MS. DIANE REHMThanks for joining us. I'm Diane Rehm. When we think of mental illness, we don't usually think first of bacteria, parasites or viruses, but a growing body of work suggests that link deserves more attention. In her new book, medical ethicist and author, Harriet Washington, describes the research and stories behind the theory that 10 to 15 percent of mental illness can be linked to infection and what that could mean for our understanding of the brain-body connection.

MS. DIANE REHMHarriet Washington joins me from the studios of NPR in New York. Here in the studio is Dr. Robert Yolken of Johns Hopkins University School of Medicine. And throughout hour, I'll look forward to hearing your comments, questions. Join us on 800-433-8850. Send us your email to drshow@wamu.org. Follow us on Facebook or send us a tweet. And thank you both for being with us.

MS. HARRIET WASHINGTONThank you so much, Diane, for having me on your show.

DR. ROBERT YOLKENAnd thank you for having me as well.

REHMHarriet Washington, the title of your book "Infectious Madness: The Surprising Science Of How We Catch Mental Illness," there has been that connection between germs and mental illness that goes way back. Tell us about that.

WASHINGTONIt does indeed go way back, Diane. Everyone's familiar with rabies. Rabies is transmitted by a virus typically acquired from the bite of an infected animal or a human and we know that it causes the infected person to fly into murderous rages, you know. It has physical symptoms as well, a bevy of them. But people remember it because of the dramatic mental status changes it invokes. And rabies is not alone. There's also pareses, which most people haven't heard of now.

WASHINGTONWe've almost forgotten about it because we've learned. We banished it from our shores. But in the early 1920s, it accounted for one in every 20 hospitalizations in some New York asylums. It's a mental illness that finally was found to be the tertiary stage, the final stage of syphilis infection. So it was cause by a bacterium. So there are a couple very old diseases that we have always known were infectious. I think the trouble is thinking of contemporary diseases that are contemporary problems 'cause they affect many people as being infectious.

WASHINGTONThat’s a different ball of wax, although not totally unprecedented.

REHMSo are you saying that currently doctors are looking at this whole connection in a brand new way?

WASHINGTONOne could say that. There are visionary scientists, like Dr. Yolken, I include him in that number, who, for decades, have been considering the role of microbes not as a replacement for the traditional cause of mental illness that we're all familiar with. Psychosocial causes are still important. Other causes are still important. But there has been a growing appreciation that microbes are also important, a growing willingness to expand the paradigm of mental health illness to include microbial causes.

REHMDr. Yolken, turning to you, how widespread is this thinking within the medical community?

YOLKENWell, I think, as Harriet said, this is an old idea that has been around for a long time and is being resurrected and I think there are a number of reasons for it being resurrected. One of them is that we do have much better techniques now for identifying viruses and parasites not only directly, but also from their footprints, from their effects on the immune system and their effects on the brain.

YOLKENAlso, one thing we have now that we didn't have in the past is the ability to intervene. We have vaccines. We have preventative measures and, of course, we have antibacterial and antiviral agents. So I think this is a good example of an idea where investigators and doctors in the past really set the stage, set the groundwork, but hopefully some aspects of modern science can really help out so that we can totally understand what's going on and eventually do something to prevent and treat these horrible diseases.

REHMHarriet, are we really, though, talking about 10 to 15 percent of mental illness associated with infection?

WASHINGTONIn terms of that particular stat, I'm only the stenographer. That is the guesstimate that I acquired from an area of scientists. I found it compelling that they all gave the same range, 10 to 15 percent, with a very few outliers. So I didn't count them. So that is their guesstimate. And as I explain in the book, it is indeed a guesstimate because no one was able to offer me a rigorous mathematical model for having arrived at it.

WASHINGTONIt was simply the belief of the scientists who are most intimately familiar with this linkage, that 10 to 15 percent is the range that we're talking about.

REHMSo tell me where that data comes from.

WASHINGTONWell, actually, it came from the scientist who I asked. As I said, none of them offered me any rigorous mathematical model to explain why they thought this was the proper range. And if you look at the studies, they're all over the place, which is not surprising 'cause the studies were -- the methodology was very different. Some of them were large. Some of them were small. Some of them used different tools with different sensitivity.

