Cobbers on the Brain

Anxiety is something we have all experienced on multiple occasions in our lifetime. The first time I remember feeling anxious was when I was three years old. I was onstage in a pink tutu, my hair was in a slicked-back bun, and I had leather ballet shoes on my feet. It was my first dance recital. I included an image to the left so you can picture three-year-old me.

At that time, I was just starting my dance career, and I had never been on the stage before. I remember the lights were shining on me so brightly, and I knew my family (along with dozens of other people) were watching me. I was so nervous to perform in front of all of those people, and I decided that the best way to get out of that situation was to run offstage, tears falling down my face as I did so. My dance teacher at the time (bless his heart) talked to me and calmed me down from my panic before convincing me to go back onto the stage. I followed his advice, and I proceeded to take the stage that night and for fifteen years following that event. The anxiety I felt before going onstage never really went away, but it became a normal part of my life and became more manageable. This is a specific instance, but I have had many experiences with the feelings of anxiety—worry or unease about a specific event or condition.[1] In addition, I have been surrounded by anxiety disorders my entire life (even if I wasn’t aware of what it was at the time).

Anxiety disorders run in my family. I can think of multiple family members that have some sort of anxiety disorder, whether they admit it or not. Generalized anxiety, post-traumatic stress disorder, separation anxiety, and obsessive-compulsive tendencies are all anxiety disorders I have witnessed in my family. Anxiety disorders, however, are different from anxiety. Yes, they tend to share similar physical symptoms, but there are nuances that separate anxiety from anxiety disorders. As I previously stated, anxiety is the feeling of fear or unease concerning a specific event or condition. Physical symptoms of anxiety include elevated heart rate, sweating, having difficulty breathing, and nausea. Though anxiety disorders have these physical symptoms, as well, it is the effect the anxiety has on one’s life that makes it different from anxiety. Anxiety, because it is triggered by an event, has an anticipated end. If you are anxious about an exam you have, the anxiety will likely go away after you finish that exam. Anxiety disorders, on the other hand, are unpredictable—both in duration and triggers. The feeling of uneasiness can last twenty minutes, or it can last for three hours. The triggers can also be unpredictable. A family member I have that has PTSD is triggered anytime she sees rapids in a river, but my anxiety (GAD) is not necessarily triggered by anything. Anxiety disorders are unpredictable, but they are primarily characterized by feelings of anxiety and panic that are out of control, not appropriate for the situation, and interfere with daily activities.[2] More differences are outlined in the picture below.

Many people in today’s society think the term “anxiety” is synonymous with anxiety disorders. The incorrect terminology has been perpetuated through media and has had a generalization effect on anxiety disorders. Many people are guilty of generalizing anxiety disorders (I’m on the proverbial soapbox, but I have also been guilty of doing this), but this generalization makes it hard for anyone with diagnosed with an anxiety disorder to be taken seriously and feel understood. A common response to being startled is “you gave me a panic attack.” This statement invalidates people with panic disorder because now a panic attack is nothing more than a simple fright. Some individuals clean and straighten things up because “my OCD is bothering me.” This statement is invalidating to people with obsessive-compulsive disorder because OCD is now associated only with cleanliness and order—it disregards the two main characteristics of this disorder: obsessive thoughts and overwhelming compulsions.

The main point of this post is not to shame anyone or call anyone out (though I realize now that it seems like it). I just think it is important to spread awareness about the differences between anxiety and anxiety disorders. There are significant differences between anxiety disorders and the feeling of anxiety, and I think not a lot of people are aware of these differences. I think it is important to shed light on the generalization of anxiety disorders and how these generalizations can be hurtful.

[1] https://www.healthline.com/health/anxiety

[2] https://www.mayoclinic.org/diseases-conditions/anxiety/symptoms-causes/syc-20350961

[3] http://invermeresummityouthcentre.org/anxiety/ 

Hippocampus is crucial for memory consolidation, from working memory to long-term memory. The subregions loop through dentate gyrus and CA3 and CA1 areas,.

