Fear is normally a healthy emotion that helps keep us from danger, but for some people it becomes an unmanageable force that consumes their every waking hour. I know because it happened to me when I was fourteen and suffered my first panic attack in Madame Andreassion’s third period French class. It was terrifying because it seemed to come from nowhere. Madame Andreassion was a sweet round-faced woman, and I really enjoyed her class. Why then did I suddenly feel like I was dying of fright? At last the attack finally passed, leaving me shaken but hopeful that the terror would not reoccur. Then the next attack came just two days later, and I began to fear for my sanity.

Today I am doing fine, but it was many months before I felt like my life was under control again. Since then, I have learned a lot about anxiety disorders. In college I made sure to pay special attention whenever the topic came up, searching for any information that would illuminate my own experiences. I discovered that scientists already know an impressive amount about how the brain normally controls fear, and results from their research offer intriguing clues about the frightening disorders that can occur when fear processing goes awry.

It is often difficult to draw the line between normal fear and pathological fear. For example, most people have a natural aversion to heights, and it makes good sense to have a fear of high, open spaces because falling from such a place is likely to result in death. But what if person is so fearful that he cannot travel in an airplane? Depending on his lifestyle, his phobia might only be a minor inconvenience that prevents him from seeing far-off relatives, or it might be a major disruption that limits his success at work. Other people (myself included) are simply high on what we call “trait anxiety”. In layman’s terms, you would probably describe us as “worry-warts”. Sometimes this trait is useful, as our worry gives us foresight into potential problems that others might not see, but other times it hinders us from enjoying what is happening in the present. At what point should a natural-born worrier seek help? Clinicians usually make their diagnoses based on how much the fear is disrupting a person’s life. If Jane has an intense fear of snakes but lives in New York City, chances are that her fear will not require any treatment. Alternatively, if Tom is lonely because his fear of embarrassing himself in front others causes him to decline all social invitations, treating his anxiety would probably help him be happier.

Anxiety disorders have diverse symptoms, from excessive hand washing to inexplicable bursts of panic, to certain fear that one has a terminal illness. Not only do the anxiety disorders include a wide array of features, but the intensity of the disorders can also vary tremendously. Some are relatively mundane worries that are abnormally pervasive, such as whether the oven was left on, but others are seriously debilitating, such as a total inability to leave home. Regardless of the manifestation, all the seemingly bizarre thoughts, behaviors and feelings in these disorders center around feelings of fear and anxiety. Thus it is not surprising that many of the symptoms, such as heart palpitations and hyper-vigilance, overlap across the disorders.

Principle Types of Anxiety Disorders
The most basic anxiety disorder is generalized anxiety disorder (GAD), which is so-named because the person’s fear is not focused on any specific situation or object. Rather, GAD is characterized by intense worry. To get the diagnosis of GAD, a patient must have ongoing symptoms of worry for at least six months, like extreme fatigue, sweating, heart palpitations, hyper-vigilance, and irritability. Studies suggest GAD is one of the most prevalent of the anxiety disorders, affecting about 4% of the population. However, the agreement between physicians on the diagnosis of GAD is low, indicating that the disorder not well defined. The nebulous nature of GAD makes it difficult to conduct research in humans, and it is hard to find a reliable animal model of such high trait anxiety. There is some evidence to suggest that it runs in families, suggesting a genetic component, but most biochemical research has focused on the benzodiazepine receptor complex, since benzodiazepines have been somewhat successful in alleviating GAD. Some researchers have hypothesized that people with GAD have overactive autonomic nervous systems that create a high level of basal arousal, which then causes them to interpret this arousal as a danger signal.

The disorder I had is called panic disorder, and it is characterized by strong somatic symptoms of fear that come on with no warning and seemingly no trigger. To me, it felt like ripples of fear were emanating from my stomach in waves, making my limbs weak and my heart race. The fear built on itself like a spiral until I could not breathe. At times, I was convinced I was having a heart attack. In school, I would have to excuse myself to the bathroom and wait for the panic to pass. The worst part was that I never had any warning they were coming, and once they started, there was nothing I could do to stop the fear from clenching around me like a fist. I found out later that my experiences were very typical for panic disorder. In fact, many people are diagnosed with panic disorder in the middle of an attack, when they rush to the emergency room thinking they are having a heart attack. Treatment for panic disorder is usually a combination of pharmacological intervention with general anxiety-reducing drugs such as tricyclic antidepressants and monoamine oxidase inhibitors, and cognitive therapy that teaches the person not to let the anxiety spiral out of control. Now when I start to feel anxious for no apparent reason, I take several deep breaths and remind myself that I have survived these feelings in the past, and then the fear generally quiets down again.