WASHINGTONSo it's not surprising that I saw different percentages in different studies. When I asked scientists what their best estimate or their best figure was, this is what they came up with pretty consistently.

REHMDr. Yolken, apparently one Danish study going back to 2013 looked at medical records of over 3 million people and found some really large percentage of connection. Is that correct?

YOLKENYeah. So let me just say a word about these Danish studies. I think -- I agree with the 10 to 15 percent figure and I think it comes from the fact that a number of individual infectious agents each have an effect that's about two or three fold and we're estimating that they're about 5 or 6 or 7 that might be involved. And it is an estimate because there could be more or could be less. The problem we have is the of timing. That is, that if we have a patient that has schizophrenia or bipolar disorder or severe depression and we measure something in the blood that says this person had an infection, we don't actually know the timing of it.

YOLKENWe don't know if it occurred before or after and that's responsible for some of the large variation that Harriet is speaking about. So what we desperately need is some sort of what an epidemiologist would call a perspective study, that a population where we know something about the exposures and then we can say something about what happens to these individuals afterwards. And, fortunately, in Denmark where they have a system both of universal medical care and also where they can monitor the occurrence of psychiatric disorders and other problems, such as suicide or accidents, they can actually look at the timing. And that's where a lot of these studies are coming from.

REHMYou're a professor of pediatrics. Have you actually seen, in your own studies, in your own practice, indications where infection has lead to, say, OCD, obsessive compulsive disorder, or schizophrenia?

YOLKENYes. The answer is we have. I say that it's rare when we can actually make the direct connection, but we have seen individuals -- in my case, it's usually children who have some sort of acute infection than have a change in behavior and then were able to monitor it back to the infection.

REHMWhat kind of infection?

YOLKENWe've seen infections with herpes viruses and also with the bacteria streptococcus, the group A streptococcus. But I'd like to add, though, that most of the studies that we're doing are actually epidemiological. There are some individual cases, for sure, that doctors deal with, but most of the time we're looking at populations. We're looking at large numbers of people. And the reason for that is that we can monitor infections and we can look at the effect on the population, but it's extremely difficult in any one individual to actually say that that infection lead to that particular behavior.

YOLKENAnd that has to do with a number of factors, some of which is just simply our own lack of knowledge as to what these infections are doing and some has to do with timing of the infection, as I mentioned, or even the genetic make-up of the host. And these are all factors that I think need to be looked at to really understand, to be able to predict which individual will actually have the effect of the infection.

REHMCan you talk briefly about cat scratches?

YOLKENWell, the cat scratch, there is a disease called cat scratch fever, which is a limited neurological disease that one can get from cats. I think, typically, when one is talking about psychiatric disorders, as Harriet did in her book, one is talking about the parasite, toxoplasma. And this is a parasite -- it actually doesn't come from cat scratches, but it's actually excreted in cat feces. So there is a cat association and I think it's fair to say that if we look at all the different infectious agents that have been studied, and there are several, there's not just one, this is the one that's best characterized because we know the most about its life cycle largely from animal studies, but also from human epidemiological studies as well.

REHMAnd what does it look like?

YOLKENIt's a parasite and the primary host is the cat. And by primary host what I mean is that it completes its life cycle in the cat and undergoes sexual reproduction and goes through its entire life cycle. However, unlike other parasites, it has the ability also to infect other animals and from a toxoplasma point of view, the world is pretty much divided between cats, where it can go through its complete life cycle, and non cats, which would be essentially any other warm-blooded animal, humans mice and so on. And that gives it another chance to get out in the community and then re-infect people.

REHMDr. Robert Yolken, he's with the Johns Hopkins University School of Medicine. Short break here. We'll be right back.

REHMAnd welcome back. We're talking about the connection, real or otherwise, between infection and mental illness. I have in my hands a new book by Harriet Washington. She's also the author of the National Book Critic Circle Award book titled, "Medial Apartheid." Her newest book is titled, "Infectious Madness: The Surprising Science of How We 'Catch' Mental Illness." She's on the line with us from an NPR studio in New York. Here in the studio is Dr. Robert Yolken, director of the Stanley Laboratory of Developmental Neurovirology. He's professor of pediatrics at the John Hopkins University School of Medicine.

