TY - JOUR
T1 - Impaired verbal memory function is related to anterior cingulate glutamate levels in schizophrenia
T2 - findings from the STRATA study
AU - Griffiths, Kira
AU - Egerton, Alice
AU - Millgate, Edward
AU - Anton, Adriana
AU - Barker, Gareth J
AU - Deakin, Bill
AU - Drake, Richard
AU - Eliasson, Emma
AU - Gregory, Catherine J
AU - Howes, Oliver D
AU - Kravariti, Eugenia
AU - Lawrie, Stephen M
AU - Lewis, Shôn
AU - Lythgoe, David J
AU - Murphy, Anna
AU - McGuire, Philip
AU - Semple, Scott
AU - Stockton-Powdrell, Charlotte
AU - Walters, James T R
AU - Williams, Stephen R
AU - MacCabe, James H
N1 - Funding Information:
This research was supported by the Medical Research Council (MRC) UK, Stratified Medicines Initiative, reference MR/L011794/1 ‘STRATA’. Research at the London site was supported by the Department of Health via the National Institute for Health Research (NIHR) Specialist Biomedical Research Centre for Mental Health award to South London and Maudsley NHS Foundation Trust (SLaM) and the Institute of Psychiatry, Psychology and Neuroscience at King’s College London. K.G. is in receipt of a PhD studentship funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health and Social Care.
Publisher Copyright:
© 2022, The Author(s).
PY - 2022/7/12
Y1 - 2022/7/12
N2 - Impaired 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.
AB - Impaired 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.
UR - http://www.scopus.com/inward/record.url?scp=85134224266&partnerID=8YFLogxK
U2 - 10.1038/s41537-022-00265-5
DO - 10.1038/s41537-022-00265-5
M3 - Article
C2 - 35853881
VL - 8
SP - 60
JO - Schizophrenia
JF - Schizophrenia
IS - 1
M1 - 60
ER -