SA84. Proton Magnetic Spectroscopy Shows Elevated Striatal Choline Levels in Drug-Naive Patients With First-Episode Psychosis

摘要

>Background: Cytokines released by microglia has been hypothesized to cause aberrant astrocyte signaling which in turn may result in glutamate dysfunction. Elevated choline is proposed to reflect glial activation. To study our hypothesis that untreated, first-episode psychosis would affect levels of choline and glutamate, we conducted a magnetic resonance spectroscopy study in the striatum. >Methods: We enrolled 19 age, gender, and parental socioeconomic status matched healthy controls (HC) and patients with first-episode psychosis (FEP) as part of our study. One HC and 5 FEP patients who did not have good quality spectral data were not included in the analysis. Imaging was performed on a 3T head-only scanner (Magnetom Allegra, Siemens Medical Solutions, Erlangen, Germany) equipped with a circularly polarized transmit/receive head coil. A series of sagittal, coronal, and axial T1-weighted anatomical scans (gradient-recalled echo sequence, TR/TE = 250/ 3.48ms, flip angle= 70°,5 mm slice thickness,1.5 mm gap,512 × 512 matrix) were acquired for voxel placement. MRS data were collected from a voxel in the left striatum (1.8 × 1.8 × 1.8 cm). Following manual shimming, water-suppressed spectra were acquired using the point-resolved spectroscopy sequence (PRESS; TR/TE= 2000/ 80ms; 1200 Hz spectral bandwidth; 1024 points; number of averages = 512). Eight unsuppressed water averages were also obtained. MRS data were analyzed in jMRUI. Spectra were quantified with respect to water in the time domain using the AMARES algorithm. Exclusion criteria of Creamer Rao Lower Bound >20% was used and had to exclude 2 HC based on CRLB for glutamate. Group differences in metabolites were examined with analysis of covariance (ANCOVA) using disease state as between-group factor and smoking and gray matter fraction as covariates. Positive and negative symptoms were assessed using Brief Psychiatric Rating Scale (BPRS). Partial correlations were used to examine the relationship between BPRS scores and metabolites. >Results: There were no differences between age, sex, and socioeconomic status between patients with FEP and HC. We found elevated choline levels in comparisons between FEP and HC groups, (P = .010 and F = 4.583, FEP mean = 0.235, SD = 0.036, HC mean = 0.200, SD = 0.026), after controlling for packs per day and gray matter fractions. There was no difference between the groups, with respect to other metabolites Glx (glutamate+glutamine), Cr, and NAA. In patients with first-episode psychosis, Glx was negatively correlated with BPRS scale positive symptom (r = −.680, P = .021). >Conclusion: The elevated choline in the FEP group may reflect the increased membrane turn over from glial cells, which supports the hypothesis of neuroinflammation as a possible etiology of schizophrenia. Antipsychotics have shown to inhibit the microglial activation in animal models, making a case for earlier treatment of untreated psychosis to prevent the downstream effects of inflammation.