REHMAnd now joining us is Dr. James Giordano, scholar in residence and chief of the Neuroethics Studies Program at Georgetown University Medical School. Thank you for joining us, Dr. Giordano. I wonder what your thinking is about the connection between some kinds of infectious disorders and mental illness.

DR. JAMES GIORDANOWell, you know, Diane, it's a good question. There's been a fairly long history, certainly over the past 10 to 15 years, that's demonstrated at least a tentative link or correlative link between certain forms of psychopathology and the prior to existing presence of infectious diseases. We see this with things, certainly like Lyme disease, Mycoplasma, toxoplasmosis, a host of viruses, including things like Cytomegalovirus, herpes, and also bacteria such as strep and certain forms of staph.

DR. JAMES GIORDANOWhat we know is that this may either be a direct process -- we now recognize the brain being somewhat more vulnerable as a immunological target and organ -- or it may be an indirect process, where these infectious disorders, these infectious conditions then prompt a body-wide level of inflammation that certainly then also, quote, "spreads to the brain." We know that there are certain cells in the brain called glial cells that are immunologically competent and active cells.

DR. JAMES GIORDANOAnd in some individuals who have genetic or physical vulnerabilities or dispositions -- infectious diseases in childhood or adolescence or even in adulthood -- may then trigger a brain-like response that changes the activity in brain networks that are involved in a host of different aspects of thought, emotions and behaviors, that then manifest psychopathological, where we see symptoms of mental illness.

REHMAll right. I'd like to read to you all an email from Tory. He says, over 10 years, my sister was hospitalized and treated with a million drugs for bipolar disorder. She was finally tested for Lyme disease, which she had at very high levels. After being treated over a couple of years, she's gone from being an emotional mess who could barely take care of herself, to a married, happy mom, with a solid job. Many Western doctors, including my sister's very expensive psychiatrist, who prescribed drug after drug after drug, do not believe in the connection between mental illness and infection. Harriet Washington, did you see, looking back at the research, a connection between Lyme disease and the development of mental illness?

WASHINGTONI didn't actually address Lyme disease in the book, although it has been amply addressed elsewhere with a great deal of both clinical and anecdotal evidence, that indeed there are mental health sequelae, and I think that there are. I didn't address it because I, frankly, could not address everything that fascinated me. And I knew it had been, you know, dealt with copiously elsewhere.

REHMNow, what about you, Dr. Giordano? Have you seen any such connection?

GIORDANOOh, yes. I mean, we know that. The problem with Lyme disease, it's not only the actual causative agent, which is tick-borne -- it's called borrelia burgdorferi -- but in some individuals, they'll then develop a secondary immunological reaction that has been definitely indicated to suggest a whole process of abnormal responses in the brain: changes in the vasculature of the brain, changes in the functional aspect of nerve cells and glial cells, and also the release of certain chemicals in the brain that then will produce either a localized or a more global inflammatory state. And that inflammatory state in the brain can lead to a variety of signs and symptoms that present as mental illness.

GIORDANOAnd we realize that in some cases these are fairly defined. We see things like obsessive-compulsive symptoms, high levels of anxiety, lethargy, melancholia that fall into the depressive categories. So I think the tentative link between bodily conditions that are infectious and brain states that give rise to mental signs and symptoms is becoming somewhat more clear...

REHMHmm.

GIORDANO...but also requires further investigation.

REHMAll right. And of course, first, you have to identify the Lyme disease, which in and of itself is so difficult. But Dr. Yolken, could you take us through an example of what this really looks like in a patient -- a child, for example, who is infected with strep and then begins to show examples of symptoms of obsessive-compulsive disorder?

YOLKENYes. The process that James described is exactly what happens. A child is exposed to a particular type of strep, group A streptococcus, the kind that causes strep throat, commonly caused. And we know actually that there are a number of procedures and diseases that happen afterwards. And these have been very well described. They actually go back to the 18th century. And these are all related to the immune response to the streptococcus. Again, they're usually not related to the bacteria themselves but to the immune response.

