Neurometabolic correlates of 6 and 16 weeks of treatment with risperidone in medication-naive first-episode psychosis patients

Abstract

Antipsychotic medications are the cornerstone of treatment in schizophrenia spectrum disorders. In first-episode psychosis, the recommended time for an antipsychotic medication trial is up to 16 weeks, but the biological correlates of shorter and longer antipsychotic treatment trials in these cohorts remain largely unknown. We enrolled 29 medication-naive first-episode patients (FEP) and 22 matched healthy controls (HC) in this magnetic resonance spectroscopy (MRS) study, examining the levels of combined glutamate and glutamine (commonly referred to as Glx) in the bilateral medial prefrontal cortex (MPFC) with a PRESS sequence (TR/TE = 2000/80 ms) before initiation of antipsychotic treatment, after 6 and 16 weeks of treatment with risperidone. Data were quantified in 18 HC and 20 FEP at baseline, for 19 HC and 15 FEP at week 6, and for 14 HC and 16 FEP at week 16. At baseline, none of the metabolites differed between groups. Metabolite levels did not change after 6 or 16 weeks of treatment in patients. Our data suggest that metabolite levels do not change after 6 or 16 weeks of treatment with risperidone in FEP. It is possible that our choice of sequence parameters and the limited sample size contributed to negative findings reported here. On the other hand, longer follow-up may be needed to detect treatment-related metabolic changes with MRS. In summary, our study adds to the efforts in better understanding glutamatergic neurometabolism in schizophrenia, especially as it relates to antipsychotic exposure.

Fig. 1. Illustration of voxel placement and example spectrum.

a Voxel placement in the medial prefrontal cortex (2.0 × 2.0 × 2.0 cm). b Example spectra. The black line represents averaged spectra, the red line is an overlay of the spectral fit, the bottom line is the residual. Cho choline, Cr creatine, Glx glutamate + glutamine, NAA N-acetyl-aspartate, ppm parts per million.

Fig. 2. Neurometabolite measurements.

Dots represent individual measurements, lines represent group means. Glx, glutamate + glutamine; base, baseline measurements; wk 6; measurements at week 6; wk 16, measurements at week 16.