Brain Metabolic Abnormalities in Schizophrenia Patients

Abstract

Introduction

Main schizophrenia symptoms result from abnormalities in brain function, such as hypofrontality and structural deficits on the prefrontal-thalamic-cerebellar circuit, as shown in brain imaging studies in first-episode SCZ patients. Whether metabolic alterations may be underlying these events is being studied thoroughly.

Objectives/aims

To assess brain metabolic disturbances in first episode and/or drug-naïve SCZ patients.

Methods

We conducted a literature review through Pubmed search for MeSH: schizophrenia, metabolism, glucose, insulin, brain. Controlled studies on first episode and/or drug-naïve SCZ patients were included.

Results

Lower metabolic activity in the frontal regions of the brain is associated to an increase in norepinephrine transmission and decrease in dopaminergic transmission with reduced dopamine efflux in the frontal cortex. This seems to lead to cellular changes resulting in resulting lower blood flow and glucose demand. Molecular analysis of postmortem SCZ patients’ brains has indicated alterations in glucose metabolism and insulin signalling pathways, showing evidence for prefrontal cortex decreased expression of glucose metabolism, namely glycolytic enzymes such as glyceraldehyde 3-phosphate dehydrogenase, hexokinase, phosphoglycerate mutase, enolase and pyruvate kinase and decreased levels and phosphorylation of the insulin receptor and insulin signalling proteins AKT1 and GSK3β. Significantly elevated glucose concentrations in cerebrospinal fluid were observed in SCZ patients, but with no serum levels differences. A SCZ brain specific increased glucose could be explained by preferential utilization of lactate, predominantly produced by astrocytes, over glucose as an energy substrate.

Conclusions

Abnormalities in brain glucose metabolism and insulin signalling seem to appear in early stages of SCZ, suggesting a role in SCZ onset and pathophysiology.

Disclosure of interest

The authors have not supplied their declaration of competing interest.