The Science of Panic
As with GAD, the biological basis of panic disorder is unclear. There is substantial evidence for a genetic component, as identical twins have a higher concordance rate for panic disorder (i.e., both twins have the disorder) than do fraternal twins. Also, people with panic disorder are more likely to have a first degree relative with panic disorder or agoraphobia than people with no anxiety disorder or people with other anxiety disorders. Research on panic disorder suggests that it is likely mediated by the receptors for adrenaline, especially the alpha-2 class of autoreceptors. Autoreceptors normally function as a shut-off mechanism for neurotransmitters, the chemicals that cells use to communicate with one another. When the transmitter is released, it travels both across the synapse and back onto the releasing neuron to attach to the autoreceptors, which then stop further transmitter release. If the autoreceptors are not functioning properly, more transmitter will be released than necessary. In humans, blocking noradrenaline autoreceptors results in increased levels of noradrenaline in the central nervous system (CNS) and can induce panic attacks.

Simple phobia is the most common of the anxiety disorders, and mild fears of specific objects or situations (such as heights or a snake) are common in the general population. However, a significant portion of people (about 7%) have fears that reach clinical significance. Individuals with simple phobias usually have normal basal levels of anxiety and are comfortable when not confronting their feared object. In 1920, John Watson and Rosalie Raynor showed that it was possible to induce a phobia by teaching baby Albert to fear white rats. Since then, most research on the neurological basis of phobia has focused on the brain areas involved in fear conditioning, especially the amgydala. Many phobic individuals do remember a conditioning episode at the beginning of their problem but a significant portion claim the fear seemed to come from nowhere. Treatment is usually systematic desensitization, in which the doctor guides the patient through repeated exposures to feared object until object no longer triggers anxiety.

Possible Origins of Pathological Fear
One of the most popular theories about psychiatric disorders of all types is called the “Diathesis-Stress Model”. This theory proposes that some people are born with a predisposition for a given illness, such as GAD or panic disorder, that may or may not manifest itself depending on the environmental conditions. Supporting this idea is the evidence for a genetic component in all anxiety disorders, coupled with the finding that many people with anxiety disorder report a major life event (the stress) occurring just before onset of their disorder. My history would fit well with this model. Panic disorder runs in my family, so presumably I was born with a genetic risk, and I had a traumatic life event occur before the onset of my symptoms. However, this pattern does not fit all people with anxiety disorders, so it cannot be the only method for developing pathological anxiety.

Researchers have not yet determined what happens to the brain when a person develops an anxiety disorder, but most agree that the disorders represent subtle changes in the normal circuitry underlying fear processing. James McGaugh has devoted most of his career to examining how the brain modulates memory storage, and his results indicate that fear memories are learned faster and retained longer than other types of emotional memory. Indeed, most people’s earliest and strongest memories are of negatively charged emotional events, such as personal injury or death of a close loved one. It is easy to understand why the brain would want to ensure memory of fearful events because they help keep the organism out of danger. However, if the brain areas controlling fear learning are overactive they can cause the organism to generalize the fear to inappropriate stimuli. Two important factors involved in the enhancement of fear memory are activation of the amygdala and the neurotransmitter adrenaline. Direct stimulation of the amgygdala causes animals to display typical fear or aggression reponses, and if the amgydala is removed, an animal no longer shows fear learning. Likewise, overdoses of adrenaline can induce panic attacks, but in small amounts it increases arousal and helps solidify memory. Larry Cahill showed that blocking the body’s adrenaline response by blocking adrenergic receptors in humans selectively reduced their retention of a negative emotional section of a short story. McGaugh and Cahill have both hypothesized that post-traumatic stress disorder, which causes its suffers to re-live an especially traumatic event such as rape or a war battle, may represent an instance where the amygdala/adrenergic system records a fear memory too well. In his research, Joe LeDoux has suggested that simple phobias may be explained by the two main pathways into the amygdala. The higher one is through the cortex and allows for conscious reasoning, while the lower one comes directly from the sensory relay stations of the thalamus. It may be harder to extinguish associations through the unconscious pathway, which might explain why phobias often reoccur outside of the doctor’s office.

A Dark Road but a Bright Future
As it stands now, researchers have a clearer understanding of normal fear processing than the dysfunctions that underlie the anxiety disorders. The deficits seem subtle, which makes them difficult to pin down. Future work with neuroimaging and more specific pharmacological agents should prove informative. The good news for me and others is that complete understanding is not necessary for effective treatment. A combination of drug and cognitive therapy has worked especially well in treating the anxiety disorders, and most people improve dramatically in a short amount of time. However, most of us are never fully cured. We learn to manage our anxiety instead of letting it manage us, but there is always the possibility that the fear could spiral out of control again. Though it has been years since I had a panic attack, there are still times when I feel it lurking close, waiting to throw the blanket over me once more. Well, bring it on, I say. This time I’m ready.

References:
“Generalized Anxiety Disorder, Panic Disorder and the Phobias, ” by Ronald M. Rapee and David H. Barlow, from The Comprehensive Handbook of Pyscholopathology, 2nd Ed., Patricia B. Sutker and Henry E. Adams, eds. New York: Plenum Press, 1993.

Cahill, L, Prins, B., Weber, M, McGaugh, JL, “Beta-adrenergic activation and memory for emotional events.” Nature, 371: 702-704, 1994.

Davis, M. “The role of the amygdala in fear-potentiated startle: implications for animal models of anxiety.” Trends in the Pharmacological Sciences, Vol. 13, 35-41.