Glutamatergic neurotransmission in schizophrenia: a systematic review protocol of 1H-MRS studies throughout phenotypic stages of schizophrenia

Schizophrenia is a significant mental health condition involving the dysregulation of multiple neurological pathways in its pathophysiology. The glutamate hypothesis for schizophrenia suggests a dysfunctional glutamatergic system throughout the varying phenotypic stages of schizophrenia – i.e. first-episode psychosis, chronic schizophrenia, and treatment-resistant schizophrenia. In this systematic review protocol (based on PRSIMA-P guidelines), we outline an approach to explore the relationship between the levels of glutamate, glutamine, and the glutamate-to-glutamine ratio and the varying phenotypic stages of schizophrenia. Furthermore, the protocol proposes to review the empirical magnetic resonance spectroscopy (1H-MRS) literature to better understand the association between these changes in the above clinical subgroups and their neuroanatomical correlates.