Fear

Would You Take a Pill that Wiped Away Fear-Based Memories?

Drugs that target the GR-FKBP51 complex may eventually treat or prevent PTSD.

Posted Jan 14, 2020

People with post-traumatic stress disorder (PTSD) tend to have elevated levels of a biomarker called glucocorticoid receptor–FKBP51 protein complex. Fear-conditioned mice also have higher levels of the GR-FKBP51 protein complex.

A new study of mice with PTSD-like symptoms suggests that using another peptide (TAT-GRpep) to disrupt the GR-FKBP51 protein complex blocks the encoding and recall of fear-based memories and prevents fight, flight, or freeze responses.

This paper, "The Glucocorticoid Receptor–FKBP51 Complex Contributes to Fear Conditioning and Posttraumatic Stress Disorder," by scientists at the Centre for Addiction and Mental Health (CAMH) in Canada was published on January 13 in The Journal of Clinical Investigation.

studiostoks/Shutterstock
Source: studiostoks/Shutterstock

As the authors explain, "Systemic TAT-GRpep delivery reduces freezing. If the GR-FKBP51 complex is part of the mechanism by which fear memories are stored or expressed, disrupting the complex should interfere with these memories. Thus, we tested the hypothesis that our GR-FKBP51–interfering peptide should reduce freezing behaviors in fear-conditioned mice." It worked.

Disrupting the GR-FKBP51 complex in mice seems to block the consolidation of fear-conditioned memories. According to the researchers, this suggests that the same "peptide could treat PTSD symptoms or prevent them entirely."

"The discovery of the Glucocorticoid Receptor-FKBP51 protein complex provides a new understanding of molecular mechanisms underlying PTSD. We believe this protein complex normally increases after severe stress, but in most cases, levels soon go back to baseline levels," senior author Fang Liu said in a news release.

"However, in those who develop PTSD, the protein complex remains persistently elevated, and so this could be a blood-based biomarker for PTSD as well as being a target for pharmacological treatment. In addition, the peptide we developed could be given after a traumatic event, and could possibly prevent the patient from developing PTSD. This is a completely new approach to PTSD and for psychiatric disorders in general."

Clearly, we need better clinical treatments for PTSD. At first glance, a peptide that treats or prevents post-traumatic stress disorder by targeting the FKBP51 protein complex seems like a groundbreaking wonder drug. That said, the ability to give someone a pharmaceutical that blocks the consolidation of fear-based memories could be a double-edged sword with a bright side and a dark side.

It's easy to imagine different ways that administering a drug that wiped away fear-based memories could backfire. Fear-based conditioning is a survival mechanism; we need fear to protect us from hurting ourselves and others. We also need to face our fears head-on and learn to cope with stressful situations to fortify grit and make us more resilient.

Would you take a drug that could prevent fearful memories from sticking or wash away your memory of traumatic events?

The answer to this question will certainly be different for different people. My personal answer is "no." Even though I suffer from mild forms of PTSD and sugar-coat many of the adverse childhood experiences (ACEs) I lived through as a kid and during adolescence, I wouldn't change a thing.

All the negative and positive childhood experiences (PCEs)—along with all "the good, the bad, and the ugly" memories from my past—make me who I am today. 

Without any recollection of traumatic experiences I've lived through over the years, I'd probably have less inner strength and feel incomplete. I'd also probably be less empathetic to others' pain if I couldn't remember what it feels like to hurt.

There's no way I'd want to wash away my traumatic memories; in my mind, they go hand-in-hand with the good memories and the sense of empowerment that goes along with overcoming adversity. (See "New Research Shows When Saying 'I Am What I Am' Matters Most.")

Watching Nikkie Tutorials' heartfelt and triumphant "I'm Coming Out" video on YouTube last night reminded me of the famous 19th-century quote by Thomas Carlyle, "No pressure, no diamonds." Her story also reminded me of how living through traumatic experiences tends to make people more resilient and authentic.  

This morning, Nikkie Tutorials' YouTube "I'm Coming Out" vlog from yesterday (January 13) has 16 million views, two million "I like this" thumbs up, and is #1 on trending.

In this bold video, Nikkie discusses the process of trying to bury or forget about traumatic memories from the past: "You don't want to talk about [the hard times] anymore because you're like, 'okay.' I got through that rough part of my life. I survived. I did it and now I can close it off. But you can never truly close it off for good and I am accepting that nowadays. I am embracing that now because it's time for me to be truly me."

Of course, there are many cases of severe PTSD and trauma where administering "systemic TAT-GRpep delivery" could be a lifesaver. If the latest research in mice from CAMH is correct, some people may be hardwired to be less resilient to traumatic life events than others.

Expecting someone with higher levels of the GR-FKBP51 protein complex to "bounce back" or "reframe" traumatic events as easily as someone without this biomarker could be cavalier.

At this stage, studies on targeting the GR-FKBP51 complex to treat or prevent PTSD are still in their early infancy. Much more research is needed to know if peptides that stop fight, flight, or freeze behaviors in fear-conditioned mice work the same way in humans who have experienced severe trauma.

References

Haiyin Li, Ping Su, Terence K.Y. Lai, Anlong Jiang, Jing Liu, Dongxu Zhai, Charlie T.G. Campbell, Frankie H.F. Lee, WeiDong Yong, Suvercha Pasricha, Shupeng Li, Albert H.C. Wong, Kerry J. Ressler, and Fang Liu. "The Glucocorticoid Receptor–FKBP51 Complex Contributes to Fear Conditioning and Posttraumatic Stress Disorder." The Journal of Clinical Investigation (First published: January 13, 2020) DOI: 10.1172/JCI130363