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.
Highlights
Antipsychotic medications are the foundation of acute and maintenance treatment in schizophrenia spectrum disorders
Sample characteristics and demographics Of the 29 first-episode patients (FEP) enrolled in this study, five dropped before the baseline scans were completed, one was excluded from all analyses due to gross anatomical abnormalities observed at the baseline anatomical scan, five dropped prior to the week 6 scan, and one subject did not tolerate the scan at week 16
magnetic resonance spectroscopy (MRS) data were not obtained for three subjects at baseline, for three subjects at week 6, and for one subject at week 16 in this multimodal neuroimaging study
Summary
Antipsychotic medications are the foundation of acute and maintenance treatment in schizophrenia spectrum disorders. In multi-episode schizophrenia, effectiveness of the medication is typically established within 2–6 weeks of treatment[1,2,3,4,5]. Recommendations for these timeframes as adequate duration of antipsychotic treatment trials are supported by meta-analyses demonstrating that the greatest fraction of antipsychotic response occurs within the first 2 weeks[6,7], and that a substantial proportion of symptom improvement after 1 year has already been achieved within the first 4 weeks[7]. In the context of psychosis, examination of glutamatergic measures are of particular
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