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Intensified vmPFC surveillance over PTSS under perturbed microRNA-608/AChE interaction.
T Lin1,2, A Simchovitz3, S Shenhar-Tsarfaty3
1The Tel-Aviv Center for Brain Function, Wohl Institute for Advanced Imaging, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel.
Translational Psychiatry
|May 4, 2016
Summary
A specific gene variant (SNP rs17228616) in soldiers may protect against posttraumatic stress symptoms (PTSS) by enhancing brain regulation, despite increased amygdala reactivity to threats.
Area of Science:
- Neuroscience
- Genetics
- Psychiatry
Background:
- Trauma's impact on mental health varies due to unknown genetic and neuronal factors.
- A specific single-nucleotide polymorphism (SNP) rs17228616 in the acetylcholinesterase (AChE) gene influences stress responses.
- This SNP disrupts microRNA (miRNA)-608 regulation, affecting brain AChE, cortisol, and CDC42 levels.
Purpose of the Study:
- To investigate the effect of SNP rs17228616 on posttraumatic stress symptoms (PTSS).
- To examine the influence of this SNP on threat-related brain circuits, specifically amygdala and ventromedial prefrontal cortex (vmPFC) activity.
- To understand the genome-neuronal interactions underlying variable PTSS risk after trauma.
Main Methods:
- Functional magnetic resonance imaging (fMRI) was used to assess brain activity in 76 soldiers exposed to chronic military stress.
- Participants viewed emotional and neutral visual stimuli during fMRI scans.
- Mediation analyses were performed to link genetic variations, brain activity, and PTSS levels.
Main Results:
- Soldiers with the minor rs17228616 allele showed hyperactivated amygdala responses to emotional stimuli.
- Despite amygdala hyperactivation, these individuals did not exhibit higher PTSS levels.
- Enhanced vmPFC recruitment mediated the relationship between amygdala hyperactivation and reduced PTSS.
Conclusions:
- The miRNA-608/AChE pathway is implicated in threat circuitry and PTSS.
- Individuals with the minor rs17228616 allele may be protected from PTSS due to compensatory vmPFC activity.
- This study suggests a neurobiological mechanism for resilience against trauma-related disorders.
