Glutamatergic Modulation of Brain Function in Psychosis: A Systematic Review of Neuroimaging Studies

This is the authors' abstract. We don't add key points for this paper.

H-MRS suggests that sarcosine, N-acetylcysteine, and riluzole reduce glutamate concentrations in frontal and hippocampal regions, but clinical outcomes have not been investigated. Resting-state and task-based fMRI studies suggest that NMDA receptor modulators may normalize measures of functional dysconnectivity, although effects were often short-lived and did not always correspond to sustained symptom improvements. Similarly, EEG studies consistently identified normalization of mismatch negativity and gamma oscillations, but correlations with symptom or cognitive outcomes were inconsistent. While glutamatergic modulators show measurable effects on brain chemistry and electrophysiology, the relationship to robust, durable clinical benefits remains elusive. Future work should use larger, longer-duration, and multimodal imaging studies to clarify the precise mechanisms, optimal dosing, and the patient subgroups most likely to benefit from glutamatergic interventions in psychosis.