Cobbers on the Brain

Anxiety is a common feeling that is a part of every person’s life and can arise due to various situations. However, anxiety disorders include long-term fear and worry with symptoms that can affect every day life. There are many types of anxiety disorders that involve many different symptoms, all of which include persisting worries. The most common anxiety disorders are generalized anxiety disorder, panic disorder, and other phobia-related disorders.

There are many risk factors of an anxiety disorder, including genetic and environmental aspects. Some common risk factors are temperamental traits of shyness in childhood, exposure to stressful and negative life events in early childhood/adulthood, history of anxiety or other mental illnesses, and some physical health conditions.

There are many, varying symptoms of anxiety disorders, but there are some general symptoms across most anxiety disorders. These include panic, fear, sleep problems, difficulty staying calm, sweaty or tingling hands or feet, shortness of breath, heart palpitations, dry mouth, nausea, tense muscles, and dizziness.

Common treatments for anxiety disorders are psychotherapy and medication. Psychotherapy involves talking and discussing a person’s specific anxieties to find the best treatment for what they need. This includes cognitive behavioral therapy, which helps to teach people ways of thinking, behaving, and reacting to stressful situations and objects. Cognitive therapy, which focuses on identifying, challenging, then neutralizing negative thoughts related to anxieties and exposure therapy, which focuses on confronting fears and worries are both examples of cognitive behavioral therapies. Medication does not cure anxiety disorders, but it does help to relieve symptoms of anxiety, panic attacks, fear, worry, and changing moods. Some other therapies for individuals struggling with anxiety disorders may benefit from support groups or stress management techniques. 

When a traumatic event occurs, there is a long-lasting impact on behavior and changes in the brain occur, specifically in the hippocampus and amygdala. The hippocampus regulates emotions and is important in long-term memory. The amygdala is responsible for emotional responses and memory. Both of these brain structures play a role in the response to a stressful situation and the retainment of memories from that experience. The anxiety felt from a stressful situation can inhibit and impair the memories of that experience, causing the formation of strong memories, but negatively affecting the ability to adapt and cope with trauma and stress. There are many parts of the brain affected and conformational changes that are caused by stressors.

The dentate gyrus helps to form new memories and is located in the hippocampus. The main parts of the brain involved in working memory, which is memory that holds 7 items or less at a time and is the ability to remember and process information at the same time, are the prefrontal cortex and the hippocampus. Another main aspect of memory are hormones called glucocorticoids, which includes the main hormone for the stress response and play a role in restoring homeostasis after a stressful situation. Glucocorticoids bind to glucocorticoid receptors (GRs), which are crucial in encoding, processing, and retaining the information of emotional events. The activation of GRs cause a response to stress and long-term changes in the brain leading to the formation of long-term memories of the stressful experience. Moderate stress levels can have a positive effect on memory and brain function, but too much trauma or stress can cause memory loss, cognitive impairments, or increase risk of developing an anxiety disorder.

Overall, stress and anxiety disorders are greatly impacted by areas of the brain can inhibit or stimulate memory when presented with different situations. The difficulty with mental illnesses such as anxiety disorders is all of the possible factors that can be involved and how specific situations can cause changes in the brain that affect the individual for a lifetime. There are still so many unknowns and underlying factors with anxiety disorders, making treatment and future research difficult. Individuals dealing with anxiety disorders all experience them in different ways, which leads to many therapies being geared specifically toward that individual. This can cause deficits to a person’s treatment at first, as finding the right treatment plan for each individual looks different and takes time to discover.

https://www.nimh.nih.gov/health/topics/anxiety-disorders/index.shtml

The Body:

What can’t it do?

It is no mystery that exercise is good for you. Why else would physical education be required in grade school? The extent of the importance of exercise is known oftentime people don’t know the entire picture. Sure, it increases heart health, controls weight, increases muscle mass but it also helps with a myriad of other things including regulating the effects of stress on the body.

Figure 1: There are many ways that exercise can benefit mental health and this figure is just a small snapshot of some of the ways that exercise reduces stress

Source: http://stress-relief-help.com/natural-stress-relief/mindfulness-based-stress-reduction-technique/?stress-relief-help=641903753110408607

A common effect that is seen with stress and several types of mental illness is insomnia. Exercising can increase sleep and sleep quality! Although the way that exercise benefits sleep is still unknown to scientists, researchers at John Hopkins medical school find that exercise increases the amount of slow wave sleep an individual gets. The more slow wave sleep, the more the body has a chance to heal and be ready for the next day.  