YOLKENAnd when the immune response affects the brain, there are a number of conditions that can occur. The classic one is called chorea or Sydenham's chorea where children have unusual body movements, St. Vitus' Dance is the name that was a very descriptive name that was given to it. And we have seen cases -- I've seen cases and other pediatric infectious disease doctors have certainly seen cases where obsessive-compulsive disorders and other neurological and psychiatric problems happen after a strep throat. The problem that we have -- and I think this is really a critical issue -- is that we need better tests to understand -- strep throat is very common.

YOLKENWe don't want to scare anyone, because many parents have children with strep throat and it can be appropriately treated. And we don't actually have good ways of predicting which children will go on to get problems and which ones won't. And that's really a challenge. And I think we have to know more about the bacteria and we have to know more about the host, the genetics of both. And that's really a challenge.

YOLKENAnd it's true for Lyme disease as well. The same thing would really apply. Lyme disease is fairly common, especially in Maryland where we are. But the comments that Lyme would lead to psychological or neurological diseases are relatively rare. But they do occur and we need to understand more about who is actually going to suffer these problems.

REHMAnd, Harriet, you've seen that link between strep throat and OCD. It's been widely debated. Give us the background on what's been called PANDAS.

WASHINGTONWell, PANDAS is an acronym for an unpronounceable -- at least to us laypeople -- syndrome that links group A streptococci, or GAS infections for short, with the development of these disorders in children, in adolescence typically. And the theory is that repeated exposure to these particular streptococci do challenge the nervous system, harm it in such a way that the symptoms of OCD, Tourette's, anorexia, a bevy of childhood disorders can be evoked by it. But as Dr. Yolken pointed out, this happens in a minority of children. Very few of the children who suffer from strep throat are going to go on to suffer the symptom.

WASHINGTONDr. Susan Swedo at the National Institute of Mental Health has been studying this for at least 16 years that I know of and probably longer than that. And she has acquired a large pool of patients and has actually tried to treat them with antibiotics. The studies have been going on for quite a while and it's really important because, you know, it's human study which I think, as Dr. Yolken suggested, is not terribly plentiful sometimes in this field. So there is a -- one thing that she has pointed out is that exposure to the microbes is very individual. Other things can affect it.

WASHINGTONSo trying to determine who is going to be vulnerable for developing PANDAS means trying to determine what possible, for example, genetic or preexisting immunological -- what characteristics a child might have that might make them more vulnerable to this...

REHMI see.

WASHINGTON...so that we can avoid panic and sort of focus on the children who are likely to be at risk for this.

REHMAnd, Dr. Giordano, where does the controversy emerge about PANDAS?

GIORDANOWell, you know, I think that both of our speakers have brought up an interesting point in terms of who's going to be most vulnerable or are there actually identifiable predispositions? Dr. Yolken's point is very interesting because much of the accumulated evidence would suggest that in the developing brain -- for example, in the child or the adolescent -- there's a particular brain area that is referred to as the basal ganglia that may be particularly susceptible to these PANDA-like effects. And as that then develops or react to immunological stressors, you see abnormalities, particularly in its function and perhaps even in its structure that can then lead to these signs and symptoms that we then classify as OCD, Tourette's.

GIORDANOAnd they all have a common denominator, is that they deal with impulse control and repetitive behaviors and abnormal movements. So the issue then becomes, can we pre-identify individuals who would be susceptible to this and should we treat them? And/or should we also be able to parse out or select out those individuals who may be most vulnerable and in some way treat them differently. Of course, this thing gets into the idea of what level of assessment and intervention should be widely available to children? And this gets us into the much larger question of what techniques and technologies are currently accessible, how much we should use them, are we overusing these -- such things neuroimaging, immunological tests, et cetera?

GIORDANOAnd of course, that is somewhat ethically as well as economically controversial.

REHMAnd, Dr. Yolken, to you, are children more vulnerable than adults to the possibility of these bacterial infections resulting in mental illness?

YOLKENChildren are clearly more susceptible. And babies are probably more susceptible than older infants because the brain is developing. I'd like to say though that some adult diseases that we have -- that we deal with, such as schizophrenia and bipolar disorder, often have their roots in childhood. So, yes, the child brain is more susceptible. But sometimes we see this in what we think of as adult diseases -- adult-onset diseases. And that has to do with the development of the brain that occurs between childhood and adulthood, largely in adolescence.

