16.5: Anxiety disorder

Anxiety is something that everyone has experienced at many points in their life. An anxious person may experience cardiovascular symptoms such as elevation of blood pressure and heart rate, shortness of breath, profuse sweating, and a state of panic. In many ways, the anxiety response is similar to the fight-or-flight response observed during sympathetic nervous system activity.

However, a clinical diagnosis of anxiety is different from the passing anxiety that we all experience. Anxiety disorders can be very common, and lifetime prevalence estimates suggest 29% of people could develop clinically significant anxiety over their life span.

According to the DSM-5, anxiety disorders have different presentations.

1. Generalized anxiety disorder (GAD). People with GAD experience a constant sensation of being overwhelmed, accompanied by fear and worry. Many times, this worry is not about a single concern, but rather a combination of issues all at once, such as financial issues, relationship issues, uncertainty of the future, and many others. GAD is much more severe and persists longer than the normal worries that affect everyone.

In GAD, worry persists for several months and is uncontrollable. There are also associated cognitive symptoms, such as fatigue, irritability, difficulty with concentration, and changes in sleep patterns.

2. Specific phobias. With specific phobias, a person develops the anxiety-related symptoms (cardiovascular and psychological changes) in response to highly specific stimuli, such as snakes, enclosed spaces, deep ocean, or public speaking. The person with the phobia perceives the stimulus to be a great threat, even though it does not actually pose a genuine threat. Most people with specific phobias will go to great lengths to avoid exposure to their particular phobia trigger. These phobias are often influenced by social and cultural conditions.

Developing a specific phobia has a lifetime prevalence of about 7%, but only a very small number of people with specific phobias ever seek treatment for their phobia. Like other forms of anxiety, there is a range of severity of these phobias.

Figure 16.17 A person with a specific phobia such as agoraphobia, the fear of unfamiliar environments where they have little control over their circumstance, may experience a panic attack in a crowd.

3. Panic disorder. A person with panic disorder experiences frequent panic attacks, characterized by sudden increases in heart rate, shortness of breath, dizziness, and sudden numbness or tingling (panic attacks can also be seen in specific phobias, but are not observed in GAD.) In panic disorder, these panic attacks may occur independently of external influences.

Pharmacologically, there are a wide variety of drugs that can be used to treat anxiety, broadly called anxiolytics. The first-line therapies are usually SSRIs, the same class of compounds that are used in depression treatment. Other anxiolytics, such as the benzodiazepines alprazolam or clonazepam, act as positive allosteric modulators which increases the effect of the GABA system. Benzodiazepines are not always preferred since they may have misuse potential and can be addictive. Opioids and norepinephrine inhibitors can also decrease anxiety.

The exact cause of anxiety is still unknown. One theory suggests that anxiety is a maladaptive evolutionary response to our modern living conditions. The argument is based on the observation that an anxiety response looks a lot like a mild version of the fight-or-flight, sympathetic nervous system response: both elicit cardiovascular and respiratory changes. For 99% of the evolutionary history of Homo sapiens, we benefited from the sympathetic nervous system as a reflex to improve the odds of survival in dangerous situations. However, our modern civilized living conditions over the past few centuries have been very tame in comparison to the risks that our earlier ancestors experienced. The relative ease of living has let the main function of the sympathetic nervous system fall into disuse. The theory argues that people experience GAD because a part of them encourages sustained activity in the sympathetic nervous system. Although thought-provoking, this theory can’t be tested experimentally and offers no explanation about a biological mechanism that can help to develop a therapy.

Animal behavioral tests for anxiety

As with depression above, there are non-human behavioral tests used to assess anxiety in rodents, such as the elevated plus maze. The maze is a raised platform, with four arms in the shape of a plus sign. Two of the arms have walls surrounding the sides, while the other two are open, exposed on all sides. The rodent is free to move between any of the arms as they choose. Standing in one of the open arms, where they can see the floor far below them, is an anxiety-provoking condition. Under normal circumstances, rodents choose to spend more time in the arms that are surrounded by walls. But if you give these animals an anti-anxiety drug, they increase the time spent in the open arms, indicating a decrease in the behavioral expression of anxiety.

Figure 16.18 An elevated plus maze is one behavioral test for measuring anxiety behaviors in non-human animals.

A related behavioral test is the open field test. The test apparatus consists of a large, flat area where the rodent can move around freely, and some method to track the animal - either an aerial view camera or a series of parallel invisible infrared beams that can locate the animal in the field. In the wild, rodents, as prey animals, prefer to spend more time close to the sides of the testing arena up against the wall, avoiding the wide-open space in the middle where their instinct warns them that they may be snatched up by some predator. However, if you give the rodent an anti-anxiety drug, they will spend more time venturing into the middle of the open field.

Another non-human model of anxiety is the predator exposure paradigm. In this paradigm, an ethologically-relevant stimulus is presented to the rodent, such as one of their naturally occurring predators. In this paradigm, rodent anxiety presents itself as a freezing response, an autonomic nervous system activity spike, and a reduction in non-survival behaviors. Although the predator exposure paradigm has good predictive validity, they may struggle with poor face validity, since the anxiety measures also may appear as many of several other conditions, such as PTSD or stress.