Cortisol: Too Much or Too Little?
As mentioned above, just as overexposure to cortisol is detrimental to health, so is underexposure. Consider the effect of cortisol on the brain. We've known about the links between stress and depression for decades. In the United States alone, stress-related depression accounts for more than thirty billion dollars in medical expenses and lost productivity annually. Researchers at the Institute of Psychiatry at King's College, in London, have determined that stress-related depression actually progresses in two distinct phases. The first phase is characterized by an overexposure to cortisol, creating a "toxic" effect whereby too much cortisol actually destroys crucial brain cells responsible for good mood. The second phase is a compensatory mechanism where the brain becomes resistant to the effects of cortisol as a way to "protect" itself from cortisol's damaging effects. So the brain cells (neurons) are deprived of cortisol, creating a dramatic underexposure that leads to a host of memory and psychological problems. Unfortunately, this syndrome of cortisol resistance leads to a deepening of depression and symptoms of fatigue and confusion, a combination that is very much like the symptoms seen in people with PTSD (posttraumatic stress disorder).
In many ways, you can think of the good/bad aspects of cortisol exposure as you might think of the good/bad aspects of getting too little, enough, or too much exercise. Some is good, but too little or too much are bad. Exercise increases cortisol levels, but this short-term increase in cortisol (similar to the effects of short-term, acute stress) is good for immune function, memory, appetite control, weight loss, sexual health, energy levels, inflammation levels, etc. A total lack of exercise makes you fat and dumb (similar to too much cortisol), and too much exercise is like PTSD (cortisol underexposure) because you get hurt easily and your body cannot respond adequately. Greek researchers have shown us that well-trained athletes have high cortisol during their workouts, but that those levels fall back to normal during rest. Overtrained athletes (who are overstressed), on the other hand, have low levels of cortisol during exercise, but high levels during rest, indicating that their bodies are still under stress, perhaps from injury or infection or inadequate recovery from/adaptation to training. They also experience fatigue, weight gain, depressed mood, and poor physical and mental performance.
Because of the close link between stress and depression, every major pharmaceutical company in the world is attempting to develop new drugs to modulate or balance cortisol exposure. The current antidepressant drugs work primarily on serotonin levels in the brain, and some newer ones also increase norepinephrine levels—but none of them address cortisol exposure. This means that only about one-half of the people who try antidepressant drugs obtain any relief from their depression (yet these drugs still accounted for almost thirteen billion dollars in sales last year). Among the drug companies that are furiously trying to come up with a pharmaceutical answer for stressed-out people with disrupted cortisol balance are Bristol-Myers Squibb, GlaxoSmithKline, Pfizer, Sanofi-Aventis, Johnson and Johnson, Merck, and Novartis. Several of these companies already make an antidepressant drug that increases serotonin levels, including Pfizer (Zoloft), Eli Lilly (Prozac and Cymbalta), Glaxo (Paxil), and Wyeth (Effexor). But because these drugs are only effective about one half of the time, and because they now have to carry a "black box" warning due to their extreme side effects, including an increased risk of suicide, Big Pharma needs a new cash cow—and cortisol control looks like the next target.