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Related Experiment Video

Updated: Aug 24, 2025

Biomarkers in an Animal Model for Revealing Neural, Hematologic, and Behavioral Correlates of PTSD
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PTSD, major depression, and advanced transcriptomic age in brain tissue.

Xiang Zhao1,2,3, Mark W Logue1,2,4,5, Sage E Hawn1,2

  • 1National Center for PTSD at VA Boston Healthcare System, Massachusetts, Boston, USA.

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|October 25, 2022
PubMed
Summary

Psychiatric disorders like PTSD and MDD are linked to accelerated brain aging, particularly in the ventromedial prefrontal cortex. This accelerated aging involves inflammation and immune dysregulation, potentially impacting the blood-brain barrier.

Keywords:
PTSDRNAaccelerated aginginflammationmajor depressiontranscriptomic age

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Area of Science:

  • Neuroscience
  • Genetics
  • Psychiatry

Background:

  • Psychiatric disorders are linked to advanced epigenetic age.
  • The relationship between psychiatric disorders and brain transcriptome aging remains understudied.
  • This study investigates transcriptomic age in relation to major psychiatric disorders.

Purpose of the Study:

  • To examine transcriptomic age using an RNA-based algorithm (RNAAgeCalc).
  • To assess associations between posttraumatic stress disorder (PTSD), major depressive disorder (MDD), and alcohol use disorder with age-adjusted RNA age residuals.
  • To analyze these associations in three specific brain regions: dorsolateral prefrontal cortex, ventromedial prefrontal cortex (vmPFC), and motor cortex.

Main Methods:

  • Utilized RNA sequencing on postmortem brain tissue from 94 individuals (59% male) from the VA National PTSD Brain Bank.
  • Applied linear models to analyze associations between psychiatric diagnoses and RNA age residuals.
  • Conducted enrichment analysis on differentially expressed genes within the RNAAgeCalc algorithm.

Main Results:

  • Diagnoses of PTSD and/or MDD were positively associated with RNA age residuals in the vmPFC (p-adj = 0.012).
  • Three genes (KCNJ16, HYAL2, CEBPB) within the RNAAgeCalc algorithm were differentially expressed in association with PTSD/MDD in vmPFC.
  • Inflammatory and immune-related pathways were overrepresented among genes associated with PTSD/MDD in vmPFC. Endothelial and mural cells were negatively associated with RNA age residuals and PTSD/MDD in vmPFC.

Conclusions:

  • Findings underscore the role of inflammation and immune dysregulation in psychopathology and accelerated cellular aging.
  • Suggests that blood-brain barrier degradation may contribute to stress-related accelerated brain aging.
  • Highlights the vmPFC as a key region in the relationship between psychiatric disorders and brain aging.