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News Gram™ March 2005

March 2005 ~ Volume 11, No. 8

Last month, we looked at the specific features of a stress-related syndrome. This month, we can look at what happens inside the body when a person experiences a sudden, overwhelming stressor that is too much for him or her to adjust to in a short period of time. The genesis of the stress response is in the brain. Specifically, neurotransmitters are secreted in various parts of the central nervous system that generates the characteristic alterations in physiological functioning we see in someone whose health or life have been threatened.

The three transmitters are norepinephrine, serotonin and g-aminobutyric acid (GABA). Let's take a brief look at each of them:

• Norepinephrine - This transmitter is found in an area called the locus ceruleus in a portion of the brainstem referred to as the pons. When we recognize that the pons is a very old structure, i.e., one found in organisms that preceded humans in the evolutionary scheme of things, we can see that the anxiety or fear response occurs just as early. The point is that being able to experience anxiety is adaptive; this kind of behavior helps the organism to survive in an uncertain and threatening world. Also, there are a variety of medications that may provoke anxiety attacks by increasing the level of circulating norepinephrine while others reduce the degree of anxiety by decreasing it. The locus ceruleus connects with the cerebral cortex, the limbic system (where emotions are thought to be generated) and the spinal cord.



• Serotonin - These days, serotonin is most commonly identified with the selective serotonin re-uptake inhibitors (SSRIs) that have been found to help reduce anxiety. However, serotonin itself is weakly associated with increased anxiety. It is of some interest that an SSRI such as Prozac may increase the level of anxiety in an individual who takes the medication. People who do take Prozac are usually told to take the medication by noon; otherwise, they might not be able to sleep at night. Serotonin is also found in the brainstem as well as other parts of the brain.



• GABA - This transmitter helps to alleviate anxiety, most commonly when its production and secretion is stimulated by anti-anxiety medications such as alprazolam (Xanax). The use of a drug that antagonizes the functioning of such a medication causes severe panic attacks, thereby implicating GABA in the anxiety response.

What we see in the case of anxiety is that some transmitters increase the level of anxiety and excitation while others have the opposite effect. In this way, the nervous system is able to regulate the functional level optimally. When the balance of these three neurotransmitters is upset, there may be an increased tendency to experience anxiety, either of the sort experienced in panic attacks or in the low level type commonly referred to as anticipatory anxiety. Clearly, the production of anxiety is the result of a neurohumoral imbalance, i.e. an imbalance of secreted materials in the brain and other parts of the body -- induced by specific alterations in the relative levels of these three neurotransmitters.

In brain-imaging studies, the findings are tantalizing but hardly conclusive. Abnormalities in the frontal, occipital and temporal lobes have all been identified in patients with severe anxiety disorders. At some point, the changes in the brain that occur in the presence of a threat will activate a number of alterations throughout the body. For instance, the adrenal gland will be stimulated to secrete cortisol, the "stress hormone" that enables the person to tolerate the acute psychological insult referred to as the stressor. How, though, does the adrenal gland know to increase its secretion of cortisol? The answer lies in the hypothalamus, a structure deep in the substance of the brain associated with regulation of such drives as hunger, thirst, sex and motivation. The hypothalamus stimulates the pituitary gland to secrete adrenocorticotropic hormone or ACTH, which in turn tells the adrenal gland to manufacture and release cortisol.

This mechanism provides a powerful explanation of how emotion-laden events are translated into physiological responses that eventually create a state of the organism we refer to as anxiety. There are a number of different types of anxiety, including panic disorder, post-traumatic stress disorder (PTSD), generalized anxiety disorder, social phobia and obsessive-compulsive disorder. In each of these types, the anxiety episode is something of a surprise. The person does not anticipate it, which is part of what makes it such a threatening experience. While most researchers believe that anxiety is an adaptive physiological and psychological process, it would be very hard to convince the person experiencing it that it is helping him or her to survive.

The panic attack is perhaps the quintessential form of anxiety. It is sudden, short-lived and creates an extreme mental state that makes the individual fear for his continued existence. Circulating hormones cause an increase in the activity of the sympathetic nervous system, which in turn brings about shortness of breath, a rapid heart rate, dizziness, trembling, dilated pupils, increased muscle tension, chest pain and a subjective sense of impending doom.

The pleasing irony in the matter of anxiety disorders is that while such episodes as panic attacks are terrifying, they are also relatively easy to treat. While there may be recalcitrant states of anxiety, a prudent medical regimen of anti-anxiety agents, psychotherapy and old-fashioned reassurance will help most people to return to their previous level of functioning. The anxiety associated with post-traumatic stress disorder is the same anxiety as that found in other kinds of anxiety disorders. The physiology is largely the same as well. As a result, it is now possible to achieve considerable therapeutic success. It is a rare patient who will not be able to return to work after two to three months of treatment. That's a good point to keep in mind!

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