Interview with Esther Sternberg

Esther Sternberg, MD, is the director of the Integrative Neural Immune Program at the National Institute of Mental Health/National Institutes of Health. She is internationally recognized for her discoveries in central nervous system-immune system interactions and the brain's stress response in susceptibility to arthritis and other diseases, including depression. Sternberg has authored numerous articles, as well as the book, The Balance Within: The Science Connecting Health and Emotions (Freeman/Holt).

Please describe your background and area of expertise.

Sternberg: My area of expertise is the connection between the brain and the immune system. So basically it is how the brain talks to the immune system and how the immune system talks to the brain, and understanding how those connections play an important role in health—in maintaining health and in preventing disease. When those connections are broken, you get disease, and when you maintain those connections, you get health…

The notion that stress could make you sick or that believing could make you well, that the social world had an effect on health—all of that was really hard to prove up until about 15 or 20 years ago, [which is when we finally] had the tools in psychology to define stress loads and mood, and in endocrinology to measure the hormones that are secreted when you’re stressed, and in neurobiology to measure the nerve chemicals that are secreted when you’re stressed, all the way to the immune molecules, cells and genes that make the immune system function.

My expertise is really on the neuroendocrine side. I’m trained as a rheumatologist, and I developed expertise through my research in neuroendocrinology—studying the hormones of the stress response and how they affect immune diseases, like arthritis.

What are some of the interesting things happening in this area today?

Sternberg: The whole field is exploding, and I think it’s amazing—in absolutely every aspect of what I just described; whether at the psychology end or at the molecular biology end, there’s all kinds of exciting advances. Probably if I could pick one, it’s the ability now to link complex phenomena—like psycho-social events, like what’s going on in your psychological and social world—to link them very clearly, to molecular and cellular events at the level, for example, of tumor biology, or at the level of allergic or inflammatory disease.

So it’s the ability to really show what meditation does to the brain and what, in turn, happens when those brain changes occur. What kinds of nerve chemicals and hormones are released that then have an effect on the immune system? What happens when you’re stressed and how [does that] affect the growth of tumors, like ovarian tumors? And not only how [does it] affect the growth but what are the molecules that cause that growth? So those are the kinds of exciting things that are being done today.

Also, putting genetics in there…Of course, with the human genome, we have the ability to identify many genes that are involved in the susceptibility to many different diseases. We know that diseases like arthritis are complex, that there are many genes on many chromosomes that determine whether or not you’re going to get that disease. And we can then link your load of genes that predispose you to develop such diseases with the psycho-social events that you’re exposed to in day-to-day life.

If a person knows that they are genetically susceptible to a specific disease, could he or she use meditation or other complementary therapies to ensure good health?

Sternberg: I think that’s the risk of taking mind-body interventions and discoveries and how beneficial they are too far because you can’t overcome your genes… With multigenic/polygenic diseases, like arthritis, where there are 20 different genes on 15 different chromosomes that predispose to arthritis. If you inherit all 20 of them, you’re going to get the disease. There’s not a whole lot you can do about it… If you inherit two, you’re probably not going to get the disease.

But there’s a dose-effect of genes. If you inherit five or six or 10, then the environmental milieu does play a more important role. If you’re at one extreme or the other of the genetic load, the environment probably has less of an effect. But if you have some load of genes, you can probably delay how long it’s going to take to get the disease, or you may have a milder form of the disease…We don’t know the answers to these questions yet. We do know in rats that if we modify one environmental factor (the maternal behavior), we can, to a certain extent, modulate the adult stress response in [rat] pups.

What we’re learning—and a lot more work needs to be done—is the extent to which these kinds of interventions can help to not overcome, but attenuate, some of the effects of the gene factors, and it really depends on the disease. Nonetheless, all of these kinds of approaches can help improve the quality of life, make you feel better, be less stressed. So to that extent, they can be used as adjuncts to whatever therapy is determined as appropriate—medical or surgical therapy.

Is that kind of genetic testing becoming more accessible to the general public?

Sternberg: I think it is. I think that’s the direction the research and clinical medicine are going. Eventually, we’re going to be able to have 20,000 genes in a microchip measured—we can certainly do it now, but the question is: what does it mean? And once you measure those genes, what do you do about it? Eventually, I think we’ll be able to tailor-make medical treatments for individuals based on their pattern of gene inheritance or mutations or polymorphisms.

Can you give an example of a specific health problem that illustrates how mind and body are connected? What kind of combinations of mind-body therapies and classical treatments could be effective in treating those problems?

