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Differential expression of NPAS4 in the dorsolateral prefrontal cortex following opioid overdose

David W Sosnowski1, Andrew E Jaffe1,2, Ran Tao2

  • 1Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, 624 N. Broadway, Hampton House, Baltimore, MD 21205, United States.

Drug and Alcohol Dependence Reports
|February 27, 2023
PubMed
Abstract

Insights

Opioid overdose alters gene expression in the human brain. The gene NPAS4 was significantly downregulated in individuals who died from opioid intoxication, suggesting a role in opioid-related outcomes.

Area of Science:

  • Neuroscience
  • Genomics
  • Toxicology

Background:

  • Preclinical models show neurobiological changes in opioid abuse.
  • Human brain gene expression studies, especially after fatal overdose, are lacking.
  • Understanding gene expression in opioid intoxication is crucial.

Purpose of the Study:

  • To compare gene expression in the dorsolateral prefrontal cortex (DLPFC) between individuals who died from acute opioid intoxication and matched controls.
  • To identify specific genes and pathways affected by fatal opioid overdose.

Main Methods:

  • Utilized whole transcriptome RNA-sequencing on postmortem DLPFC samples from 153 individuals.
  • Included 72 opioid intoxication, 53 psychiatric, and 28 normal control samples.
  • Applied differential expression analysis (limma-voom), weighted correlation network analysis, and gene set enrichment analysis.

Main Results:

  • Identified two differentially expressed genes in opioid samples versus controls.
  • The gene NPAS4 was significantly downregulated (log2FC = -2.47, adj. p = .049) in opioid overdose cases.
  • Weighted correlation network analysis revealed 15 gene modules associated with opioid overdose, but no specific hub genes or enriched pathways were identified.

Conclusions:

  • Preliminary evidence suggests NPAS4 is implicated in opioid overdose.
  • Further research is necessary to elucidate the role of NPAS4 in opioid abuse and its consequences.
  • This study highlights the need for comprehensive human brain gene expression analysis in fatal opioid overdose.

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