Cortisol is released by the adrenal glands and is involved in glucose metabolism, blood pressure regulation, inflammatory responses among many others.

Cortisol is necessary when it comes to the fight-or-flight mechanisms, by causing faster breathing, heart rate in case of a stressful event. This is important in small quantity, due to anxiety behaviors caused by elevated cortisol levels in the body. It can potentially be caused by eating disorders, lack of exercise hence making it necessary to practice meditation, exercising, eating nutrient-rich foods.

Along with Cortisol, adrenal glands also secrete glucocorticoid in the hypothalamus, which similarly produces stress response and coping.

The exposure is largely caused by negative events affecting the brain. This could go even beyond into  . There are three major ways that may lead to the occurrence of a trauma/ anxiety behavior. The event,the experience of the event, and the effctts of the event.

Anxiety can be characterized by many different symptoms an individual my experience. From nervousness when talking in front of a large crowed to test taking, these stressful situations can significantly increase and interfere with daily activities. When this occurs, individuals may experience excessive worry, emotional distress, and severe anxiety. Such symptoms are diagnosed as generalized anxiety disorder. In the United States, 40 million adults experience some form of anxiety disorder, most starting before they even turn 21 years old. 

Figure 1.

This number doesn’t specifically refer to the generalized anxiety disorder prevalence, but it does provide an overview of the commonality of anxiety disorders. That being said, there are many types of anxiety that individuals may experience, from generalized anxiety disorder, panic disorder, social anxiety, and specific phobia. Theses are the top leading types of anxiety experienced by people today.

In order to come up with these diagnoses scientists must perform studies an animal models in order to find a baseline for symptoms of anxiety. One way researchers can do this is by conducting a Morris water maze test. Morris water maze test is a conduct strategy generally utilized with rodents. It is generally utilized to conduct spatial learning and memory. It empowers learning, memory, and spatial attempting to concentrate with extraordinary exactness, and can likewise be utilized to survey harm to specific cortical areas of the cerebrum. It is utilized by neuroscientists to quantify the impact of neurocognitive problems on spatial learning and conceivable neural medicines, to test the impact of sores to the mind in territories worried about memory, and to concentrate on how age impacts intellectual capacity and spatial learning. The errand is additionally utilized as an apparatus to consider drug misuse, neural frameworks, synapses, and mental health. 

Figure 2.

There are three phrases used to test the Morris water maze: 

Training phase-    

Escape latency is how much time it takes to find the platform  

Wall hugging can measure the rat not learning or anxiety  

Swim speed can measure how drugs change swim speed and how long it takes to find the platform  

Swim pattern shows the search strategy  

Probe trial-   

Time in target-the removal of the platform can see if the rat is using a strategy to find the general area of the platform when it doesn’t know where it is vs. the rat knowing where it is using a special strategy  

Quadrant-   

Tracks how much time the rat spends on the platform 

The Morris water maze test is one of the most regularly utilized conduct tests to quantify spatial learning in rodents, including rodents and ordinary and hereditarily adjusted mice. It was first evolved and revealed by Richard G. Morris to test the spatial learning conduct of rats. He demonstrated that a hippocampal injury would weaken spatial learning. The test device comprises of a roundabout water tank filled with hazy water and a shrouded stage submerged a couple of centimeters under the water surface in one quadrant of the tank. The tank is encircled by viewable signals. Preparing the creatures to find the concealed stage may take a couple of days (normally 5–7 days). In each preparation preliminary, the test creature is permitted to swim in the water for 5 minutes to locate the shrouded stage. On the off chance that the creature doesn’t discover the stage within the 5-minute time frame, it is safeguarded and set on the stage. Every creature at that point goes through 5 minutes on the stage before being gotten back to its home cage. Every creature has five instructional courses a day. Given that the stage is covered up, the creature must figure out how to utilize the viewable signals encompassing the pool to find the stage. As preparation advances, the time used to locate the shrouded stage will ordinarily diminish. Such diminished break latencies will most regularly mirror the reception of a central inquiry methodology for creatures with no disability in spatial learning. Notwithstanding decreased getaway latencies may likewise mirror the selection of non-spatial methodologies (e.g., mice may figure out how to swim in concentric circles a fixed good way from the divider). In this manner, to separate spatial and non-spatial systems, mice are normally given a test, where the stage is eliminated from the pool, and the mouse is permitted to look for it, commonly over a 60-second time span. Mice having received a spatial procedure will center their pursuit close to the previous area of the stage.

