Cobbers on the Brain

What is anxiety?
Anxiety is a general term for several disorders that cause nervousness, fear, apprehension, and worrying. Anxiety plays a profound role in the impact of psychologically stressful events on physiological, behavioral, and cognitive responses. Stressful events can be anything, such as tests, recitals, or interviews. They are several types of anxiety that we will discuss later.

 
In the brain.

• Stress evokes activation of GABA receptors
• GABA (gamma-Aminobutyric acid) (learn more about Gaba here https://www.everydayhealth.com/gaba/guide/) decrease in the brain (hippocampus, dentate gyrus)
• Decreased GABA Leads to an increase in histone H3 which makes memories stronger.
• We don’t want to make stronger memories of stressful events. Which is what happens in people with anxiety.

What causes anxiety?
As we have seen above, abnormality in the brain can lead to anxiety. Other factors such as the environment, substance use and abuse and medical can also induce anxiety.

1. Environmental factors

• Stress from work, school, financial difficulties, natural disaster, etc
• Trauma from events such as abuse, victimization, or the death of a loved one

2. Medical factors

• Lack of oxygen from emphysema, or pulmonary embolism (a blood clot in the lung)
• Stress from a serious medical illness
• Side effects from medication

3. substance use and abuse

• certain studies have indicated that the increase use of alcohol and drugs play a role in influencing anxiety within users. https://search.proquest.com/openview/b61ecfe6889e591d0e957c25840480e5/1?pq-origsite=gscholar&cbl=40661

Types of anxiety

1. Generalized Anxiety Disorder (GAD)

• chronic disorder
• long-lasting anxiety
• Excessive worry about money, health, work, school.
• have trouble identifying specific fear
• Most common form of anxiety.

2. Panic Disorders

• Characterized by brief or sudden attacks intense terror
• Shortness in breath, dizziness, confusion and other attacks may occur
• Attacks can last for hours
• They can be spontaneous but usually occurs after scary and frightening experiences

3. Social Anxiety Disorder

• fear of being negatively judged by others or a fear of public embarrassment due to impulsive actions
• affects 5% of the general population
• failure to interact with the environment around which leads to avoidance of the environment

Other form of anxiety include, Obsessive-Compulsive Disorder (OCD), Phobias, Post-Traumatic Stress Disorder (PTSD), and Separation Anxiety Disorder.

Treatment for anxiety.
Anxiety can be treated by medication, counseling and self-treatment. Medication is preferred as the last resort for people with anxiety due to its ability to present side effect.

• Learning to reduce stress by being mindful of stressful environment and other self-awareness practices such as, deep breathing, self-talk and exercise have been shown to reduce levels of anxiety.
• Counseling methods like Cognitive-behavioral therapy (CBT) which aims to recognize and change the patient’s thinking patterns that are associated with the anxiety and troublesome feelings, have also be productive in reducing anxiety
• Anxiety medication include Lorazepam (Ativan), Diazepam (Valium), Clonazepam (Klonopin) and Alprazolam (Xanax)

Note: Sometimes alcoholism, depression, or other coexisting conditions have such a strong effect on the individual that treating the anxiety disorder must wait until the coexisting conditions are brought under control.

             Individuals with anxiety already suffer from a debilitating disorder; those with both addiction and anxiety have it much worse.

 
Anxiety is typically caused by extremely stressful events in someone’s life, and while some people learn to cope with the stress, others are never able to fully recover, and suffer from constant stress after the event(s). Stressful situations result with an increase in the level of glucocorticoids, a class of neurotransmitters, in the brain (1). Glucocorticoid hormones can induce the expression of genes associated with memory formation, allowing the brain to form strong memories of the stressful event (1). The formation of these memories can disrupt the balance of activity between different brain regions, and lead to abnormal activity in some regions.
 