There are many effects of exercise on the body and how it increases not only the quality of day to day life but overall life expectancy. The effects on the body are clearly notable, as said above, and have benefits on their own but improving overall self-esteem and outlook are linked to exercise as well. An increase in cognitive functioning is observed as well as relieving tension, which begs the questions — what are you waiting for?

The Brain:

Pump it up!

Exercise increases the amount of the neurotransmitter endorphins in the brain. There are twenty known types of endorphins and are mainly found in the pituitary gland as well as several areas throughout the brain and the nervous system. In this instance, the release of endorphins is called a runner’s high and in addition to this feel good rush of emotions that occurs after exercise, endorphins are also responsible for lowering painful feelings. The receptors that endorphins bind to in the brain are the same ones that are bound to by pain relieving drugs but there is no dependence associated with natural occurring endorphins. The release of endorphins, as said above, is associated with the good vibes that come after exercise and combat not only feelings of stress but are associated with alleviating mental illnesses as well.  

Figure 2:  This hypothetical scan illustrates the areas of the brain before and after moderate amounts of exercise in an individual and the increased amount of endorphins.

Source: http://reset.me/story/this-is-what-happens-to-your-brain-when-you-experience-happiness/

Exercise Queen by GABA: The ABBA cover band of your dreams

Figure 3: These are a few of the ways that you can increase the amount of GABA in the brain which is linked to the reduction of stress.

Source: https://drjockers.com/gaba/

When it comes to stress there is a delicate balance of excitation and inhibition in the brain. The two main neurotransmitters responsible for these phenomenon are glutamate and GABA, respectively. The body responds to stressors in multiple different ways including the activation of the hypothalamic-pituitary-adrenal (HPA) axis. This axis ends in the eventual release of cortisol, a stress hormone, from the adrenal glands atop the kidneys. There are several stress relieving effects that cortisol has on the body including increases the amount of glutamate in the brain. The increase in glutamate also increases the number of free radicals, unattached oxygen molecules, that can do damage to surrounding cells. In addition to this, it is found that there are less amounts of GABA in the brain. Often if you are lacking in GABA you feel overstimulated and on edge all the time. This is because there is not enough inhibition in the brain and too much excitation caused the glutamate. Exercise can also increase the amount of GABA (but really, what can’t exercise do)!

In one mouse study conducted by Princeton University the mice were separated into two groups: one that subjected to exercise and one that were not. There was an increase in both glutamate in both groups but there was also an increase in GABA receptors in the exercise group. The groups were then put into an ice bath, as a method to induce stress, and the amount of firing was measured. It was found in the there was increase glutamate firing for both groups but the group that underwent exercise released GABA and were calmed until retrieved from the water. This demonstrates that the build up of GABA acquired during exercise can be released during stressful situations and diminish the amount of stress felt during these times. This emphasizes the importance of exercise in not only brain health but overall well being.

References:

https://www.mayoclinic.org/healthy-lifestyle/stress-management/in-depth/exercise-and-stress/art-20044469

https://www.webmd.com/depression/guide/exercise-depression#1

http://2018neurochem.pbworks.com/w/page/128067393/Making%20memories%20of%20stressful%20events

https://spinalresearch.com.au/chronic-stress-effects-brain/

https://bebrainfit.com/gaba-supplements-stress-anxiety/

https://medlineplus.gov/benefitsofexercise.html

It’s finals week. You have a to-do list over a mile long and are running on little to no sleep. You have consumed more coffee in the past two days than you have in your entire life. You’re stressed. This kind of stress, although unhealthy, will probably not have a lasting effect on the way you live your life, and soon, your finals week is over.

You decide to drive home to St. Paul, Minnesota for winter break. Suddenly, you hit a patch of black ice on I-94. Your car begins sliding, you lose control, and before you know it you’re hanging upside down in a ditch. Your heart is pounding, your mind is racing, and everything around you is black.

The car accident is now months past you, and you still have no desire to drive again. The memories of that night are forever embedded in your memory. You remember every detail of that night even though you can’t remember what you had for lunch yesterday. Why is that?

The answer may shock you: traumatic life experiences can actually lead to changes in your genes that alter your memory. 

