Meta-analysis of brain samples of individuals with schizophrenia detects down-regulation of multiple ATP synthase encoding genes in both females and males

Noa Katz Shroitman, Assif Yitzhaky, Dorit Ben Shachar, David Gurwitz, Libi Hertzberg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Schizophrenia is a chronic and debilitating mental disorder, with unknown pathophysiology. Converging lines of evidence suggest that mitochondrial functioning may be compromised in schizophrenia. Postmortem brain samples of individuals with schizophrenia showed dysregulated expression levels of genes encoding enzyme complexes comprising the mitochondrial electron transport chain (ETC), including ATP synthase, the fifth ETC complex. However, there are inconsistencies regarding the direction of change, i.e., up- or down-regulation, and differences between female and male patients were hardly examined. We have performed a systematic meta-analysis of the expression of 16 ATP synthase encoding genes in postmortem brain samples of individuals with schizophrenia vs. healthy controls of three regions: Brodmann Area 10 (BA10), BA22/Superior Temporal Gyrus (STG) and the cerebellum. Eight independent datasets were integrated (overall 294brain samples, 145 of individuals with schizophrenia and 149 controls). The meta-analysis was applied to all individuals with schizophrenia vs. the controls, and also to female and male patients vs. age-matched controls, separately. A significant down-regulation of two ATP synthase encoding genes was detected in schizophrenia, ATP5A1 and ATP5H, and a trend towards down-regulation of five further ATP synthase genes. The down-regulation tendency was shown for both females and males with schizophrenia. Our findings support the hypothesis that schizophrenia is associated with reduced ATP synthesis via the oxidative phosphorylation system, which is caused by reduced cellular demand of ATP. Abnormal cellular energy metabolism can lead to alterations in neural function and brain circuitry, and thereby to the cognitive and behavioral aberrations characteristic of schizophrenia.

Original languageEnglish
Pages (from-to)350-359
Number of pages10
JournalJournal of Psychiatric Research
Volume158
DOIs
StatePublished - Feb 2023

Keywords

  • ATP synthase
  • Gene expression
  • Male and female differences
  • Postmortem brain samples
  • Schizophrenia

Fingerprint

Dive into the research topics of 'Meta-analysis of brain samples of individuals with schizophrenia detects down-regulation of multiple ATP synthase encoding genes in both females and males'. Together they form a unique fingerprint.

Cite this