Schizophrenia: a disorder of broken brain bioenergetics

Henkel, Nicholas D.;Wu, Xiajoun;O'Donovan, Sinead M.;Devine, Emily A.;Jiron, Jessica M.;Rowland, Laura M.;Sarnyai, Zoltan;Ramsey, Amy J.;Wen, Zhexing;Hahn, Margaret K.;McCullumsmith, Robert E.

Zoltan Sarnyai

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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Molecular Psychiatry

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1476-5578

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Nature Publishing Group

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DOI

10.1038/s41380-022-01494-x