It all starts with the stress response…

When we encounter stress, our bodies release hormones called glucocorticoids. These glucocorticoids do a lot to our bodies under stress, but in the case of altering memory, they are the signals that signal a pathway that will eventually lead to altered gene expression.

So how does this work?

1. You experience a traumatic stressor (car accident, death of a loved one, the list goes on and on…)
2. Your body reacts to the trauma by releasing various molecules related to stress (such as glucocorticoid hormones and glutamate (a neurotransmitter involved in anxiety)).
3. These glucocorticoids travel throughout your entire body, but most importantly, they travel to an area of the brain associated with the formation of long-term memories. This area is known as the dentate gyrus. It is part of the hippocampus and plays a huge role in the formation and storage of new memories. 

   

4. In order for the glucocorticoids to alter memory, they must influence a pathway that plays important roles in the formation of memory. This pathway is known as the NMDA/ERK1/2/MSK1/2-Elk-1 pathway.
5.  In addition to having a long name, this pathway is also responsible for activating the molecules responsible for altering one’s genes.
6. It’s as simple as this:
   1. The activation of the pathway in combination with the glucocorticoids leads to the activation of two different molecules (MSK1 and Elk-1)
   2. These molecules are responsible for putting a “mark” on proteins known as histones, (these proteins are what organize the 6-feet of DNA that you have into your body into your tiny microscopic cells).
   3. This mark is what tells your gene editing machinery to set up shop on your genes and alter how they are read by your body.
   4. After setting up shop, all of the different tools (transcription factors, binding proteins, etc.) will get to work.
   5. Their finished product? Altered genes that are responsible for the reason your car accident is still so fresh in your mind.

Because they are so strongly encoded, these memories can actually be quite harmful as they tend to pop up in everyday life. This is the case for individuals living with PTSD and other stress-related mental disorders. 

There are many individuals that have never experienced a traumatic event, and then there are those for whom trauma is all too familiar.  Although not every traumatic experience will result in changing your way of life, those that do are worth mentioning.

Imagine going through your daily routine without being able to spend more than five minutes without your traumatic experience creeping its way into your thoughts. You begin to fear another traumatic event happening to you and decide to isolate yourselves from the outside world and the people you love. You avoid sleep because you fear that your traumatic event will show itself in your nightmares. You become depressed, anxious, and your sense of self-worth plummets. Your entire life has changed.

This is what life is like for someone with severe PTSD.

Here are a few facts that have been collected from the PTSD Alliance:

• Nearly 70 percent of adults will experience a traumatic event in their lifetime with over 20 percent of those adults developing PTSD.
• Women are twice as likely as men to develop PTSD.
• Individuals with anxiety or individuals who have experienced or witnessed a traumatic event in the past are more likely to develop PTSD.So what can we do about it?
  • Recognize the Symptoms
    • https://adaa.org/understanding-anxiety/posttraumatic-stress-disorder-ptsd/symptoms
  • Help Individuals Get Help:
    • Here are a few helpful tips to help those suffering from PTSD:
      • https://www.nami.org/Learn-More/Mental-Health-Conditions/Posttraumatic-Stress-Disorder/Support
  • Be Understanding: Show Support and Empathy
    • Here is a list of 22 different ways to support someone with PTSD written by people who have it:
      • https://themighty.com/2016/03/22-ways-to-support-someone-with-ptsd-from-people-who-have-it/

Post Traumatic Stress Disorder Fact Sheet

https://moodle.cord.edu/pluginfile.php/708065/mod_resource/content/0/anxiety%20making%20memories%20from%20stressful%20events.pdf

A stressful world

Every day the average person goes through a plethora of stressful events. We go to work, school, or take part in other tasks that demand a lot from our brains. We never have the chance to “get away” from our stressors with the invention of email and smartphones. They continuously remind us of things we have to get done and interrupts our downtime. It seems like many of us, especially college students, have never ending lists of things to do before we get any time to relax. Stress has become such integral component of our daily lives that we are beginning to see more and more cases of anxiety disorders. Research has shown that physical changes occur in our brains as they respond to stress suggesting semi-permanent effects. Our DNA is modified is response to prolonged anxiety causing changes in neural connections. These changes can cause problems with memory and can even lead to heightened anxiety. The topic of stress and anxiety is an important one as it is a common feeling felt in most people and is a prevalent issue in mental health.

What’s going on in our heads?

