Abstract

Purpose:Schizophrenia is a psychiatric disorder characterized by disordered thoughts, abnormal social behaviors, flat affect, and auditory or visual hallucinations. The current study aims to investigate alterations in brain metabolism in patients near the onset of psychosis (early‐phase psychosis, EPP), to characterize abnormalities during the early stages of schizophrenia. To this end, we used magnetic resonance imaging (MRI) and spectroscopy (MRS) to measure metabolite levels and subsequently monitor the effect of treatment with N‐acetylcysteine (NAC).Methods:Here we report on the cross‐sectional comparison at the baseline scan between 13 healthy controls (mean age = 21.5 yrs) and 28 EPP patients (mean age = 23.9 yrs), within three years of psychotic illness onset. Metabolite levels of glutamine + glutamate (Glx), N‐acetylaspartate (NAA), creatine (Cre), and myo‐inositol (mI) were measured on a Siemens 3T whole‐body scanner with MRS voxels placed in the frontal lobe (size = 2×2×2 cm3; TE = 30ms; TA = 4min). Metabolite levels were quantified using LCModel V6.2‐0R, scaled to the internal water signal, and reported in institutional units (i.u.). Comparison of NAA, Cre and Glx levels between the two groups was performed using two‐tailed unpaired t‐tests.Results:A significant decrease of Glx concentration in FEP patients was found (patients: 4.1±1.4 i.u.; controls: 5.2 ± 0.2 i.u.; p=0.04). No significant differences were found at baseline in Cre nor NAA concentrations.Conclusion:Significant decreases in Glx were observed in the frontal lobe of the FEP patients. This decrease supports prior research on schizophrenia in similar cortical regions. The alteration in frontal Glx levels may be involved in the behavioral and cognitive abnormalities. Future steps include investigating the effect of NAC vs. placebo treatment on reversing this decrease in Glx in EPP patients over a 12‐month period.This project is supported by the Stanley Medical Research Institute.

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