choline; Glutamate; Magnetic resonance spectroscopy; Striatum.

Conflict of interest statement

Conflict of interest

ACL has received an investigator initiated grant from Janssen Pharmaceuticals. All other authors declare no conflicts of interest, including relevant financial interests, activities, relationships, and affiliations.

Copyright © 2018 Elsevier B.V. All rights reserved.

Figures

Figure 1:

Illustration of voxel placement and example spectrum. A. Placement of the spectroscopy voxel in the left associative striatum. Image is displayed in radiological convention (right side of image is subject’s left side). B. Top: The black line is a spectrum (512 averages) obtained from the left associative striatum voxel, the red line is an overlay of spectral fit. Bottom: Residual. Cho, choline; Cr, creatine; Glx, glutamate + glutamine; NAA, N-acetylaspartate; ppm, parts per million.

Figure 2:

Comparison of Choline levels measured in the left associative striatum in healthy controls (HC) and first episode psychosis (FEP) subjects. Triangles represent individual measurements.

Figure 3:

Partial correlations between Glx (glutamate+glutamine) and NAA (N-acetyl-aspartate) in the left associate striatum. Left panel shows a correlation between metabolites in healthy controls (r= 0.85; n=16), right shows a lack of correlation between metabolites in first episode psychosis patients (r = 0.38; n=14), correlations were significantly different between groups (z= 2.05; p= 0.04). Plotted Glx values are the log transform of individual values.