Anxiety is the brain is a difficult mechanism to piece to together even for top anxiety scientists. Nevertheless, there are some concrete pathways that we for sure know are involved in stress and anxiety. The stress response begins in the brain. The hypothalamus or pituitary gland release hormones into the blood to induce a change in body physiology. Ultimately, these hormones change how we feel and are an integral component of our fight or flight response. However, an imbalance in these signaling hormones can lead to anxiety disorders.

The hippocampus is a structure in the brain utilized in memory consolidation. This structure includes a lot of cells containing receptors for the hormones described previously. It is believed that these hormones are essential for proper memory formation and that too much or too little of them will cause problems with anxiety. In cases of PTSD, it is believed that there are too many of these hormones in the hippocampus leading to a strong association to be made. This results in the formation of a memory that could trigger feelings of anxiety or stress in unnecessary circumstances. The excess hormone in the hippocampus pairs with action of a neurotransmitter called glutamate. Together, these two molecules cause a cascade of signaling to occur resulting in modification of our DNA. This change in DNA causes new genes to be turned on that improve our ability to learn. In many cases this is a good thing, but in cases of PTSD, this means that traumatic events are remembered very vividly and can cause excessive feelings of anxiety. Today, scientists are working to find out how to alleviate the memories of traumatic events while preserving normal functioning in learning and memory.

So what’s the deal? Is anxiety good or bad?

Generally, anxiety is a good mechanism to help keep us safe. If a specific situation causes anxiety, we are generally going to avoid contact with that situation. Perhaps you get anxiety being around snakes so you never touch them or get near them. From an evolutionary prospective, this is very beneficial. Snakes can be dangerous and avoiding them through prevention of an anxious feeling would be beneficial overall. The problem arises when anxiety occurs in situations where it shouldn’t. Social interactions with people you know to be good should not cause a severely heightened sense of anxiety. There is no danger to be anxious about in this situation so there is no reason for us to try to avoid it. Yet many people do get this feeling at seemingly random times. Some people don’t even have to be in a stressful situation to feel stress, they just have to be reminded of one. Perhaps an image vaguely relating to a traumatic event brings on these feelings of anxiety. This is the case for many people with PTSD who experience trauma and are unable to weaken the association of their anxiety to the memory of the event. In these cases, anxiety is a very negative response and holds no survival value. We should remember to avoid dangerous things but these memories should not lurk into safe situations. Further research is necessary to help treat individuals with anxiety disorders because they can have profoundly negative impacts on the person’s quality of life.

The importance of regular exercise for our physical health is drilled into us starting in elementary school gym class. However, there are also mental health benefits that result from exercise. In multiple studies it has been found that exercise has been shown to reduce anxiety levels.

How does this work?

When one experiences a psychological stressor, the pathway in the brain that responds to this is the NDMAR-ERK-MAPK pathway. This process involves multiple steps of phosphorylation and acetylation, eventually resulting in the opening of the chromatin and the alteration of gene transcription. When this pathway is over-activated, it leads to the formation of strong, long-term memories  which are often times associated with anxiety and post-traumatic stress disorder (PTSD).

It is thought that the decreased anxiety levels seen from exercise is due to changes in the GABAergic system. GABA is an inhibitory neurotransmitter; therefore, the increased gene transcription of a GABA synthesizing enzyme allows for more GABA to be created and excreted. With increased levels of this inhibitory neurotransmitter, it is less likely that this anxiety-related pathway will be over-activated leading to decreased levels of anxiety and better response to stress.

These conclusions were determined through experiments with mice and rats, but there was a similar experiment conducted with humans at UC Davis. Participants who exercised showed higher levels of GABA but they were not put through a stress tests like the experiments with mice and rats were. The similar increase in GABA indicates the similar conclusions of the two studies.

Maintaining a Balance

It is crucial that this GABAergic system maintains the correct balance of GABA. As previously discussed, not enough GABA can lead to anxiety and PTSD-related symptoms, because there is not enough inhibitory signaling going on in the brain. On the contrary, too much GABA can be dangerous as well. This excess of inhibitory signals can promote carelessness and cause an individual not to be as aware of danger.

Current Treatments

Medications– used to treat symptoms of anxiety and PTSD but do not target the cause. These are the most commonly used classes of medications.

