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Brain region-specific alterations of RNA editing in PDE8A mRNA in suicide decedents

Fabrice Chimienti1, Laurent Cavarec2, Laurent Vincent3

  • 1ALCEDIAG/ Sys2Diag, CNRS UMR 9005, Parc Euromédecine, Montpellier, France. fabrice.chimienti@alcediag-alcen.com.

Translational Psychiatry
|February 17, 2019
PubMed

Insights

Major depressive disorder (MDD) is linked to reduced phosphodiesterase 8A (PDE8A) in the brain. RNA editing differences in PDE8A were found between control and depressed individuals, suggesting a potential biomarker for suicide risk.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Psychiatry

Background:

  • Phosphodiesterases (PDEs) regulate crucial cellular processes including signal transduction, inflammation, memory, and cognition.
  • A significant decrease in phosphodiesterase 8A (PDE8A) expression is observed in the temporal cortex of major depressive disorder (MDD) patients.
  • RNA editing, specifically A-to-I modifications, plays a role in gene expression regulation within the brain.

Purpose of the Study:

  • To investigate the mRNA editing profile of PDE8A in distinct neocortical regions of the brain.
  • To compare PDE8A mRNA editing patterns between non-psychiatric controls and individuals with major depressive disorder who died by suicide.
  • To identify potential brain-based biomarkers related to immune response and suicide.

Main Methods:

  • Utilized capillary electrophoresis single-stranded conformational polymorphism (CE-SSCP) to analyze PDE8A mRNA editing.
  • Examined PDE8A mRNA editing in the dorsolateral prefrontal cortex (BA9) and anterior cingulate cortex (BA24).
  • Compared editing profiles in a cohort of drug-free controls and depressed suicide decedents.

Main Results:

  • Identified the complete PDE8A mRNA editing profile in the brain, including two novel editing sites.
  • Observed distinct regional differences in PDE8A mRNA editing between the dorsolateral prefrontal cortex and anterior cingulate cortex.
  • Found significant intra-regional differences in PDE8A mRNA editing between control and depressed suicide groups, capable of discriminating between the populations.

Conclusions:

  • PDE8A mRNA editing patterns in the brain show regional specificity and are altered in major depressive disorder and suicide.
  • The findings highlight the involvement of immune/inflammatory pathways in MDD and suicide.
  • This study establishes a link between peripheral RNA modifications and brain RNA editing, suggesting PDE8A editing as a potential immune-related brain marker for suicide and a possible blood-based biomarker for predicting suicidal behavior.

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