REHMAll right. I'm going to open the phones. Let's go first to Rick in Manassas, Va., you're on the air.

RICKHi. This has an interesting history that goes back farther than people might realize. In 1991, a friend of mine -- his name is Ron Smith -- published two articles on this topic. One was on the macrophage theory of depression and another was on the t-cell theory of schizophrenia. Now the link between mind and body that we're looking at as a result of these chemicals called cytokines-- and it's important for people to know that they're affected by practically everything we do: by diet, by exercise, by lack of sleep and by psychological stress. And these chemicals can be manipulated for our benefit by living a healthier and better lifestyle. And in addition, antidepressants affect these medications as well.

REHMAll right. Thanks for your call. Dr. Giordano, do you want to comment?

GIORDANOWell, I think that Rick makes a wonderful point. I mean, there's certainly strong advocacy for trying to live a fairly stress-free and healthy lifestyle. The macrophage theory, postulative depression, I think is interesting because it really did suggest -- and rather strongly -- a body-brain, if not body-mind link. And the issue there is we've gained a much greater understanding since the early 1990s of the role of a whole host of pro-inflammatory chemicals that may act particularly on the developing brain, but also upon susceptible adult brains, where now you have an adult predisposition or vulnerability that various forms of physiological or even psychological environmental stressors may then exacerbate.

GIORDANOSo I think Rick raises a wonderful point. I think he also raises a good point for further research.

REHMAnd you're listening to "The Diane Rehm Show." Let's go now to Beth in Chevy Chase, Md. You're on the air.

BETHHi, Diane. Thank you so much for taking my call.

REHMSure.

BETHI'm thrilled to hear this being discussed. Briefly, we're a family who's been very touched by PANDAS with our oldest child, who suffered from it for about four or five years. We have been able to keep it in somewhat of a remission with antibiotics and periodic steroid use to help treat infectious triggers as well as keep the swelling in her system down.

REHMTell me how he developed PANDAS.

BETHShe was...

REHMOh, she.

BETH...a classic case of absolute overnight onset. She had a strep infection. And about three or four days later -- which was treated with antibiotics -- about three or four days later, over the course of about two hours, she had a complete personality change. She went from a normal, happy eight-year-old child to a child who was cowering in the corner, who looked like she was in fight-or-flight mode. She had terrible rages and anxiety. And overnight -- absolute overnight, or even hourly, over a couple of hours, onset of severe obsessive-compulsive disorder. So, you know, we -- this was in, around 2008, and we did not know what in the world had happened.

BETHAnd we went down the psychiatry route, because everyone said, a child does not have an overnight psychiatric break without severe trauma. So we went through some terrible months of trying to figure out what had happened before we finally found our wonderful doctor, Dr. Beth Latimer, who has been a pioneer in the field of PANDAS research. And we figured out what it was. We figured out that she had chronic strep hiding in her throat as well as that I was a carrier of the strep gene -- of the strep bacteria, without being actually infected.

REHMWow.

BETHAnd so I had my tonsils removed and she was treated with a lot of antibiotics over several months. And we were able to bring her largely back to her normal self. Now, with that said, over the next four years, an infection or illness would send her right back down into this spiral of OCD, compulsion, rage. And it is absolutely horrific to live through. The other PANDAS families out there know exactly what I'm talking about, trying to survive with your child with, you know, you suddenly -- your normal child absolutely disappears and you have this child who doesn't sleep, who rages, who is, you know, terrified. When it progresses, they can become anorexic very quickly because the obsessions and problems with anxiety can cover food...

REHMAll right. And, Beth, I'm sorry, we've got to stop you right there. I am so sorry for what your child and your family has gone through. We'll take it up after we come back.

REHMWelcome back. And my guest, Dr. Robert Yolken of Johns Hopkins University School of Medicine. He is in the department of pediatrics. Harriet Washington is the author of a new book titled "Infectious Madness: The Surprising Science of How We 'Catch' Mental Illness." And Dr. James Giordano. He's in the Neuroethics Studies department at Georgetown University Medical Center. You have all heard Beth in Chevy Chase, Md. outline the symptoms her daughter experienced within 24 to 48 hours after having been diagnosed with strep. Now, Dr. Yolken, how common is this kind of turn of events and personality change and behavior?

