Potential treatment for PTSD

What could a newly-identified protein complex mean for PTSD?
21 January 2020

Interview with 

Dr Camilla Nord, Cambridge University


PTSD, trauma, mental health


Post-traumatic stress disorder (PTSD) is a common anxiety state triggered by frightening or distressing events. Sufferers speak of becoming hypervigilant for danger, and often develop disabling flashbacks to the events that precipitated their problem. But now scientists in Canada have found a chemical marker that’s present at higher levels in the brain when a person develops PTSD, which might reveal new ways to tackle the condition. Camilla Nord is from Cambridge University’s MRC Cognition and Brain Sciences Unit and has been looking at the new work for us, and she spoke to Katie Haylor...

Camilla - So at the moment there are two main routes to treatment with PTSD. Perhaps the most common is a type of cognitive behavioural therapy, a psychological therapy that really focuses on the trauma, and tries to recontextualize it and reduce those kinds of fear related responses or traumatic flashbacks. And the second is different types of antidepressant drugs, which seem to show some efficacy in treating PTSD.

Katie - And how well do these two approaches work broadly speaking?

Camilla - Neither are perfect. I think the evidence suggests that psychological treatments are a little bit better than antidepressant drugs. But, of course, one of the main symptoms of PTSD is a sort of depression-like state and antidepressant drugs can be quite effective at remedying that, whilst the PTSD-specific psychological therapies can be a little bit better at remedying the flashbacks and the more memory dependent effects.

Katie - So tell us about this study then, what did they seek to achieve?

Camilla - So this study was quite unusual because it proposes a new molecular treatment for post-traumatic stress disorder and it does that by combining mouse research, in which we can look at levels of this new protein complex in mice, with some human results giving it a kind of translational "maybe we could use it in the clinic" type result.

Katie - Okay. Can you just break down what they actually found out?

Camilla - The first was that they found this receptor protein complex. It's got this really wordy name called the glucocorticoid receptor FK binding protein five one complex. So I'll just call it the receptor protein complex. And what they found was that this complex, the levels of it are raised in patients with PTSD but also in a mouse model of PTSD. And then they created their own little protein called a peptide that competes with the FK protein to bind with the glucocorticoid receptors and that essentially makes levels of this whole complex reduce. So maybe a potential treatment for this raised level of the protein complex.

Katie - Do we know practically what it's doing to, say someone's symptoms of PTSD, what's going on in the memory recall or things like that?

Camilla - I think that's totally unclear in human patients because that level of mechanism was only explored in animals. But what did seem to happen in the animal model, which is a kind of conditioning model, so you've got to imagine these mice are essentially exposed to, I think it was a light and a sound, and then they get a foot shock. And once you do that for not very many times, the mice developed this freezing response to the light and the sound. And that freezing response continues even when they don't get the cue. And that's what they call their PTSD symptoms and you could reduce that with this drug. And that gives you a little idea of the sort of avoidance symptoms that could be targeted in humans with this drug.

Chris - That sort of addresses the question I was going to ask you, Camilla, which is how do we know that this complex is bound up with getting the symptoms and it's not just a marker that's nothing to do with causing the symptoms it's just produced as a spinoff of them being there?

Camilla - I still think that both are entirely possible. What you have to remember is that the clinical symptoms of PTSD, as you've already mentioned actually, are things like flashbacks as well as avoidance responses and things like mood. And those more complex areas of symptoms are not modeled at all in a rodent model. So all they have is this kind of freezing avoidance response, so all we know about is the mechanism of that particular avoidance response and how that could maybe be reduced with this new peptide.

Katie - So is this a therapy or is it a diagnostic marker or both?

Camilla - The authors suggest that it's both. What their one human result shows is that in 22 patients with PTSD, levels of this protein complex are different in the same direction as the animals, and they think maybe this could be a diagnostic marker. But what you have to remember is that first of all, it's 22 people and it's not necessarily everyone, at least in their data, that shows that difference. So it's a strong suggestion that it could be a diagnostic marker, but not proof.

Katie - How significant do you think this is?

Camilla - I think it's quite significant for future scientific research. I think I would be a little more tentative about the clinical significance, but certainly what excites me a lot about the results is that I think it opens up a whole new range of studies that we need to do about this protein complex.


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