One region of the brain impacted by anxiety is the prefrontal cortex. For those of you unfamiliar with the anatomy of the brain, the prefrontal cortex is located towards the front of your head, right above your eye sockets. The prefrontal cortex is responsible for planning, decision-making, emotional regulation, and the development of personality (2).

 
The way the prefrontal cortex regulates emotional responses is by controlling the activity of the limbic system, especially the amygdala. The amygdala is the region of the brain responsible for processing fear and anger, and the fear response becomes activated in extremely stressful situations.
 
Abnormal levels of activity in the amygdala have been associated with anxiety, indicating that the amygdala is partially responsible for the fear and stress felt by those who suffer from anxiety (2). In healthy people, the prefrontal cortex can shut off the fear response in the amygdala when it becomes too activated, but in people with anxiety, the amygdala actually decreases the activity of the prefrontal cortex (2).

This is where anxiety ties into addiction. When the activity of a person’s prefrontal cortex is inhibited, that individual’s ability to process information and make good decisions is significantly reduced. This means people who suffer from both anxiety and drug addictions are not able to avoid behaviors detrimental to their health, such as relapsing on their drug of choice. In fact, drug addicts who suffer from high levels of anxiety were found to be much more likely to relapse (2).
 
The stress caused by anxiety can permanently rewire the brain on the molecular and synaptic levels, making the brain much more susceptible to addiction. For example, the increased levels of glucocorticoids in the brain in anxious individuals can lead to higher levels of dopamine in the limbic system, which in turn makes the reward processing system in the brain more susceptible to drugs (3).

Artstract #2
 
Anxiety and chronic stress are both risk factors for developing an addiction, and given that our culture has extremely high levels of anxiety, we need to be careful about how we learn to cope with the stress we face on a daily basis in order to avoid addiction. We also need to create more resources for those who do suffer from anxiety in our society; otherwise we will continue to see a surge in people addicted to various drugs and unhealthy behaviors.
 
 

Sources:

1.https://moodle.cord.edu/pluginfile.php/625282/mod_
resource/content/0/anxiety%20making%20memories%20from%20stressful%20events.pdf
2. http://www.jneurosci.org/content/29/19/6229
3. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2732004/
 

Image Credits:

1. https://d3atagt0rnqk7k.cloudfront.net/wp-content/uploads/2016/10/13130748/how-does-cbd-work-1024×641.jpg
2. https://insidethealcoholicbrain.files.wordpress.com/2015/08/fofbraindiag.jpg?w=567&h=465&crop=1
3. http://learnmem.cshlp.org/content/16/5/279/F3.large.jpg

Nowadays, more and more people are diagnosed with generalized anxiety disorder (GAD). It seemed like the anxiety is a part of our daily life. I want to discuss some myths about anxiety.
 
 

1. Not all anxiety is bad!

There are healthy anxiety (eustress) and unhealthy anxiety.

• The eustress helps you to focus more in the specific tasks/ projects/ goals. It also motives, encourages for accomplishing as well as preventing you from impulsive actions. Moreover, anxiety helps you to remember not repeating the same mistakes again in the future.
• However, the unhealthy stress causes panic attacks – usually occur in phobia, unhealthy behaviors, and constant worrying. All of these behaviors are come from the disrupt in pre-frontal cortex (PFC), which is responsible for executive functioning and reasoning. This plays a huge role in emotion regulation.

A person with abnormally high levels of stress and anxiety has a high chance of having disrupted PFC region, result in easily making poor decisions.
 
 

2. Anxiety can influence the neuroplasticity

Since anxiety is related to memory formation, the stronger of memory forming makes the person experience more anxiety. This then leads to the unhealthy anxiety.
In the molecular aspect, when H3S10p-K14ac histone is phosphorylated by mSK (mitogen- and stress-activated protein kinase), the histone is decondensed to allow the transcription in c-fos and Egr-1, which are gene induction for memory forming. Before that, mSK is activated by ERK from MAPK pathway and the high level of NMDA (N-methyl-d-aspartat) and glucocorticoid hormone.
 
