Vol. 2, Special Issue
DR. CASSEM: There is in one really pronounced group. That is depression and intelligence in our artists. There is an over representation of bipolar mood disorder. For instance, all of the romantic poets had major depression. So, Shelley, Keats and Byron all had the mood disorder. You find in Kay Jamison's marvelous recent book individuals who are known to all of us: Churchill, Hemingway. Hemingway shot himself. He had bipolar disorder. For unipolar depression, it's spread. Joe?
DR. COYLE: "Bipolar disorder" is manic-depressive illness. Perhaps creativity is not just related to the depressive episodes, which is profoundly disturbing, but to the manic or hypomanic episodes, where one feels particularly energized and driven and creative. The depression may provide a certain quality to the creativity and the mania may provide the drive.
Q: I'm confused about the correlation between addiction and depression. Does it go both ways? You said addiction leads to depression. Does not depression lead to addiction?
DR. HYMAN: It does go both ways. It is interesting. It appears that, most commonly, drug use comes first. It is especially the case with alcoholism--that is alcohol addiction tends to cause depression. Only in a minority of cases do people drink because they are depressed.
This has practical implications because the first treatment of somebody both depressed and alcoholic is to fully detoxify them. We know also, from genetic studies, that these are even genetically separate disorders.
Q: Do you consider in your research the kinds of chemicals that we are eating, food as a chemical, how we metabolize it, and how it affects our brain chemistry?
DR. COYLE: Actually the chemical transmitter I was talking about, serotonin, is made from an amino acid in our diet called tryptophan. Without getting into the arcane biochemistry, the mechanism for making serotonin is not completely filled with tryptophan. If you eat more tryptophan in your diet, you can make more serotonin in your brain. So, this is an example of a neurotransmitter where its function correlates with the dietary composition. A number of studies show that you can actually enhance serotonin in therapeutic situations to assist certain patients with depression. That's the good news.
The bad news is, you are probably aware, that syndrome that was associated with ingesting tryptophan that was obtainable at diet stores. It was due to a contaminant. So, yes, what you eat does affect your brain function and indirectly may affect such issues as mood.
Q: Have there been similar studies about sugar, the ingestion of sugar?
DR. FISCHBACH: I don't know of any. In fact, with the exception that Dr. Coyle talked about, the brain is very well protected. The homeostatic mechanisms that Steve talked about are very powerful; in fact, most substances don't change brain chemistry beyond the normal limits.
Q: I am a little confused by the connection of stress and depression; a stressed person and a depressed person seem to be different.
DR. COYLE: Let me respond in two ways. Number one is that there is clear evidence from clinical studies that in many episodes of depression, the onset is associated with a very stressful life event. Not all, but many.
Second, if you look at the endocrinologic status of individuals suffering from major depression, over half show an abnormality of the function of their stress hormones. They look like they are incredibly stressed so that there is a defect in the homeostatic regulation of the stress response. Those are the two connections. One is associated abnormality; the other is possibly a precipitant.
Q: One of the most effective treatments in depression is simply to apply a huge electric current across the brain triggering a seizure. How does that work?
DR. COYLE: Because this is certainly a very emotionally laden area, that is, the use of electroconvulsive therapy, let me emphasize that, for people with life-threatening depressions, who either are not eating or driven to kill themselves, electroconvulsive therapy is the most rapid, effective way of treating that depression.
While we don't know completely how it works, it produces changes in the brain that are very much like the changes you see with treatments with antidepressants. We've seen this in experimental animals and in studies in human brain. The difference is that electroconvulsive therapy, or ECT, can produce those changes in a matter of days. The changes in the therapeutic response to treatment with antidepressants takes several weeks. It appears to be working by a very similar final common pathway, although the rapidity is much greater with ECT.
DR. FISCHBACH: I want to emphasize the efficacy of ECT, especially, and the safety of this procedure because it has left such a vivid impression on the public imagination, mostly from movies like "One Flew Over the Cuckoo's Nest." ECT is extremely safe and effective and if you ever had any doubts that there is something wrong with the central nervous system, then the ability of ECT to reverse major agitated depression should convince you otherwise.
Q: On addiction--is the prolonged use of opium derivatives compatible with a reasonable state of health if that person is leading a healthy life otherwise? I'm talking about fifteen years on, say, cocaine.
DR. SHAFFER: Cocaine is not an opiate derivative. But, let's take the original question--is good health compatible with long term ingestion of opiate derivatives? An opiate derivative, for example, might be morphine. In fact, the opiates are relatively non toxic substances taken in a pure form and administered in a non-adulterated way, meaning clean needles or ingested safely. Smoking it presents other problems. All things being equal, the answer to that would have to be, yes. Unfortunately, that set of conditions, as hypothetical as it is, is almost never found.
Q: Can depression trigger disorders in memory, lasting disorders?
DR. ALBERT: We know that severe depression can produce a disorder that sometimes mimics Alzheimer's disease. One of the big problems we have in diagnosing Alzheimer patients is in those who have a depression. Most commonly , what we do is treat the depression and we try to see that we can get it to resolve. Then we look to see whether or not the memory impairment is still remaining, because you can get many of the symptoms of memory impairment, difficulty in concentration, all sorts of things Ned described that can make it difficult for people to use their mental faculties well.
Q: What's happened to using lecithin as a way to replace acetylcholine.
DR. FISCHBACH: There was a treatment designed to increase the levels of acetylcholine in the brain by eating lecithin, especially fish and other sources, which gave rise to a chemical that produced acetylcholine in the brain. What has happened to that idea?
DR. ALBERT: There were numerous tries with lecithin when this finding about decreased acetylcholine in the brain of Alzheimer's patients came about. In fact, you may be interested to know that, at one point it was given in chicken soup. But it was clear that this was really an ineffective treatment. That's why people went to drugs such as tacrine, which were better at maintaining levels of acetylcholine in the brain.
Q: Does prolonged depression change the biochemistry of the brain?
DR. CASSEM: From the perspective of someone who treats depression, the most alarming feature is the way in which it seems to become resistant to medications. I have almost asked the same question as you--does having one more episode actually alter or damage the brain in some way making it more predisposed, more ready to run on its own? With lithium, which has been such a savior for so many people, one finds it becomes ineffective. We find ourselves turning to anticonvulsants used for epilepsy, and they work.
But they lead people like Robert Post to wonder whether or not these episodic insults to the brain did actually induce a change similar to kindling--an experimental technique using single neurons that shows that after a while the neuron had a life of its own, that is, it had epilepsy, so to speak, on its own--and would an episode of depression actually leave a free-running disease in the patient. And it's true, it doesn't seem to take any loss or any outside stress to precipitate another episode. So, that is a concern.
DR. FICSHBACH: I think the blunt answer is yes; there's no question about it. The efficacy of drugs in reversing it, some of the dietary things, and the effects of kindling change both the structure and the biochemistry of the brain.
Q: Is there a relation between cortisol levels and a chemical in the body called endorphin, which acts like morphine?
DR. HYMAN: They actually go up in parallel. The body's own opiates, called endorphins, are released among other circumstances by stress and have certain functions. Cortisol is another hormone released by stress. So, events that cause the release of the body's own opiates also cause the release of cortisol. *