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"We think psychiatry is now where the field of oncology was in 1971."


J. Raymond DePaulo Jr., M.D.

Chairman, Department of Psychiatry
and Behavioral Sciences

When Ray DePaulo was named Hopkins' chairman of psychiatry this spring, his appointment also coincided with the publication of his latest book, Understanding Depression: What We Know and What You Can Do About It. Dome talked with him over the summer about both developments.

There are so many books on depression out there, and you yourself have already written one. Why do we need another?

It had been 12 or 13 years since I'd written the first one. I've been waiting until I had enough to say to write another book and also to get right some of the things I didn't get right the first time.

The field has changed in many ways since the first wave of books were published about 15 years ago. There's been a greater public health awareness of depression and bipolar disorder. We have a lot more information, particularly about the cost to and impact on society. We knew depression was widespread, but we didn't know quantitatively what a powerful societal and economic impact it has at work and at home.

When the World Health Organization studied the prevalence of depression, experts found that it ranked between first and fourth in the world as a cause of disability and burden-depending on how they measured severity. Whether it's first or fourth, that means it's very big, and if the impact of suicide had been included in the study, which it wasn't, the estimate of its impact would have increased by 40 percent.

We now have new scientific tools to explain depression in a physiological way. We haven't found the genes that predispose some of us to depression, but there's no doubt about the genetic contribution. Finding the first gene is key. When the first gene for Alzheimer's disease was found, a gene that accounted for less than 1 percent of Alzheimer's, it facilitated the discovery of the next four genes, which account for 40 percent of Alzheimer's disease, and have revealed the basic pathway to the disease.

We think psychiatry is now where the field of oncology was in 1971, when the war on cancer was declared. There's a logic to the work of doctors in oncology now. I have a friend right now with lung cancer. At first, we can try surgery, then chemotherapy, then radiotherapy, and there are immunotherapeutics, too. So we have four distinctly different pathways to go after the cancer, and what's more, we know how each one works.

That's what we need in depression. We can help get most people better, but the problem is we don't know what's making people better. Therefore, we don't know why other people don't get better. That's one of the things I wanted to put in the book-what we know and what we don't know-because I think it helps people make better decisions. My goal was to make patients and families more active participants in their own treatment.

Why is it that so many people have depression? Is it a question of evolution and survival?

It's pure speculation as to why it's such a widespread disease. In one sense, if it was rapidly lethal, it wouldn't be widespread for long. That's why a disease like the plague, for example, comes and goes. If a disease is going to stay widely prevalent, then you probably have to be able to live with it for a while. The fact that Type II diabetes is very prevalent means it doesn't kill people in a hurry. Depression could be compared to that.

But another reason is that these are not single-gene disorders. It takes combinations of genes to get them, even to get the predisposition to them. So if it takes two, three or four genes in some combination to be at very high risk for depression, these genes must be very, very common. I think-again, this is speculation-that the genes by themselves must have some utility and contribute to normal traits that are valuable to us, but that in particular combinations may not be. It's a little like a slot machine in reverse. A single cherry doesn't do you any good, but when you get three of them, it does. In this case, one of the depression genes doesn't do any harm, but when you get three of them, it's a different matter.

Another thing we wonder about with diseases this common is whether new genetic mutations are continuing to appear in the world. It's very possible, but the rates of depression appear to be fairly uniform. Some people think they're going up, but I tend to be skeptical about that. So far, all the societies we've looked at have significant rates of depression.

So there's no happy place?

There's no uniformly happy place. It looks like the rates of clinical depression and bipolar disorders are, if not uniform, then fairly similar across all cultures and geographic boundaries. One reason could be that there are a set of stable gene mutations that have been in the species since before we left Africa.

Are you still working on the genetics of bipolar disorder?

Sure am. Until we get it right. We have not identified any of the genes yet for bipolar disorder. Neither has anybody else. But new tools are coming rapidly. A couple years ago we had the draft sequence of the genome. Now the finished sequence is about 80 percent complete. We'll probably have a listing of all genes within a few years. We won't know all their functions within that time period, but there are many things happening that will make the task of finding genes for bipolar disorder and depression much more doable. It's very hard to find genes when there are four genes involved, say, for one person's disorder.

Once you have the genes, then what?

A gene is a blueprint, a set of instructions for how to make a protein, and the proteins tell a story about what is going right and wrong in the body.

Once we can find several genes for the disorder, for example, we'll be able to use them in the ER when people come in behaviorally disturbed. We'll want to figure out, Is this just the effect of this person taking street drugs? Or do they have something else that makes them tend towards taking drugs all the time. Very hard to tease out. And we probably do at least a million of those evaluations every year in this country. It would be very helpful in the ER or in the clinic where people are seen for the first time and in different states of mind to know quickly what they've got. It turns out that the average patient with bipolar disorder has suffered for 10 years before being diagnosed. If we could cut off those 10 years of untreated illness, that would be enormously helpful.

Once we understand the pathways of the disease through these genes, we'll see how they relate to each other. Then we might find a logical way to interrupt this disease, instead of depending on treatments that work, or fail, for reasons we don't understand.

Do you long for these days?

Can't you tell? There are so many people with these diseases. Understanding bipolar disorder will absolutely pave the way for us to understand depression, an even more prevalent disorder. I get extremely frustrated when even well-intended public media outlets decry a society in which it's easy to take antidepressants. But in fact, we have a situation where people have potentially lethal and very disabling diseases, and they don't get treatment because they don't recognize they're ill. So I would like to educate the media, and the best way for me to do that would be to find the gene.

What is it like being a psychiatrist?

For me, it's an enormous privilege to be able to work with patients. There is nothing more fascinating than the workings of the human mind. You have every opportunity here that medicine can provide. You're working on the most complex functions, accounting for the influences of the brain, the most complex organ, as well as life experience and values and meaning and aspirations. It's all in there. It's an art, but an art informed by science. You begin with patients who feel worthless, hopeless, that no one could possibly understand them. When they come through and say, Oh my gosh, You went with me along this path…. There's just nothing better than that.

When did you decide on psychiatry?

I had an idea about it when I was 17. I was looking at it in a semi-logical way-I laugh when I think of that logic-but my choices were (it was 1963) whether to answer the call of John Kennedy and become a politician, or to use my talent in science and to become a physician to satisfy my curiosity about why people do what they do. Psychiatry offered me the opportunity to do both. I had several family members working on Capitol Hill, conscientious people. My sister wrote gun control bills for 11 years, never to see any of them get out of committee. And I thought, how long can I go without positive reinforcement? Certainly not 11 years; in fact, I wasn't sure I could go a day. So I'm a doctor.

How's the new job going?

Very well. I couldn't be more enthusiastic about the potential we have. There are frustrations naturally with managed care and others who don't seem to understand that we psychiatrists are treating real patients with real diseases. That also makes me very passionate about my research. To be a better clinician, I really need the research, so that we can understand the diseases in a more fundamental way, and teach people that depression is a real disease, as real as pneumonia or stroke. We don't deprive people with heart disease of treatment simply because not all of our treatments are successful. We say, Do your best, for God's sake! Don't quit now. And that's what we need to say to people who are trying to help patients with depression. I do feel that we're gonna get 'em!

-Reported by MEM



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