The role of glutamate and GABA in cognitive dysfunction in schizophrenia and mood disorders – A systematic review of magnetic resonance spectroscopy studies

Abstract

Epidemiologic, genetic, and neurobiological studies suggest considerable overlap between schizophrenia and mood disorders. Importantly, both disorders are associated with a broad range of cognitive deficits as well as altered glutamatergic and GABAergic neurometabolism. We conducted a systematic review of magnetic resonance spectroscopy (MRS) studies investigating the relationship between glutamatergic and GABAergic neurometabolites and cognition in schizophrenia spectrum disorders and mood disorders. A literature search in Pubmed of studies published before April 15, 2019 was conducted and 37 studies were deemed eligible for systematic review. We found that alterations in glutamatergic and GABAergic neurotransmission have been identified relatively consistently in both schizophrenia and mood disorders. However, because of the vast heterogeneity of published studies in terms of illness stage, medication exposure, MRS acquisition parameters and data post-processing strategies, we still do not understand the relationship between those neurotransmitters and cognitive dysfunction in mental illness, which is a critical initial step for rational drug development. Our findings emphasize the need for coordinated multi-center studies that characterize cognitive function and its biological substrates in large and well-defined clinical populations, using harmonized imaging sequences and analytical methods with the goal to elucidate the underlying pathophysiological mechanisms and to inform future clinical trials.