Schizophrenia: a Disorder of Broken Brain Bioenergetics

Overview

Journal Mol Psychiatry

Specialties Molecular Biology
Psychiatry

Date 2022 Mar 10

PMID 35264726

Authors

Nicholas D Henkel

Xiajoun Wu

Sinead M ODonovan

Emily A Devine

Jessica M Jiron

Laura M Rowland

Zoltan Sarnyai

Amy J Ramsey

Zhexing Wen

Margaret K Hahn

Robert E McCullumsmith

Affiliations

Soon will be listed here.

Abstract

A substantial and diverse body of literature suggests that the pathophysiology of schizophrenia is related to deficits of bioenergetic function. While antipsychotics are an effective therapy for the management of positive psychotic symptoms, they are not efficacious for the complete schizophrenia symptom profile, such as the negative and cognitive symptoms. In this review, we discuss the relationship between dysfunction of various metabolic pathways across different brain regions in relation to schizophrenia. We contend that several bioenergetic subprocesses are affected across the brain and such deficits are a core feature of the illness. We provide an overview of central perturbations of insulin signaling, glycolysis, pentose-phosphate pathway, tricarboxylic acid cycle, and oxidative phosphorylation in schizophrenia. Importantly, we discuss pharmacologic and nonpharmacologic interventions that target these pathways and how such interventions may be exploited to improve the symptoms of schizophrenia.

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