 

3. GAD is different from post-traumatic stress disorder (PTSD)

People with PTSD mostly experience highly stress when they recall, reflect, and think about the past memories; whereas, people with GAD mostly experience anxiety when they think about the event in the future
 
 

4. Most childhood trauma’s memory is impaired

This is completely different from anxiety affecting on memories, because highly anxiety makes stronger and vivid memories. However, in childhood trauma’s memories are repressed and stored, but they can’t be recovered easily in order to protect the person from the emotional pain.
 
 

5. Non-pharmacological approaches can rewire the neuroplasticity and circuits relating to anxiety!

Cognitive behavior therapy looks at the cognitive component of anxiety and ignores the body manifestation of the disease. During CBT, participants are encouraged to think about their most catastrophic situation, the thing that is causing anxiety and encourage to face with it.
Meditation also has a similar method. During meditation, the participants are sitting comfortably, focusing on your breathing, and then bringing your mind’s attention to the present without drifting into concerns about the past or future. It helps the participants deeply engage in their mind to connect to the inner focus. This practice strengthens the mind’s attention, reducing the thoughts about the future or the past; therefore, the stimulation of these event will be less and may change the neuroplasticity of the brain.
 

Anxiety Disorders

Anxiety has been developing a larger presence in the public eye. This is due to not only ever the increasing numbers of people affected by anxiety, but also to more public awareness programs. Although it is normal to have some stress and anxiety in life, when that anxiety is affecting your daily activities it can become hard to deal with. This is where treatment such as medication, therapy, or exercise can be utilized.

What Is Happening In The Brain

The brain region called the dentate gyrus (DG), the hippocampus, and the amygdala have been implicated in the molecular signaling pathways contributing to high levels of anxiety. Glucocorticoids use glucocorticoid receptors to initiate the ERK-MAPK pathway, resulting in the kinases (enzymes that catalyze phosphorylation) MSK1 and Elk-1 to be activated. Histone H3 is acetylated and phosphorylated by them – this will ‘tag’ the histone – and causes typically silent genes to be transcribed.
In studies using animal models, these molecular signaling mechanisms have proven to play an important role in long-term behavioral modification. GABA also plays an important role in the hippocampus and memory formation. The problem with anxiety disorders such as PTSD is an inappropriately strong negative memory formation to stressful situations.
In summary, an individual’s environment causes a challenge, which causes activation of histone, which leads to epigenetic changes. Because of those changes, we are getting gene expression in the DG that leads to memory formation in the hippocampus. Anxiety makes this worse: treat the anxiety and this can be somewhat lessened.

Negative Memory Bias

In our class discussions, we questioned whether or not people suffering from depression also form the strong negative memories associated with anxiety disorders such as PTSD. In my research, I found that patients with depression typically exhibit a negative memory bias, in which there is an inaccurate recollection of frequency, duration, or specific details of past occasions and occurrences.
Patients have been found to remember more negative than positive words in free-recall tasks, and researchers have also found that it takes significantly longer to retrieve happy memories while in a depressive state than in a happy mood state, and negative memory retrieval time was unaffected by mood state. The negative memory bias typically affects only memories involving the self; this could be due to depressed individuals holding more negative self-schemas.

Exercise and Reducing Anxiety

Exercise is being prescribed more and more by doctors as a way to reduce stress and anxiety. Animal models for researching anxiety have shown that access to voluntary exercise has major benefits on their health, such as better sleep quality, neurogenesis in the DG, and improved cognitive, impulsive, and emotional behavior. Exercise increases the amounts of GABA and decreases amounts of ERK, both of which lead to less of the histone tag discussed earlier. This means you are not making the stress-induced memories causing anxiety.
Society has become more focused on exercise in relation to physical health, but there are many more benefits than just that. The endorphins and neurotransmitters released through exercise are helpful in combating not only depression and stress, but also anxiety too.