Dysfunction of mitochondria and GABAergic interneurons in the anterior cingulate cortex of individuals with schizophrenia

Mari A. Kondo, Alexis L. Norris, Kun Yang, Madeline Cheshire, Isabelle Newkirk, Xiangning Chen, Koko Ishizuka, Andrew E. Jaffe, Akira Sawa, Jonathan Pevsner

Research output: Contribution to journalArticlepeer-review

Abstract

Here we re-analyze RNA-sequencing data from the anterior cingulate cortex (ACC) of SZ patients using recent methods to improve accuracy and sensitivity of results, such as the quality surrogate variable analysis (qSVA) method and the derfinder R package. We found that genes significantly down-regulated in SZ demonstrated an enrichment for parvalbumin-positive interneurons (FDR < 0.0001). Down-regulated genes were also enriched in oxidative phosphorylation functions (FDR < 0.05). We also addressed whether lifetime exposure to antipsychotics might influence gene expression, highlighting DUSP6, LBH, and NR1D1. Our results support the role of redox imbalance/mitochondrial dysfunction and implicate interneuron subtypes in SZ pathophysiology.

Original languageEnglish (US)
Pages (from-to)67-72
Number of pages6
JournalNeuroscience Research
Volume185
DOIs
StatePublished - Dec 2022

Keywords

  • Anterior cingulate cortex
  • Gene expression
  • Mitochondrial dysfunction
  • Quality surrogate variable analysis
  • Redox imbalance
  • Schizophrenia

ASJC Scopus subject areas

  • General Neuroscience

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