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PTSD: Cause, Treatment, and New Research

By: Sai Srihaas Potu

Post-traumatic stress disorder (PTSD) is a very common psychological disorder that impacts over 3 million people per year. It is estimated that approximately 8% of people experience PTSD like symptoms throughout their lives. Over the last couple of decades, researchers have been able to develop new psychological therapies in order to treat PTSD. Anyone who experiences some sort of traumatic event during their lifetime is prone to be diagnosed with PTSD.


Many factors can lead to PTSD including trauma, emotional condition, and mental stress. Being able to cope with these factors plays an important role in the successful treatment of PTSD. In recent years, researchers have identified different types of PTSD: dissociative and delayed-onset. Dissociative PTSD refers to the presence of depersonalization or derealization symptoms. On the other hand, delayed-onset PTSD refers to the lack of normal PTSD symptoms until six months after the traumatic event. Though researchers have spent a lot of time working to better understand the mechanisms behind PTSD, there is no effective cure at the moment. However, the treatment options that are available are very effective in addressing symptoms.


Currently, there are several well-known psychological therapies that can help people cope with PTSD. Some of these are:

  • Cognitive-behavioral therapy (CBT) for PTSD focuses on changing how you evaluate and respond to situations, thoughts, and feelings, as well as unhealthy behaviors that stem from your thoughts and feelings.

  • Exposure therapy is a behavioral treatment for PTSD that aims to reduce your fear, anxiety, and avoidance behavior by having you be exposed to thoughts, feelings, or situations that you fear.

  • Acceptance therapy is a behavioral treatment that is based on the idea that our suffering comes from our attempted avoidance of pain. Its overarching goal is to help you be open to and willing to have your inner experiences while focusing attention not on trying to escape or avoid pain, since that is impossible to do, but instead on living a meaningful life.

  • Eye movement desensitization and reprocessing (EMDR) is another effective therapy for treating PTSD that involves thinking about your trauma while paying attention to an outside stimulus, such as a light or a finger moving back and forth. It helps you make new connections between your trauma and more positive thinking.

Subsequently, researchers have been able to develop a new treatment option that helps address the cognitive effects of PTSD. Researchers at the Columbia University Medical Center have discovered that the experimental drug S107 which contains a small compound called rycals can help prevent learning and memory deficits for people with stress-related disorders.


As the years go by, more and more combat veterans are being diagnosed with PTSD. Besides the basic symptoms of PTSD, patients can be prone to other cardiovascular diseases such as heart attack or stroke. Thus, there is a sense of urgency as researchers scramble to create new therapies for PTSD. The study done by the Columbia University researchers provides new insights into the mechanisms that control the onset and symptoms of PTSD.


In recent years, several studies have shown that the structure of neurons in the brain can be dramatically affected by mental stress levels. Researchers have proposed that these effects could be the cause behind many stress-related disorders including PTSD. However, researchers are still not able to identify how cognitive dysfunction arises in patients with PTSD.


Dr. Mark, the lead author of the study, proposed that chronic stress could lead to PTSD through the destabilization of the type 2 ryanodine receptors (RyR2) in the hippocampus, the brain region that plays a central role in learning and memory. RyR2 receptors are channels that regulate the level of calcium in neurons, which is vital to cell survival and function.


In previous studies, Dr. Mark claimed that high-stress levels can lead to the breakdown of RyR2 channels in heart muscle and ultimately the spread of calcium resulting in cardiovascular failure. Subsequently, the failure of RyR1 channels in skeletal muscle can lead to Duchenne muscular dystrophy, limb-girdle muscular dystrophy, and age-related muscle weakness.


In their new study, Dr. Mark used a classic PTSD model in which mice were subject to stressful conditions for three weeks. By raising their corticosteroid levels and activating stress-related genes, the researchers would be able to better understand whether leaky RyR2 channels are a factor in stress-related cognitive disorders.


The researchers found that their previous claim was correct as high-stress levels led to the destabilization of RyR2 channels which led to calcium leaks. With the help of models from heart failure and muscular dystrophy studies, the researchers realized that there was a clear difference between the leaky channels they observed and the ones from normal non-stressed mice which were not leaky.


The results allowed the researchers to conclude that the leaky channels can affect memory and learning, two functions that are impaired in individuals with PTSD. By using classical behavioral and cognitive function tests, they found that the stressed mice developed profound cognitive abnormalities affecting both learning and memory.


The RyR2 channels found in the hippocampus were indeed the main reason behind the cognitive decline in the mice. First, when the mice were given Rycal S107, a novel drug designed in Dr. Marks’ lab that prevents the calcium leak by stabilizing RyR2 channels, cognitive function was not affected by exposure to chronic stress. Second, the researchers created a strain of mice in which stress signals cannot destabilize hippocampal RyR2 channels. When these mice were subjected to chronic stress, they showed no signs of cognitive impairment. Thus, the researchers concluded that Rycal S107 was an effective treatment option for PTSD.


PTSD can occur following a traumatic event. It is characterized by symptoms of re‐experiencing the trauma, avoiding reminders of the traumatic event, negative alterations in thoughts and mood, and symptoms of hyper‐arousal. In this day and age, stress is a very common feeling in everyone’s daily lives. Though there are effective treatment options for PTSD, researchers need to develop an effective and reliable cure that can help the millions of affected people across the world.


References:

1. Andrew R. Marks, Xiaoping Liu, Matthew J. Betzenhauser, Steve Reiken. Role of Leaky Neuronal Ryanodine Receptors in Stress-Induced Cognitive Dysfunction. Cell. 2012.

2. Bisson JI, Ehlers A, Matthews R, Pilling S, Richards D, Turner S. Psychological treatments for chronic post‐traumatic stress disorder: Systematic review and meta‐analysis. British Journal of Psychiatry. 2007.

3. Emmerik AP, Kamphuis JH, Emmelkamp PG. Treating acute stress disorder and posttraumatic stress disorder with cognitive-behavioral therapy. Psychotherapy and Psychosomatics. 2008.

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