YOLKENWell, fortunately it's rare, but unfortunately when it does occur, just as Beth was describing, it can be devastating. And we don't, as we've talked before, don't totally understand why this happens to some children. As she was describing, most of the children that this happens to are perfectly normal, well cared for, and everything is fine before that. So there's something unusual about the strep or perhaps about the person's -- the child's immune response at that particular time. And I think her story in the episodes outline a couple things that are important.

YOLKENOne is that we in the infectious disease and immunology field have to work with child psychiatrists and adult psychiatrists as well, so at least they will consider this possibility when there is an acute change. Because the story that she describes I think is a common one where this wasn't picked up until later. Secondly, I think there is some hope in this area. Most of what we're seeing in PANDAS or these kind of situations probably is what Dr. Giordano is describing, which is that it's the activation of the immune system.

YOLKENAnd I think the pharmaceutical industry is interested now in working on what the previous speaker spoke about, which is sidakines (sp?) and coming up with very specific ways of interfering with sidakines in ways that don't interfere with the rest of the immune system.

REHMOkay. But I was fascinated that Beth spoke about the fact that she had strep, undemonstrative strep, and that apparently that kept bouncing back to her daughter. Harriet, can you comment?

WASHINGTONWell, the first thing I wanted to just point out is that the very rapid onset, very sudden onset, and the regression. You know, many parents say their children seem suddenly to act like a much younger child, are characteristics of children who do indeed turn out to have PANDAS. Could you repeat your question, please?

REHMThat she, herself, Beth, had untreated strep within her own throat.

WASHINGTONIt puts me in mind of a point that was made repeatedly to me as I spoke to many scientists working in this area, that sometimes when people are seen by physicians, and clinically they can't find any reservoir of infection or evidence of infection, sometimes what's needed is a screen that is more sensitive, that there is a difference in the sensitivity of screens, and that can sometimes make the difference between making an association and not making it.

REHMBut you, Dr. Yolken, have said that in some cases the entire family has to be treated.

YOLKENYes, and the more general cases, the one that Harriet makes in her book very well, which is a bacteria can be very tricky. They have ways of infecting that make it difficult to often find them. And one of the ways that group A strep does is it will, as Beth was saying, hide out in adults that are perfectly asymptomatic. And the best approach, which I think many pediatricians will do, is that if there is a recurrent strep infection, to try to, in fact, find the parents, siblings, other people that are close to the child and get cultures on them as well, or treat them. Sometimes it's even hard to detect in cultures because our tests don't always have the sensitivity that we want, as Harriet was saying.

REHMDr. Giordano, do you believe that sufficient numbers of physicians understand these risks?

GIORDANOThat's a difficult question. I certainly do believe, and I think there's evidence to demonstrate, that the viability of PANDAS and other inflammatory, immunological related body to neurological disorders is increasing, so that the more evidence that is available, the more this becomes a known factor among a variety of different physicians, certainly pediatricians, neurologists and psychiatrists. I think the larger question that you ask here, Diane, is how that's actually going to affect the practice of psychiatry.

REHMTrue.

GIORDANOAnd whether or not this may then lead also to what sometimes would perhaps be considered a heightened medical model of psychiatry, that then engages more directly with other areas of medicine. And I'm optimistic, because I think one of the things this also helps to demonstrate is that psychiatric disorders very often do have a very strong biological basis, and can, in fact, be treated via biological nexus. I think the question then is to really determine who his most susceptible to these things...

REHMYeah.

GIORDANO...why they are susceptible, and then what that means for new avenues of psychiatric intervention, including various forms of pharmacology, as Dr. Yolken identified.

REHMAnd, Harriet, talk about the latest research linking infection and schizophrenia.

