Abstract
Early response to antipsychotic medications is one of the most important determinants of later symptomatic and functional outcomes in psychosis. Glutathione and glutamate have emerged as promising therapeutic targets for patients demonstrating inadequate response to dopamine-blocking antipsychotics. Nevertheless, the role of these neurochemicals in the mechanism of early antipsychotic response remains poorly understood. Using a longitudinal design and ultrahigh field 7-T magnetic resonance spectroscopy (MRS) protocol in 53 subjects, we report the association between dorsal anterior cingulate cortex glutamate and glutathione, with time to treatment response in drug naive (34.6% of the sample) or minimally medicated first episode patients with schizophreniform disorder, schizophrenia, and schizoaffective disorder. Time to response was defined as the number of weeks required to reach a 50% reduction in the PANSS-8 scores. Higher glutathione was associated with shorter time to response (F = 4.86, P = 0.017), while higher glutamate was associated with more severe functional impairment (F = 5.33, P = 0.008). There were no significant differences between patients and controls on measures of glutamate or glutathione. For the first time, we have demonstrated an association between higher glutathione and favorable prognosis in FEP. We propose that interventions that increase brain glutathione levels may improve outcomes of early intervention in psychosis.
Highlights
Treatment response has been identified as one of the most robust predictors of longer-term clinical outcomes in Supplementary information The online version of this article contains supplementary material, which is available to authorized users.London, ON, Canada 5 Lawson Health Research Institute, London, ON, Canada 6 Department of Diagnostic Imaging, St
The effects of recreational substance use and types of antipsychotics are presented in the Supplementary. This is the first study to use ultrahigh-field 7T magnetic resonance spectroscopy (MRS) to investigate the role of glutamate and GSH in early treatment response, and the first 7T MRS study on minimally medicated first episode of psychosis (FEP) subjects
A more recent study [23] included FEP subjects with up to 2 years of illness duration, while we recruited all subjects during the acute first episode
Summary
ON, Canada 5 Lawson Health Research Institute, London, ON, Canada 6 Department of Diagnostic Imaging, St. Joseph’s Health Care. London, ON, Canada schizophrenia [1]. Lack of early response appears to be strongly indicative of subsequent nonresponse [2], failure to achieve remission [3], and higher rates of treatment discontinuation [4]. One third of patients with schizophrenia are considered to be treatment resistant [5], with the majority of these (23–34%) failing to respond appreciably to dopamine-blocking antipsychotic medications from their first episode of psychosis (FEP) [6, 7]. The neurochemical mechanism of early response is poorly understood, precluding efforts to prevent or reduce the rates of treatment failure and persistent disability
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