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Impaired verbal memory function is related to anterior cingulate glutamate levels in schizophrenia: findings from the STRATA study

Abstract:
AbstractImpaired cognition is associated with lower quality of life and poor outcomes in schizophrenia. Brain glutamate may contribute to both clinical outcomes and cognition, but these relationships are not well-understood. We studied a multicentre cohort of 85 participants with non-affective psychosis using proton magnetic resonance spectroscopy. Glutamate neurometabolites were measured in the anterior cingulate cortex (ACC). Cognition was assessed using the Brief Assessment for Cognition in Schizophrenia (BACS). Patients were categorised as antipsychotic responders or non-responders based on treatment history and current symptom severity. Inverted U-shaped associations between glutamate or Glx (glutamate + glutamine) with BACS subscale and total scores were examined with regression analyses. We then tested for an interaction effect of the antipsychotic response group on the relationship between glutamate and cognition. ACC glutamate and Glx had a positive linear association with verbal memory after adjusting for age, sex and chlorpromazine equivalent dose (glutamate, β = 3.73, 95% CI = 1.26–6.20, P = 0.004; Glx, β = 3.38, 95% CI = 0.84–5.91, P = 0.01). This association did not differ between good and poor antipsychotic response groups. ACC glutamate was also positively associated with total BACS score (β = 3.12, 95% CI = 0.01–6.23, P = 0.046), but this was not significant after controlling for antipsychotic dose. Lower glutamatergic metabolites in the ACC were associated with worse verbal memory, and this relationship was independent of antipsychotic response. Further research on relationships between glutamate and cognition in antipsychotic responsive and non-responsive illness could aid the stratification of patient groups for targeted treatment interventions.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/s41537-022-00265-5

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Author
ORCID:
0000-0001-6885-086X
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Author
ORCID:
0000-0003-2939-064X
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ORCID:
0000-0001-5424-8261
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ORCID:
0000-0002-1356-4513
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Author
ORCID:
0000-0002-5214-7421


Publisher:
Nature Research
Journal:
Schizophrenia More from this journal
Volume:
8
Issue:
1
Pages:
60-60
Publication date:
2022-07-12
DOI:
EISSN:
2754-6993
ISSN:
2754-6993


Language:
English
Keywords:
Pubs id:
2359277
Local pid:
pubs:2359277
Source identifiers:
W4285089507
Deposit date:
2026-01-15
ARK identifier:
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