WASHINGTONThe latest research that I know of actually touches upon Dr. Yolken's work. The Toxoplasma gondii, it's really interesting. One of things I wanted to know, and I asked both Dr. Tori (sp?) and Dr. Yolken, was when do we think children might acquire this. Is it likely they actually acquire it in the womb? You know, so if the mother has influenza or the mother harbors Toxoplasma, can the child acquire it that way? And the answer was that can happen, but it was thought that it's more likely children acquire it when they're young children. And I thought, why? You know, why is that?

WASHINGTONOne of the most recent papers by Dr. Yolken points out that, for example, they found that, you know, sandboxes that young children play in tend to be a reservoir for Toxoplasma gondii. They're used as litterboxes by, you know, a large number of cats every year. And so unwittingly we're allowing our children to play in these sandboxes where they're, you know, exposed to this. And I found that fascinating. Certainly not the only area of exposure, of course, but one I think that everyone can relate to and understand.

WASHINGTONAnd also interesting to me because it points out -- like a lot of this research points out avenues for prevention, which in my opinion is in some ways even better than treatment. You know, if you administer treatment, often some damage is already done. There's a limit what you can do. But in terms of prevention, one can, you know, completely avoid, evade, you know, the exposure to these pathogens and the damage they do. So that's the hopeful portion of this for me.

REHMAnd, Dr. Yolken, talk about that research you've done into the risk of schizophrenia beginning with the fetus.

YOLKENWell, we think Toxoplasma very clearly can affect the fetus. And that's been well known. But if it affects the fetus very early, one has the manifestations of what we'd say congenital Toxoplasmosis, which is an overwhelming disease often associated with severe mental retardation and visual problems or blindness.

REHMOkay. But how does that adult get Toxoplasmosis?

YOLKENSo we know that that's probably not the case in most cases of schizophrenia, and that's why we think the exposure is later, either the very end of pregnancy, because we do have some studies in pregnant women, or also early in childhood. Now, how one gets Toxoplasma, it's -- as I was saying a little bit before, it's a very complicated parasite, and a very smart parasite, so it's found several ways to get back into people. One way -- and of course it's not trying to get back into people, it's trying to get back into a cat, but in doing so it'll affect any animal. One way is directly from cat feces. And children will get exposed probably from sand because it's aerosolized, and also from soil. And that's been well shown.

YOLKENIn other countries, in other places in the world it can get into the water supply. So one cat can defecate in water and actually contaminate very large numbers of people. And, in fact, if we look at Toxoplasma as an international issue, there's much more Toxoplasma -- there's a lot of Toxoplasma in the United States, but there's much more in areas of the world that have problems with water purification. Many places in Latin America and Africa and Asia, and that is related also to cats as well.

YOLKENFarm animals and feed animals like cows and sheep and goats can get Toxoplasma, and pigs, and we can also get Toxoplasma from eating meat that's undercooked that has the cyst in it. So cooking, in terms of prevention, as Harriet is saying, things like cooking meat, making sure that it doesn't Toxoplasma in it is also very important. I think water purification on a worldwide basis and for people traveling being careful about water sources are also other ways that one can prevent this type of infection.

REHMAll right. Let's talk about something even closer to home. And that is cleaning out the kitty litter box. Is there a risk there of somehow an adult who might be immune, being affected by this bacteria and then somehow passing it along to a child?

YOLKENRight. So let me first say about cats...

REHMAnd kitty litter.

YOLKEN...that I have two cats, and I like cats. I say that a lot of things we deal with in society, there are safe and unsafe ways of dealing with them. We have safe driving, safe sex, safe texting. And I think there's such a thing as safe cats. So I think that we can do things that minimize a cat likely to be Toxoplasma positive. The number one thing most people can do is keep their cats inside. Because an indoor cat is extremely unlikely -- it's not impossible, extremely unlikely to get Toxoplasma.

YOLKENSecond thing I think in kitty litter, it is wise that pregnant women not do this, and that people wash their hands afterwards. I think that's probably common sense as well. Keeping your cat well-fed is a good idea, because a cat that's well-fed is less likely to eat a mouse that is going to give it Toxoplasma. And good veterinary care is extremely important. A healthy cat is much more likely to shed than an unhealthy cat. And it's usually kittens are much more likely to shed than older cats are. So I think there are safe and unsafe ways of dealing with cats. And I don't want people to give up their cats. I think there are many benefits from them, but just to take care of them well.