• SSRIs (Serotonin Reuptake Inhibitors) which are also antidepressants: Fluoxetine, sertraline and paroxetine all work to decrease anxiety, depression and the panic associated with PTSD
• Atypical antipsychotics– risperidone, olanzapine and quetiapine are mostly used to treat PTSD to help with agitation and paranoia
• Mood  stabilizers – sleeping tablets or anti-anxiety medications

Psychotherapy- also referred to as ‘talk therapy’ is very effective for treating PTSD. The patient meets once a week with the therapist for 3-6 months. These therapies include teaching the patient how to reframe their thoughts surrounding the traumatic event and learning how to be in control of one’s feelings

Usually a combination of medication and psychotherapy is used in the treatment of PTSD. However, with the recent research regarding the benefit exercise can have on mental health, that may become part of the treatment plans for this disorder. It would be a more natural way of using the body’s natural functions to try heal the pathways that have been impaired in the brain.

Memories make up who we are as individuals. When memories are interrupted, degraded, or inhibited, we see cases of dementia such as Alzheimer’s Disease–what we discussed last week. There are many different types of memory that people may form (Fig. 1). Explicit memory refers to memories that individuals can consciously discuss whereas implicit memories cannot be distinctly defined or stated. A type of implicit memory is procedural memory. This type of memory exists for skills and actions–like remembering how to ride a bike or play a sport. Procedural memories may also be referred to as “muscle memory” in popular language. Episodic memory is a type of explicit memory that refers to memories regarding autobiographical events–the who, what, when, where, and why. Semantic memories tend to involve facts and concepts.

This week in class, we discussed traumatic memory in regards to PTSD, Anxiety, Depression, and other psychiatric illnesses. Traumatic memory, also called somatic memory, are strong, resilient memories formed following traumatic, psychologically damaging events. In order for an individual to form a traumatic memory, that same individual has to personally experience the trauma. If a societally traumatic event happens around an individual, a memory formed for that event would be considered a flashbulb memory. As defined in 1977 by Brown and Kulik, flashbulb memories refer to emotionally charged memories formed upon learning about a public emotionally charged or traumatic event. These memories are not autobiographical in nature–they did not occur to the person, but around the person. The name, “flashbulb memories,” stems from their nature of allowing the individual to visualize themselves as they were when the event happened, as if they had taken a picture of themselves during that moment.

Although the nature of the memories may differ, flashbulb memories may be similar to trauma or stress induced memories. Originally, Brown and Kulik, 1977, hypothesized that due to their emotional strength, flashbulb memories might be formed using a unique pathway. The researchers also believed that flashbulb memories were not subject to change–that they were stronger than normal memories and not susceptible to the inevitable forgetting and reforming that other memories experience. More recent research has shown the opposite of Brown and Kulik’s claim regarding the resilience of flashbulb memories. A study by Talarico and Rubin, 2003, used a test-retest methodology to find substantial inconsistencies in flashbulb memory recall–from the initial to the latter recall of the memory.

When it comes to traumatic memories, the study of flashbulb memories has helped researchers understand memories that stem from psychological stress. Specifically, one study looked at the memories made by individuals who were not directly impacted, but lived in New York City during the events occurred on September 11th, 2001. The study assumes that the individuals created flashbulb memories of 9/11 and found, using brain imaging, that their amygdalae still showed increased activity levels three years following the events. These individuals were not at Ground Zero, but lived or worked near the epicenter of the attacks. This finding is important for the distinction between flashbulb memories and traumatic memories. Due to their similar nature, it remains unclear if molecular differences exist between the two types of memory.

When discussing these two types of memory, their similarities seem to outweigh their differences. The major difference between the two seems to be whether the individual themselves experienced the traumatic event or if the individual witnessed the traumatic event as an outside observer. Regardless of this characteristic difference between traumatic memories and flashbulb memories, they likely utilize the same formation pathway (Fig 2). Research understands that once formed, both types of memory may lead to the onset of PTSD, Anxiety, Depression, or other psychiatric illnesses if not properly treated soon after the traumatic event. Although different treatment options exist such as pharmaceuticals like SSRIs, atypical antipsychotics, or mood stabilizers, treatment that utilizes psychotherapy tends to be more successful. Common psychotherapy treatment options include Cognitive Processing Therapy (CPT), Prolonged Exposure (PE), and Eye-Movement Desensitization and Reprocessing (EMDR). Each therapy aims to address and process the negative thoughts one possesses due to the traumatic event. Regardless of the treatment process, it remains important to address negative thoughts–as a result of the trauma–as soon as they appear. The earlier the intervention, the less likely an individual is to develop psychiatric illness following a traumatic event.