Research on disorders of mood and emotions has kept pace with the explosion of knowledge in the past few years about how the brain works, how brain chemicals -- neurotransmitters and neuropeptides -- interact with hormone-producing glands to affect all of the body's functions, from the regulation of the heartbeat to the emotion we call a broken heart, from the blink of an eyelid to an emotional response to something we see.
Scientists at the National Institute of Mental Health have identified a number of chemical abnormalities in some of the complicated feedback systems in people with major depressive or manic-depressive illnesses, and have found a variety of techniques and drugs that can affect emotions and their disorders.
It is still not clear how, or even if, the chemical abnormalities cause the depressions or precisely how some of the useful treatments -- drug and nondrug -- actually work. Most often, a stressful life event will precipitate the first depressive or manic episode, but eventually, especially in bipolar, or manic-depressive, illness, the episodes recur spontaneously.
Nevertheless, progress has reached the point where more than 80 percent of seriously ill patients can be helped.
Dr. Frederick K. Goodwin, scientific director and director of intramural research at NIMH, said recently that "as we are learning more and more about the chemical machinery of the brain, it is becoming increasingly possible to actually design drugs . . . that would be putatively likely to help a particular syndrome, rather than discovering something serendipidously and constructing a theory to match it."
Some new developments in mood-disorder research include:
*Testing of the anticonvulsant drug carbamazepine in manic depressives who are resistant to lithium. According to Dr. Robert Post, an NIMH scientist who has received two professional awards for his work with the drug, some 60 percent of manic-depressives who cannot tolerate lithium appear to do well on carbamazepine (sold as Tegretol). Patients who have many cycles during a year appear to do less well on lithium and better on carbamazepine.
*Worldwide testing of broad-spectrum electric lighting to artificially lengthen the day of persons who are suffering from alternating cycles of winter depression and summer hypomania, a milder form of mania that does not usually require treatment.
Scienitists under the direction of Dr. Thomas Wehr, chief of the clinical psychobiological branch of NIMH, are trying to discover why light works and why by depriving a depressed person of sleep immediately cures the depression -- at least until he or she goes back to sleep.
Some current research involving circadian rhythms, the body's natural cycles, is directed at the thyroid gland. Normally, the pituitary gland produces a hormone in the evening that stimulates the thyroid, but sleep "squashes the process." In patients cycling to mania or in depressed patients deprived of sleep, the levels of the thyroid-stimulating hormone continue to "go up and up and up, flogging the thyroid."
Scientists have found increased levels of thyroid disease in manic-depressive patients, especially those with rapid cycles of highs and lows. This may be another biological link to depression.
*Development of a blood test that appears to detect a difference between manic-depressive patients and those whose episodes are purely depressive. Dr. William Potter, chief of the NIMH section on clinical pharmacology, working with a group of patients already diagnosed as either unipolar (depressive) or bipolar (manic-depressive), has found that simply moving from a lying-down position to a standing position can produce measurable changes in blood levels of norepinephrine -- which Potter calls "noreppy." Norepinephrine is a neurotransmitter, one of the so-called stress chemicals.
Under normal circumstances, this transmitter triggers the release of corticotropin-releasing hormone (CRH). CRH in turn works in the pituitary gland to produce adrenocorticotropic hormone, or ACTH, which triggers the release of cortisol by the adrenals. This body system is linked closely to the cardiovascular system, and indeed, when a normal person goes from resting to standing, the pulse rate increases. In manic-depressive patients, however, the plasma levels of norepinephrine go up, independent of the cardiovascular effects -- pulse or blood pressure. "Noreppy," Potter said, "seems to take on a life of its own."
The test must be done when the patient is in a depressed phase, Potter said, noting that the method for finding norepinephrine is highly complex and not available in most labs. But because the treatments for the two forms of major depressive illness are different, the test "potentially has important therapeutic implications."