REHMDr. Giordano, do you think that this information has been moving into pediatrician's office perhaps a little more slowly than it should have?

GIORDANOI think it's an interesting balance you raise here. We don't want to rush misinformation into pediatricians or...

REHMRight.

GIORDANO...other physicians' offices because that tends to be alarmist. But I think that the prudent distribution of information, as Dr. Yolken and others have indicated through their research, would suggest that there are defined risks, and also to be a little more sensitive to the onset of psychiatric symptoms in children to suggest that there may be an other organic cause inclusive of an infectious agent. And I think what that does is that just changes the clarity of the lens through which physicians, including pediatricians, may be able to look.

GIORDANOSo I think that the take home message here is we've seen a slow, steady and increasing pace of this research that has had a trickle-down effect into clinicians' offices. And I think that the prudent analysis of this research becomes very important to dictate changes in medical practice that would then allow physicians to look if there has been a precipitating infectious disease, an event, and how these may relate to now only PANDAS, but other forms of psychiatric illness in children, in adolescents and even perhaps in adults.

REHMAnd you're listening to "The Diane Rehm Show." Let's take a caller. Elizabeth in Cincinnati, Ohio. You're on the air.

ELIZABETHYes, thank you. Thirty-one years ago I came home from work not feeling well. It was a viral like illness and expected to recover and go back to work and my life. And I never did recover, and was eventually diagnosed with chronic fatigue syndrome, and bedridden. I've been bedridden, and became clinically depressed. And I'm on antidepressants and anti-anxiety medications. And I've often thought about doing away with myself, and -- because I'm bedridden pretty much. And the doctor, I think it was Yolken, mentioned something about anti-virals and medications now, and I was wondering if there was -- if he knows of anything that might be effective.

REHMAll right. Thanks for your call, and I'm so sorry that you're experiencing this. I've heard from so many people who have experienced chronic fatigue syndrome. Dr. Yolken, do you have any thoughts about that and its possible connection to a virus?

YOLKENYeah, so I'm not an expert in this area, but I have been following it. There's certainly many stories like Elizabeth was saying. You certainly have my condolences and best wishes. You're not alone. There are many other people in your situation. The story often does sound like it's an acute infection that sets it off. The problem has been trying to identify direct effects of viruses in individuals. I think the more likely scenario is that the virus sets off an immune response, which like Dr. Giordano was saying, and then what you're seeing is the effect of the immune response.

YOLKENThis is an area where there's a lot of research both in terms of using -- of trying to use anti-virals if we can identify people where that would be appropriate, and also by variations in the immune system. So I would suggest really keeping tabs on that and seeing if some new immune modulator could, in fact, help you and the many other people that suffer from this.

REHMHarriet, can you speak to what's happening in the research field?

WASHINGTONOnly to say, Elizabeth, I'm profoundly saddened by what's happened to you. And it certainly is my hope that as there's more and more discussion and dissemination of the connection between infectious disease and mental consequences that research will be speeded up and that you will get answers soon, that some treatment will emerge.

REHMDr. Giordano, do you know of research being done in this area?

GIORDANOI personally do not. There's a variety of different groups that are working in the area of what's called neurovirology, as Dr. Yolken was -- and certainly there are a number of groups that are also working specifically on neurological mechanisms of chronic fatigue syndrome. I think perhaps what Elizabeth may need to do is to become sort of a more aggressive consumer of some of that research. There are some wonderful portals out there that are available on WebMD, Google Scholar.

GIORDANOBut I think the important thing to do as well is to really follow-up medically, because the field has changed over the past few years. And I think that some of the advances that are coming out of the research front have, in fact, made their way into the clinical encounter and she may reap the benefit of that.

REHMWell, I hope that she does keep looking and keep on talking with doctors. Thank you all so much for joining us. Harriet Washington is the author of a new book titled "Infectious Madness." Dr. Robert Yolken is at the Johns Hopkins University School of Medicine. Dr. James Giordano is at the Georgetown University Medical Center. Thank you all so much.

WASHINGTONThank you, Diane.

YOLKENThank you. Thank you.

REHMAnd thanks all for listening. I'm Diane Rehm.