Exploring Anxiety: A scientific look from humans to preclinical animal studies

Do you remember feeling afraid when presenting yourself in front of an audience? Have you felt nervous when talking to someone because you anticipated possible negative scenarios? Have you had difficulty concentrating thinking about what will happen tomorrow? Have you felt excessive worry about an unknown event? Did you know that these are all common symptoms associated with anxiety?

Anxiety is a psychiatric disorder that is defined as persistent excessive worry and fear about daily situations, impeding a person's daily development. It has been shown that currently the prevalence of anxiety disorder in the world is 4%. In Chile, it has been reported that 1 in 4 Chileans has symptoms of anxiety, which shows us a deterioration in mental health both in our country and in the world. Let us remember that after the Covid-19 pandemic there was an increase in mental illnesses in the world population and it is not difficult to imagine why: many people felt alone, suffocated and there was a great decrease in social interactions, added to the constant stress trying not to get sick, generated a large number of mental disorders in a short period of time, which increased the symptoms and severity of anxiety.

It is important to know that there are various factors that can favor the development of anxiety, among which we find stress that we undergo on a daily basis correlated with, changes in life and the poor ability to adapt to these changes, our social skills, and even genetics itself can predispose us to generate this disorder. That is why we must try to take care of and control the factors that depend on us as much as possible so that these excessive and recurring fears and worries do not prevent us from going about our daily lives.

After reading all these symptoms, did you identify with any of them? If the answer is “yes”, all this leads us to thinking: How can we really know if we suffer from anxiety? This answer is very simple, we must go to a trained professional who can diagnose us and give us appropriate treatment. Currently, there are various treatments available for this disorder, including cognitive-behavioral therapy, medication, and exposure therapy.

If we want to delve deeper into this disorder, we must mention that there are different types of anxiety disorders, which are classified according to the type of trigger, for example we have anxiety disorder generated by an illness, separation anxiety disorder, social anxiety, agoraphobia, which is anxiety about places that can make you feel panic, or generalized anxiety disorder where anxiety occurs due to common events in everyday life, among many others.

At a biological level, there are various structures and molecules in our body that are involved in the development of anxiety. At a structural level, under normal conditions, the “amygdala” is a brain area that is responsible for regulating emotional responses and is active in situations to help us keep our systems alert to stress. The “prefrontal cortex”, an area that is associated with the control of executive functions, is responsible for controlling our working memory, cognitive flexibility and decision making. On the other hand, the “hippocampus” helps us learn and consolidate memory. When we have an anxiety disorder, the connection between these structures begins to fail. Studies have shown a hyperactivation of the amygdala that keeps us constantly alert, as well as an alteration in the communication between the prefrontal cortex and the amygdala, which leads us to making wrong decisions and promotes emotional dysregulation. Finally, at the level of the hippocampus, a decrease in this structure has been found, thus harming memory and emotional regulation.

If we go to a molecular level, there are various neurotransmitters that have been associated with the development of anxiety. For example, a decrease in the neurotransmitter agama aminobutyric acid, known as GABA, has been associated with an increase in anxiety symptoms, since under physiological conditions this neurotransmitter inhibits neuronal excitability and, when decreased, causes continuous activation of the central nervous system. Serotonin, for its part, is a monoamine found in the central nervous system and peripherally. It has been shown that in anxiety conditions there is a significant decrease in the availability of this monoamine. Another neurotransmitter that we can mention is norepinephrine, which is secreted in moments of high stress in order to prepare us for a risk situation. This has been increased in anxiety disorder, causing a hyperalert state in various situations that under normal conditions would not generate anxiety.

But how has everything we know about anxiety currently been researched? Various researchers have dedicated themselves to the study of this disorder using different techniques and models. Within the study models we have, first, humans, where researchers have studied the symptomatology and made the greatest number of approaches without being invasive. But, when it is necessary to make approaches at the molecular level to understand the neurobiology associated with the disorder, and access is required to structures and molecules or to test the effectiveness of drugs in the treatment, animal models are used. One of the most used models are rodents, which have similarities in behavior with humans (face validity), similarities in biological substrates, such as decreased or increased molecules equal to those present in humans (construct validity), and also have similarity in drugs used to treat symptoms (predictive validity). Some of the techniques used to evaluate anxious behaviors in rodents are the open field test and the elevated plus maze. When animals have high levels of anxiety, it can be observed that they spend a high amount of time on the sides of the open field test and a greater amount of time in the closed arms of the plus maze, thus showing anxious-type behaviors.

As we saw during this article, anxiety is not far from the daily routine of our lives, we have all felt some anxiety at some point and the problem finally occurs when that anxiety transforms into a disorder that does not allow us to develop. Everything we know today is thanks to researchers who over the years have studied this disorder through various techniques and study models. If you want to know more about behavioral tests to evaluate anxious or other type behaviors in rodents, keep reading our next posts.

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Belzung C, Lemoine M. Criteria of validity for animal models of psychiatric disorders: focus on anxiety disorders and depression. Biol Mood Anxiety Disord. 2011 Nov 7;1(1):9. doi: 10.1186/2045-5380-1-9. PMID: 22738250; PMCID: PMC3384226.