Post-traumatic stress disorder (PTSD) is still sometimes discussed as something that only affects soldiers returning from war. In fact, it is shockingly common even in peacetime – one study found 8 percent of British teenagers have it, frequently undiagnosed. Insight into its molecular basis within the brain is big news on its own, but a molecule that might counteract it would be life-changing. Yet, that is what a new paper is claiming.
Once, soldiers suffering from what was then called shell-shock were told to snap out of it or were slapped by generals. However, as society has come to recognize the massive toll PTSD inflicts on those who suffer from it (and those around them), research has boomed. Treatments from mindfulness to MDMA to listening to brainwaves all show potential.
Nevertheless, scientists are still mostly groping in the dark, unsure of the condition’s underlying basis, so it’s not surprising most treatments only have modest effects or benefit a minority of sufferers. Professor Fang Liu of the University of Toronto may be onto something bigger. She has found that the brains of people diagnosed with PTSD have high levels of a protein complex formed from a glucocorticoid receptor (GR) and FK506 binding protein 51 (FKBP51), exceeding not only levels in the general public but also people with major depressive disorder.
People who have suffered severe trauma but have emerged without the nightmares, hyper-arousal, flashbacks, and insomnia that mark PTSD also have much lower brain and blood levels of the protein complex. The same complex is found in the brains of mice showing fear-instilled responses.
“We believe this protein complex normally increases after severe stress, but in most cases, levels soon go back to baseline,” Liu said in a statement. “However, in those who develop PTSD, the protein complex remains persistently elevated.”
On its own, this discovery would be important, since it would make possible tests for PTSD that could track the progress of treatment and provide evidence to anyone doubting an individual’s condition. However, in the Journal of Clinical Investigation, Liu goes further, announcing a peptide that disrupts the binding between the protein and receptor in mouse brains. Although rodents don’t report their nightmares, apparently mice treated with the peptide experienced molecular changes that restored their brains to more like their counterparts who never had fear responses instilled, and their freeze response changed accordingly.
Liu’s sample size for humans was small, and many medications successful in mice translate poorly to humans. Moreover, since the GR-FKBP51 complex exists in healthy brains, albeit at a lower level, we probably shouldn’t eliminate it entirely. Consequently, the journey to a drug that treats PTSD reliably has barely begun.