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New Research Suggests an Unlikely Treatment for PTSD: Antibiotics

There is a new era of PTSD science just around the corner.

 

US Army soldiers carry a wounded comrade injured in an Improvised Explosive Device (IED) blast during a patrol near Baraki Barak base in Logar Province, Afghanistan in 2012. (Photo Munir Uz Zaman/AFP/Getty Images)

With each passing day, the world provides us with grim reminders of a growing public health crisis. Society used to brush it off as a "case of the nerves", before labeling it as "shell shock", but today we know it as post-traumatic stress disorder (PTSD).


As with various other other mental health disorders, after decades of intense study we've greatly expanded our collective understanding of PTSD. We now know that PTSD is a psychiatric condition generated by an individual's exposure to traumatic events, one which manifests itself through a plethora of anxiety-related symptoms.

While our societal and clinical knowledge of PTSD has increased exponentially, our ability to diagnose and treat the disorder hasn't necessarily kept the same pace. Yet a recent study conducted by British and Swiss researchers has yielded an unlikely potential treatment for PTSD, a common antibiotic called doxycycline.

In the study, researchers gave 76 healthy adult subjects either doxycycline or a placebo, then sat them in front of a computer screen that randomly flashed two colors, red and blue. The appearance of one color was associated with a 50% risk of receiving a painful electric shock. After 160 flashes, the study's subjects grew to identify one color with the painful shocks. One week later, the experiment was conducted again with the same subjects, this time without either the doxycycline or placebo. The researchers found that the subjects given doxycycline exhibited a 60% lower fear response than those given the placebo.

Professor Dominik Bach, one of the study's lead researchers, commented: “Learning to fear threats is an important ability … helping us to avoid dangers. (But) over-prediction of threat can cause tremendous suffering and distress in anxiety disorders such as PTSD.” He stated that doxycycline is able to block matrix enzymes, proteins that the brain uses to form memories, which explains why the antibiotic may prove to be an effective treatment in the fight against a disorder caused by an overactive fear memory.

"When we talk about reducing fear memory, we are not talking about deleting the memory of what actually happened," explains Bach. "The participants may not forget that they received a shock when the screen was red, but they 'forget' to be instinctively scared when they next see a red screen."

This is an exceptional forward leap in the theoretical treatment of PTSD. However, this complicated disorder remains firmly gripped by stigma, making its diagnosis particularly problematic.

The U.S. Department of Veterans Affairs estimates that between 7–8% of the adult U.S. population will experience PTSD at some point in their lives, yet there are certain career sectors that possess a demonstrably increased incidence of PTSD among their practitioners. For example, data from the National Center for PTSD suggests that 11–20% of Operation Iraqi Freedom and Operation Enduring Freedom veterans will suffer from PTSD in a given year. Additionally, a recent report issued by the International Association of Fire Fighters states that 20% of firefighters and paramedics have PTSD.

While soldiers and first responders are but two—albeit sizeable—slices of society, they accurately demonstrate the extent to which stigma negatively affects the successful diagnosis of PTSD. Both are not only gritty professions whose members are routinely subjected to repeated psychological trauma, but are industries in which stoicism in the face of carnage has been effectively institutionalized.

In a recent episode of PBS NewsHour, retired Green Beret, Sgt. 1st Class Michael Rodriguez highlighted both the inherent barriers to PTSD diagnosis and the acute need for new diagnostic technologies. He stated, "At that time, I didn’t think I had it. Bought into the stigma. But if there was a tangible test, I think it would make it easier on the patients, but — because it will validate it. You know, like if someone has leukemia, no one ever says, you don’t have leukemia."

It's here that modern science might be able to provide a modicum of relief. Dr. Sam McLean, an emergency medicine physician and anesthesiologist at the University of North Carolina at Chapel Hill, is working to identify PTSD's biological markers through the examination of blood samples in the hopes of developing a lab-based test for diagnosing the disorder. McLean explained the rationale for his research stating, "after a traumatic event, the brain communicates with the body via the blood".