Figure 1: The chemical structure of propranolol.

The use of propranolol

The most commonly prescribed medications typically tend to be those that target immediate health issues such as pain or heart problems. Propranolol is one such medication that is common prescribed for hypertension, coronary artery disease and tachyarrhythmias. However, this medication can readily enter through the blood brain barrier, so there uses can be much more then simply an heart medication.

Figure 2: Diagram of the blood brain barrier.

Mechanism of action

As seen in Figure 2 above, the blood brain barrier can be pretty tricky to cross. So, those medications that can offer a cascade of treatment possibilities. In the case of propranolol, it is a β 1,2-adrenoreceptor antagonist which will compete at the receptor level with catecholamines, thus blocking their effect. This mechanism has also been deployed to block β1,2-adrenoreceptors in the central nervous system. So, it is through the blocking of the catecholamines (adrenaline, noradrenaline, and dopamine) from binding to their corresponding adrenoreceptors that propranolol is able to reduce anxiety.

Figure 3: Commonly used SSRIs used in treatment of anxiety and depression

Why isn’t propranolol prescribed for anxiety?

While the use of propranolol offers many promising results in both animal models and its use in humans, the world of treatment went a different route in the treatment of anxiety. The more recent prevalence of selective serotonin reuptake inhibitors (SSRIs) took the scene before propranolol could be effectively implemented for the treatment of anxiety. SSRIs, as the name implies, act to block the reuptake of serotonin in the synaptic cleft after it has been released. The presence of serotonin in the synaptic cleft has been proven to be an effective treatment for an assortment of disorders, but I’m mainly focusing on anxiety. So, it isn’t so much that propranolol isn’t used because it isn’t effective, but rather because there are more popular substitutes instead.

Figure 4: Generalized pathway for how stimuli is converted into long-term memories.

Function relating to memory

For the article we discussed in class, we mostly looked at how anxiety and stressful situations contribute to memory. This was seen with the use of the forced swim test as the stressful situation led to an increase in memory of the test as well as a corresponding change in behavior (reduced time to begin the immobile phase of the forced swim test). To continue with the idea of anxiety and memory, propranolol actually has an effect on this too!

As seen in Figure 4 above, there is a consolidation step that occurs after short-term memory that helps to convert sensory stimuli into long-term storage. This typically involves protein synthesis. Propranolol acts by selectively inhibiting this protein synthesis of fear inducing stimuli so that the fear memory is unable to be reconsolidated and converted into a long-term memory. It is believed that the selectivity acts by inhibing the feeling of fear in the memory, but leaving the overall memory of the stimulus otherwise unchanged.

The use of propranolol

As discussed above, propranolol is a commonly prescribed heart medication that also has to ability to help treat anxiety disorders, quite effectively. However, because of SSRIs shared ability to cross the blood brain barrier and the increased popularity of SSRIs, propranolol has been reduced to being prescribed for heart problems. But who knows, maybe in those that do have it prescribed, it is doing wonders!

For more information about propranolol, please see the following article here.

Also included is an artstract. I have a couple friends with diagnosed anxiety disorders and when I asked them what it felt like, they said they just get so overwhelmed by nothing and everything at the same time. So , I tried to get that in my drawing.