Sternberg: I think rheumatoid arthritis is a good example, both because I am a rheumatologist and I have seen a lot of rheumatoid patients, and also because that’s the model that I study in rats. It’s an example that’s been well worked out. For many many years—certainly decades, possibly hundreds of years—it was known by rheumatologists that patients with rheumatoid arthritis had a higher incidence of depression. It used to be…dismissed as “Well, of course a person who has arthritis is going to be depressed because they’re in pain…They may have crippling deformities, and of course they’re depressed.”

However, what the discoveries in our work and others have told us is that the part of the brain (the hypothalamus) that regulates the stress response…is not working right; it’s dysregulated in patients with rheumatoid arthritis. It’s also dysregulated in depression…

It’s not to say that depression is caused by stress. It’s not to say that depression is just stress. It is an endocrine problem. There is a problem in the part of the brain that controls these hormones in depression, and we don’t know if that is primary or secondary. That is, whether you get the depression first and then something happens to the hormones in the stress response or whether there’s a disruption in that part of the brain and the hormones of the stress response that then causes the depression.

But the fact is that it’s there, and in arthritis the same thing happens in the same part of the brain. It suggests that the association between depression and arthritis is not just secondary to having pain. There could be a common underlying hormonal abnormality that predisposes the same individual either to get arthritis, if they happen to come in contact with whatever triggers arthritis…like bits and pieces of bacteria or viruses, or the same individual with the same dysregulation of the hypothalamic stress response center in the brain could develop depression if they encounter a major life stressor or a major life trauma. They could develop one or the other or both because they have an underlying hormonal problem in the same part of the brain that regulates both of these illnesses.

So that’s an example of where understanding the biology can help explain clinical phenomena that we otherwise didn’t understand. Then we can begin to construct appropriate treatment packages.

So if a physician determines that a person with rheumatoid arthritis who's depressed should be on antidepressant treatment, the treatment could actually help to improve the arthritis as well by correcting the imbalance in hormones. An exciting area of psychiatry is now exploring whether the reverse is true—whether anti-arthritis therapy that corrects imbalances in immune molecules can also help to reverse depression. So you can begin to create more appropriate treatment regimens for patients [by] understanding the biology underneath. And certainly doing mind-body interventions can only help if it’s going to attenuate and bring the stress response back into some alignment, some balance … then it could help the anti-arthritis drugs do their job, because you’re not working against the drugs.

Have you seen that with some of your patients in study groups when you treat with anti-depressants that the arthritis begins to improve?

Sternberg: We actually did a study in rats with a drug that was being developed for depression—it’s a CRH antagonist. It’s not on the market—it’s hung up in phase I/phase II trials because they’re trying to develop a form that does not have toxicity. But certainly in the animal models this drug that was developed as an antidepressant reduced the arthritis by 50%. And it’s not because it’s changing the way the rats feel—it’s not that they’re not stressed. It’s that these same hormones (CRH) play a role in arthritis.

So yes, there’s good reason to believe that drugs that are good for depression can also be good for arthritis. It hasn’t been done in large-scale clinical trials…[The hope would be] to find a form of this drug that is not toxic and that perhaps would be beneficial for both…I don’t want to give people false hope, but those are the kinds of things that are on the horizon, that are possible with this kind of research.

How did you become interested in integrative medicine?

Sternberg: It’s been a long road. I started off as a family practitioner—spent two years in family practice and loved it. I noticed one afternoon that half my patients had some kind of arthritis and the other half had some kind of psychological issues, like anxiety or depression. I decided to go back and get more training in rheumatology because I felt like I didn’t know enough about arthritis, and I accidentally fell into a research career because of a patient that I saw, who had developed a scarring, inflammatory skin disease when being given an experimental drug for a very rare form of epilepsy. And to me that was such clear evidence that by doing something to the brain, you could end up with an immune disease, that I just completely changed the course of my career, and I was driven to try to understand how that could happen.

As a rheumatologist/immunologist, I was studying arthritis in two strains of rats that get arthritis, and tested an experimental drug (a serotonin-like drug)… I gave it to the rats, and instead of curing the arthritis in the arthritis-prone rats, it actually killed the control rats that usually never got arthritis, so that was a big surprise. And the only way I could explain that is I knew that the drug had an effect on the brain’s stress response. The only way I could explain this totally unexpected result was that the brain’s stress response had to be important in arthritis in those animals, and that turned out to be correct. So what that did is it really put into focus for me the importance of the brain, and even a specific part of the brain, and even a specific molecule made by that specific part of the brain—how important that is in a particular immune disease, that is, arthritis. We could turn those rats that were otherwise resistant to developing arthritis into rats that were really susceptible to developing arthritis just by changing that part of the brain. And we could correct the arthritis susceptibility in the arthritis-susceptible rats by correcting that part of the brain.

