SA83. Brain Glutamate Levels and Antipsychotic Response in Schizophrenia

Abstract

Background: There is considerable interest in identifying biomarkers of antipsychotic response in schizophrenia, and brain glutamate is one key candidate. Methods: In a series of 1H-MRS studies, we have investigated the relationship between brain glutamate and antipsychotic response. This includes cross-sectional studies in patients with early psychosis,1 and chronic schizophrenia.2,3 Longitudinally, within the OPTiMiSE consortium, we examined whether glutamate levels in first-episode psychosis (FEP; n = 72, <2 weeks antipsychotic medication) predict psychopathology after subsequent administration of oral amisulpride for 4 weeks. Finally, in an ongoing study in treatment-resistant schizophrenia, we investigate whether glutamate levels prior to clozapine initiation predict the degree of symptomatic response after 12 weeks of clozapine treatment. Results: The cross-sectional study in early psychosis1 found elevated glutamate in the anterior cingulate cortex (ACC) in patients who had reached remission compared to those who had not (T(30) = 3.02; P = .005). ACC glutamate level was positively associated with the severity of negative symptoms (r = .42; P = .017) and negatively associated with of global functioning (r = .47; P = .007). Our first cross-sectional study in chronic schizophrenia2 detected an elevation in ACC glutamate in treatment-resistant schizophrenia (TRS) compared to healthy volunteers (T(14) = 2.80, P = 0.01), which was not apparent in treatment responders (T(16) = 0.29, P = .77). The subsequent larger study3 found higher ACC glutamate levels in TRS than in treatment-responsive patients (T(35) = 2.34, P = .025). In the OPTiMiSE FEP cohort at baseline (prior to amisulpride treatment), ACC glutamate was positively correlated with the PANSS general score (r = .26; P = .03) and negatively correlated with the personal and social performance (PSP) score, (r = −.34; P = .006). Baseline glutamate in the ACC (r = −.38; P = .004) and thalamus (r = −.42; P = .003) were negatively correlated with PSP score after 4 weeks amisulpride. Baseline thalamic glutamate negatively correlated with the longitudinal reduction in the PANSS positive (r = −.35; P = .009) and total (r = −.28; P = .04) scores after 4 weeks amisulpride. An interim update on the ongoing clozapine study will also be provided. Conclusion: This series of studies has returned consistent findings that elevated ACC glutamate is associated with poor response to antipsychotics, more severe symptoms, and social dysfunction. Brain glutamate may relate to the magnitude of response to subsequent antipsychotic treatment.