P381. The ATPome is a Key Player in the Pathophysiology of Major Depressive Disorder and Schizophrenia

Xiaojun Wu, Xiaolu Zhang, Rammohan Shukla, Alex Joyce, Hunter Eby, Robert McCullumsmith, Sinead O'Donovan

Research output: Contribution to journalMeeting Abstract

Abstract

Background
The ATPome describes the complement of protein enzymes that require ATP, the brains primary energy carrier, to carry out almost all essential cellular functions. The ATPome is composed of enzymes including ATPases and kinases, whose dysfunction is widely reported in major depressive disorder (MDD) and schizophrenia (SCZ). To assess the role of ATPome dysfunction in the pathophysiology of these disorders, we carried out in silico analysis of ATPome-related gene expression in postmortem neuropsychiatric transcriptomic datasets.
Methods
We analyzed 24 publicly available MDD (n=10; male and female) and SCZ (n=14, male and female) transcriptomic datasets. Two ATPome targeting gene lists were prepared, one curated from the Gene Ontology resource and one experimentally demonstrated. Gene enrichment analysis, and pathway enrichment analysis and clustering (parent-child analysis) was conducted.
Results
Significantly altered ATPome genes (p<0.05) represented approximately 15-25% of all differentially expressed genes in MDD and SCZ datasets in males and females, confirming dysregulation of the ATPome in these neuropsychiatric disorders at the transcript level. Pathway analysis identified significant enrichment (FDR <0.01) of biological pathways associated with both upregulated genes and downregulated genes in male SCZ datasets but not female SCZ datasets, where pathway enrichment was associated with downregulated genes only. Conversely, significantly more enriched pathways were identified in male MDD datasets, including metabolic and stress response pathway clusters, compared to females.
Conclusions
These findings support significant sex-differences in neuropsychiatric conditions, particularly in energy utilization. They further suggest that ATP availability is altered in these illnesses and may contribute to the pathophysiological processes underlying MDD and SCZ.
Original languageEnglish (Ireland)
JournalBiological Psychiatry
Volume91
Issue number9_S241
Publication statusPublished - 1 May 2022

Fingerprint

Dive into the research topics of 'P381. The ATPome is a Key Player in the Pathophysiology of Major Depressive Disorder and Schizophrenia'. Together they form a unique fingerprint.

Cite this