That allowed me then to start thinking in a much broader way about going back to the patients [to consider] endocrine and nervous system and hormonal connections in arthritis and depression.

And then, how did I get even broader into the kind of thing that we’ve been talking about—integrative medicine? I think back about 20 years ago, the task/the challenge for researchers in the field was to prove these connections, to identify these connections, to prove that these phenomena that we’ve known about for thousands of years were real, for example, that stress can make you sick or that believing can make you well. That was the challenge; that was the research challenge.

Now, nobody disputes that there are connections between the brain and the immune system. People laugh, “How could anybody have disputed that?”…Twenty years ago, I was patted on the head and told by the head of my division, “Esther, you’re crazy to do this work. You’re going to ruin your career,” that’s what he said. “You’re going to ruin your career. You can’t do this.” This area of research was considered “fringe.” We got over that hump, and now the big exciting challenge that I would say is not being disputed—it’s being embraced—is to take all of these scientific discoveries and bring them into clinical medicine and really use them to benefit people's health. And then to move to the next frontier, which is maintaining health, rather than just curing disease. So health is a concept in itself, rather than simply the absence of disease. A lot of mind-body interventions are really meant as preventative measures, not as curative measures. That’s where I think the risk is when you talk about using them to treat breast cancer—that should not be done. What you need to do is work with your health professional and your team to integrate these approaches together with the medical and surgical therapies that have been the huge advances in medicine in all of these fields. But at the same time, if you don’t have a disease, develop a regimen to use your combination of mind-body interventions to maintain health.

What is the best thing people can do to improve or maintain their health (whole mind-body-spirit) with regard to your research surrounding the brain-immune interactions?

Sternberg: I think I’ve said it: there isn’t one thing. There isn’t one thing to do for all people, and there isn’t one thing to do for one person at all times in your life. So meditating may be good at one time in your life, and exercise at another. It’s a constantly fluid and changing thing. It needs to be adapted for the particular person in the particular situation, and it could be combinations of things.

A healthy diet is always important. Social support is always important. Some degree of exercise is always important, but…if you can’t do it, if you have some reason why you can’t exercise, a little is better than none. Developing kind of a cafeteria plan of interventions that are comfortable for you to do, that you look forward to doing, not that you have to force yourself to do. The important thing is to work with your health professional to find that balance.

In the self-help world, people often feel if they can’t overcome illnesses, that they’re bad people, that they haven’t succeeded, that they’ve failed, that they’re doing something wrong, and then they feel terribly guilty, and that is absolutely not the message. So first of all, seeking professional help is absolutely essential. You can’t do it on your own. You wouldn’t try to fix your car on your own unless you have experience in being an auto mechanic. So don’t think you can fix yourself on your own. It may take a group of health care professionals with different kinds of expertise to help whatever the problem is. But don’t try to do it on your own. And if these things don’t work, then again, it’s not your fault. It could be that there's just too much of a load in your genes that you can’t overcome it without medical help.

Is there a specific health-related mistake that you see your patients make?

Sternberg: First of all, I should say I don’t see patients anymore…What I tell the public, with whom I do interact a lot, is what I just said: the biggest mistake is thinking you can do it on your own, and then if you can’t succeed, blaming yourself. That is the biggest mistake. So don’t think you can do it all on your own, and don’t blame yourself.

When you say “blaming themselves,” do you mean blaming themselves for getting the disease?

Sternberg: No, for thinking “Well, I’ve meditated, and my breast cancer hasn’t gone away.” That’s not how it works…You need to have a total holistic integrated approach to treating a complex disease, and meditating alone isn’t going to do it. Meditating may help facilitate the drugs having an effect on the surgeries and healing and feeling better. Chronic stress is known to prolong wound healing significantly, so if you’ve had surgery and you do these mind-body interventions that will reduce stress, then you will put your body in a position to heal faster, but it doesn’t mean necessarily that you’re going to be healed tomorrow. I think people have expectations about healing that are based on our “fast food” society. We think, “Okay, I had my surgery, and why is my wound still healing two days later?” Well, you know, the body doesn’t work like a fast food restaurant. The body takes time to heal. Whatever illness you have, it takes time. And what these kinds of mind-body interventions can do is just lay the groundwork to help the body to heal.

Looking to the future, is there anything coming up next on your professional agenda?

Sternberg: I’m writing a book—I’ve just finished the first draft of a manuscript—and it’s coming out in spring of ’09. It’s on healing spaces. How place and space around you helps you heal, like healing environment.