Dataset Information

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

ABSTRACT:

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.

SUBMITTER: Zahid U

PROVIDER: S-EPMC9403834 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

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

Zahid Uzma U McCutcheon Robert A RA Borgan Faith F Jauhar Sameer S Pepper Fiona F Nour Matthew M MM Rogdaki Maria M Osugo Martin M Murray Graham K GK Hathway Pamela P Murray Robin M RM Egerton Alice A Howes Oliver D OD

Frontiers in psychiatry 20220811

<h4>Introduction</h4>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 f ...[more]

PMID: 36032237

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Project description:Human connectome studies have provided abundant data consistent with the hypothesis that functional dysconnectivity is predominant in psychosis spectrum disorders. Converging lines of evidence also suggest an interaction between dorsal anterior cingulate cortex (dACC) cortical glutamate with higher-order functional brain networks (FC) such as the default mode (DMN), dorsal attention (DAN), and executive control networks (ECN) in healthy controls (HC) and this mechanism may be impaired in psychosis. Data from 70 antipsychotic-medication naïve first-episode psychosis (FEP) and 52 HC were analyzed. 3T Proton magnetic resonance spectroscopy (1H-MRS) data were acquired from a voxel in the dACC and assessed correlations (positive FC) and anticorrelations (negative FC) of the DMN, DAN, and ECN. We then performed regressions to assess associations between glutamate + glutamine (Glx) with positive and negative FC of these same networks and compared them between groups. We found alterations in positive and negative FC in all networks (HC > FEP). A relationship between dACC Glx and positive and negative FC was found in both groups, but when comparing these relationships between groups, we found contrasting associations between these variables in FEP patients compared to HC. We demonstrated that both positive and negative FC in three higher-order resting state networks are already altered in antipsychotic-naïve FEP, underscoring the importance of also considering anticorrelations for optimal characterization of large-scale functional brain networks as these represent biological processes as well. Our data also adds to the growing body of evidence supporting the role of dACC cortical Glx as a mechanism underlying alterations in functional brain network connectivity. Overall, the implications for these findings are imperative as this particular mechanism may differ in untreated or chronic psychotic patients; therefore, understanding this mechanism prior to treatment could better inform clinicians.Clinical trial registration: Trajectories of Treatment Response as Window into the Heterogeneity of Psychosis: A Longitudinal Multimodal Imaging Study, NCT03442101 . Glutamate, Brain Connectivity and Duration of Untreated Psychosis (DUP), NCT02034253 .

Project description:BackgroundReduced glutamatergic excitability of the anterior cingulate cortex (ACC) has been long suspected in schizophrenia; recent observations support low glutamatergic tone as the primary pathophysiology contributing to subtle early features of this illness, with a secondary disinhibition (higher glutamate tone) resulting in more prominent clinical symptoms later in its course. We sought to investigate whether people with genetic high risk (GHR) for schizophrenia have lower glutamate levels in the ACC than those at later stages of clinical high risk (CHR) and those with first-episode schizophrenia (FES), among whom symptoms are already prominent.MethodsWe recruited people with CHR, GHR, or FES, as well as healthy controls. Using proton magnetic resonance spectroscopy, we determined glutamate levels in the perigenual ACC (pACC) and dorsal ACC (dACC) using a 3 T scanner.ResultsWe recruited 302 people across multiple stages of psychosis, including 63 with CHR, 76 with GHR, and 96 with FES, as well as 67 healthy controls. Those with GHR had lower glutamate levels in the dACC than those with CHR, while those with CHR had higher glutamate levels in the pACC than those with FES. Higher disorganization, but not any other symptom domain, was associated with lower levels of glutamate in the GHR group (dACC and pACC) and in the CHR group (pACC).LimitationsThe cross-sectional design precluded inferences regarding individual clinical trajectory and resolution at 3 T was insufficient to separate spectra of glutamine from glutamate.ConclusionReduced glutamatergic tone among people genetically predisposed to schizophrenia supports diminished excitability as an early feature of schizophrenia, contributing to the subtle symptom of disorganization across high-risk states. Higher glutamate levels become apparent when psychotic symptoms become prominent, possibly as a disinhibitory effect and, at the full-blown stage of psychosis, the relationship between glutamate concentrations and symptoms ceases to be simply linear.

Dataset Information

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

Introduction

Materials and methods

Results

Conclusion

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

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

Introduction

Materials and methods

Results

Conclusion

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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