The effect of antipsychotics on glutamate levels in the anterior cingulate cortex and clinical response: A 1 H-MRS study in first-episode psychosis patients.

Introduction: Glutamatergic dysfunction is implicated in the pathophysiology of schizophrenia. It is unclear whether glutamatergic dysfunction predicts response to treatment or if antipsychotic treatment influences glutamate levels. We investigated the effect of antipsychotic treatment on glutamatergic levels in the anterior cingulate cortex (ACC), and whether there is a relationship between baseline glutamatergic levels and clinical response after antipsychotic treatment in people with first episode psychosis (FEP).
Materials and Methods: The sample comprised 25 FEP patients; 22 completed magnetic resonance spectroscopy scans at both timepoints. Symptoms were assessed using the Positive and Negative Syndrome Scale (PANSS).
Results: There was no significant change in glutamate [baseline 13.23 ± 2.33; follow-up 13.89 ± 1.74; t(21) = -1.158, p = 0.260], or Glx levels [baseline 19.64 ± 3.26; follow-up 19.66 ± 2.65; t(21) = -0.034, p = 0.973]. There was no significant association between glutamate or Glx levels at baseline and the change in PANSS positive (Glu r = 0.061, p = 0.777, Glx r = -0.152, p = 0.477), negative (Glu r = 0.144, p = 0.502, Glx r = 0.052, p = 0.811), general (Glu r = 0.110, p = 0.607, Glx r = -0.212, p = 0.320), or total scores (Glu r = 0.078, p = 0.719 Glx r = -0.155, p = 0.470).
Conclusion: These findings indicate that treatment response is unlikely to be associated with baseline glutamatergic metabolites prior to antipsychotic treatment, and there is no major effect of antipsychotic treatment on glutamatergic metabolites in the ACC.
Competing Interests: OH was a part-time employee of H. Lundbeck A/S and has received investigator-initiated research funding from and/or participated in advisory/speaker meetings organised by Angellini, Autifony, Biogen, Boehringer-Ingelheim, Eli Lilly, Heptares, Global Medical Education, Invicro, Jansenn, Lundbeck, Neurocrine, Otsuka, Sunovion, Rand, Recordati, Roche, and Viatris/Mylan. Neither OH or his family have holdings/a financial stake in any pharmaceutical company. OH has a patent for the use of dopaminergic imaging. RM has received honoraria for non-promotional talks for Janssen, Sunovian, Otsuka, Lundbeck. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(Copyright © 2022 Zahid, McCutcheon, Borgan, Jauhar, Pepper, Nour, Rogdaki, Osugo, Murray, Hathway, Murray and Howes.)