Experts agree that we're likely still years away from ushering these diagnostic methodologies and treatments out of research facilities and into clinics. However, it's incredibly heartening to know that we've not only brought the deadly epidemic of PTSD out of the proverbial shadows, but are aggressively pursuing advances poised to subdue it.  

sebastian-junger-on-ptsd-and-drone-warfare


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Cognitive psychologist Weizhen Xie (Zane) of the NIH's National Institute of Neurological Disorders and Stroke (NINDS) works with people who have intractable epilepsy, a form of the disorder that can't be controlled with medications. During research into the brain activity of patients, he and his colleagues discovered something odd about human memory: It appears that certain basic words are consistently more memorable than other basic words.

The research is published in Nature Human Behaviour.

An odd find

Image source: Tsekhmister/Shutterstock

Xie's team was re-analyzing memory tests of 30 epilepsy patients undertaken by Kareem Zaghloul of NINDS.

"Our goal is to find and eliminate the source of these harmful and debilitating seizures," Zaghloul said. "The monitoring period also provides a rare opportunity to record the neural activity that controls other parts of our lives. With the help of these patient volunteers we have been able to uncover some of the blueprints behind our memories."

Specifically, the participants were shown word pairs, such as "hand" and "apple." To better understand how the brain might remember such pairings, after a brief interval, participants were supplied one of the two words and asked to recall the other. Of the 300 words used in the tests, five of them proved to be five times more likely to be recalled: pig, tank, doll, pond, and door.

The scientists were perplexed that these words were so much more memorable than words like "cat," "street," "stair," "couch," and "cloud."

Intrigued, the researchers looked at a second data source from a word test taken by 2,623 healthy individuals via Amazon's Mechanical Turk and found essentially the same thing.

"We saw that some things — in this case, words — may be inherently easier for our brains to recall than others," Zaghloul said. That the Mechanical Turk results were so similar may "provide the strongest evidence to date that what we discovered about how the brain controls memory in this set of patients may also be true for people outside of the study."

Why understanding memory matters

person holding missing piece from human head puzzle

Image source: Orawan Pattarawimonchai/Shutterstock

"Our memories play a fundamental role in who we are and how our brains work," Xie said. "However, one of the biggest challenges of studying memory is that people often remember the same things in different ways, making it difficult for researchers to compare people's performances on memory tests." He added that the search for some kind of unified theory of memory has been going on for over a century.

If a comprehensive understanding of the way memory works can be developed, the researchers say that "we can predict what people should remember in advance and understand how our brains do this, then we might be able to develop better ways to evaluate someone's overall brain health."

Party chat

Image source: joob_in/Shutterstock

Xie's interest in this was piqued during a conversation with Wilma Bainbridge of University of Chicago at a Christmas party a couple of years ago. Bainbridge was, at the time, wrapping up a study of 1,000 volunteers that suggested certain faces are universally more memorable than others.

Bainbridge recalls, "Our exciting finding is that there are some images of people or places that are inherently memorable for all people, even though we have each seen different things in our lives. And if image memorability is so powerful, this means we can know in advance what people are likely to remember or forget."

spinning 3D model of a brain

Temporal lobes

Image source: Anatomography/Wikimedia

At first, the scientists suspected that the memorable words and faces were simply recalled more frequently and were thus easier to recall. They envisioned them as being akin to "highly trafficked spots connected to smaller spots representing the less memorable words." They developed a modeling program based on word frequencies found in books, new articles, and Wikipedia pages. Unfortunately, the model was unable to predict or duplicate the results they saw in their clinical experiments.

Eventually, the researchers came to suspect that the memorability of certain words was linked to the frequency with which the brain used them as semantic links between other memories, making them often-visited hubs in individuals's memory networks, and therefore places the brain jumped to early and often when retrieving memories. This idea was supported by observed activity in participants' anterior temporal lobe, a language center.

In epilepsy patients, these words were so frequently recalled that subjects often shouted them out even when they were incorrect responses to word-pair inquiries.

Seek, find

Modern search engines no longer simply look for raw words when resolving an inquiry: They also look for semantic — contextual and meaning — connections so that the results they present may better anticipate what it is you're looking for. Xie suggests something similar may be happening in the brain: "You know when you type words into a search engine, and it shows you a list of highly relevant guesses? It feels like the search engine is reading your mind. Well, our results suggest that the brains of the subjects in this study did something similar when they tried to recall a paired word, and we think that this may happen when we remember many of our past experiences."

He also notes that it may one day be possible to leverage individuals' apparently wired-in knowledge of their language as a fixed point against which to assess the health of their memory and brain.

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