Trauma

Cortisol Signaling Affects Memories of Psychological Trauma

A cortisol-signaling gene (NTRK2) may be linked to higher or lower PTSD risk.

Posted Aug 18, 2020

Gerd Altmann/Pixabay
Source: Gerd Altmann/Pixabay

Memory formation is partly driven by a gene called NTRK2 that regulates cortisol signaling and may influence someone's risk of developing PTSD, according to a new study that examined why some trauma survivors are more likely to experience post-traumatic stress disorder than others. These findings (Vukojevic et al., 2020) were published on August 17 in Proceedings of the National Academy of Sciences.

The University of Basel researchers led by Vanja Vukojevic found that severely traumatized individuals were less likely to experience PTSD symptoms after psychological trauma if their epigenetic profile included more robust regulation of the NTRK2 gene. Of note: NTRK2 was formerly known as TrkB-tyrosine receptor kinase B. (Valent, Danglot, & Bernheim, 1997)

As Vukojevic et al. explain: "[NTRK2] encodes the transmembrane receptor tropomyosin-related kinase B, binds the brain-derived neurotrophic factor (BDNF), and has been shown to play an important role in memory formation." Previous research has shown that BDNF also plays a vital role in neuronal plasticity, neurogenesis, and the efficacy of antidepressants. (See "Beyond Serotonin: Why SSRIs Take About 14 Days to Kick In")

This PTSD study investigated the epigenetic pattern of 12 genes involved in the regulation of glucocorticoid (i.e., cortisol) receptor signaling in two large cohorts of trauma survivors; their goal was to identify specific genes that were involved in memory formation and someone's risk of post-traumatic stress disorder. The cohort for this study consisted of 813 heavily traumatized individuals in Africa; 463 survivors of the rebel war in northern Uganda and 350 survivors of the Rwandan genocide.

The researchers found that traumatized individuals with more robust NTRK2 regulation had fewer traumatic memories and were at lower PTSD risk. Additionally, in a third cohort of 568 non-traumatized individuals, the researchers found that those with stronger NTRK2 regulation got lower scores on a memory performance task. This suggests that NTRK2 activity might facilitate a type of selective amnesia or adaptive forgetting. (Bekinschtein et al., 2018)

This study demonstrates that epigenetic differences in the regulation of NTRK2 are related to memory formation in healthy non-traumatized subjects and may also influence the vividness of traumatic memories, which appears to influence a traumatized individual's PTSD risk.

Based on these NTRK2-related factors, the researchers conclude: "The present findings suggest that epigenetic modifications of NTRK2 are involved in memory modulation in health, and in influencing risk and symptoms of PTSD in case of traumatic experiences."

This study has some clinical implications. Because stronger NTRK2 regulation is associated with weaker memory formation and lower PTSD risk, this could be a new drug target. More specifically, the TrkB receptor (which is inked to NTRK2 methylation) could be a pharmaceutical target. As the authors explain, "TrkB antagonists may be helpful in reducing initial consolidation or reconsolidation of aversive memories. Interestingly, a potent TrkB antagonist was found to have anxiolytic properties in animal studies."

Of course, more research is needed, but these initial findings on the NTRK2-related pathogenesis of PTSD could ultimately lead to new treatments for those exposed to psychological trauma. 

References

Vanja Vukojevic, David Coynel, Navid R. Ghaffari, Virginie Freytag, Thomas Elbert, Iris-Tatjana Kolassa, Sarah Wilker, James L. McGaugh, Andreas Papassotiropoulos, and Dominique J.-F. de Quervain. "NTRK2 Methylation Is Related to Reduced PTSD Risk in Two African Cohorts of Trauma Survivors." PNAS (First published: August 17, 2020) DOI: 10.1073/pnas.2008415117