Frontal neural metabolite changes in schizophrenia and their association with cognitive control: A systematic review

A large proportion of patients with schizophrenia exhibit deficits in cognitive control functions including working memory, processing speed and inhibitory control, which have been associated with frontal brain areas. In this systematic review, we investigated differences between chronic schizophrenia patients, first-episode (FEP) patients and healthy control groups in the neurometabolite levels of GABA, glutamate, glutamine and Glx in frontal brain areas. Additionally, we reviewed correlations between cognitive control functions or negative symptoms and these neurometabolite levels. Several studies reported decreased GABA or glutamate concentrations in frontal lobe areas, particularly in chronic schizophrenia patients, while the results were mixed for FEP patients. Working memory performance and prediction errors have been associated with frontal GABA and glutamate levels, and processing speed with frontomedial GABA levels in chronic patients. The relationship between metabolites and negative symptom severity was somewhat inconsistent. Future studies should take the participants' age, medication status or responsivity, disease stage and precise anatomical location of the voxel into account when comparing neurometabolite levels between schizophrenia patients and healthy controls.