Medscape: How would you describe OCD?
Dr. Rapoport: Obsessive-compulsive disorder is a disorder in which thoughts and doubts and personal rituals run wild. It is a crippling disorder that, in its severe form, can ruin people's work and personal lives and have a devastating effect on their families. People use the words "obsessive" and "compulsive" to mean that they are somewhat neat or they like to be early for trains or airplanes, but that is not what OCD is about. The person with OCD typically has irrational obsessions about contamination, checking, or guilt. The person is sure that he did not wash well, that he has some terrible illness that, in reality, he is at no risk for having, or that he is contaminated by anything from detergents to walking near someone who has an illness. The thoughts are recognized as irrational, yet the person cannot seem to help his preoccupation about them.
Rituals are things like washing, avoidance, cleaning, checking, strange ways of walking or moving, which are sometimes tied to obsessional thoughts.
Another unusual aspect of this disease is that about half of the people who get OCD get it before age 15; so, it is of great interest to child psychiatrists as well as adult psychiatrists.
Medscape: What is the incidence of the disorder?
Dr. Rapoport: It is much more common than was thought 20 years ago. Surveys in certain countries have had it at 1%, putting it closer to the rate of schizophrenia. Some surveys have even shown a level of 2% to 3%.
Medscape: Your work has radically changed the way OCD is perceived. Please discuss how and why that is.
Dr. Rapoport: Some classic writing suggested that OCD might be a psychological condition. But a lot of converging bits of information pointed to this as a disease of brain functioning. For example, my research group and I noted that among children with OCD, particularly boys, a very high percentage had motor tics and several went on to have Tourette's disorder. We were among the first to note that there was a genetic relationship to Tourette's disorder. Whether the person with tics has OCD, or the person with Tourette's syndrome has obsessions, it goes together in families.
Around this same time, some of the brain imaging techniques used today were introduced. Our research group was also among the first to show that those with OCD have an increased metabolism in parts of the brain -- namely, the orbital frontal cortex, the caudate, and part of the basal ganglia.[2,3]
Everything came together, and all of a sudden, this supposedly very psychological disorder has become among the best studied neurobiologic disorder.
Medscape: And this different way of thinking about OCD has affected the way it is treated?
Dr. Rapoport: Absolutely. The treatment formerly recommended was insight psychotherapy, which does not have a helpful track record for OCD. But with the enormous increase in recognition of the neurobiology came parallel lines of study. One is the use of drugs, first clomipramine (Anafranil), and then all the other serotonin drugs that came after it, such as fluoxetine (Prozac) and sertroline (Zoloft).
The other was the increase in recognition that behavior therapy was very helpful. That takes a little explaining, because people often use the word psychotherapy to mean many different kinds of non-drug treatments and even behavior therapy has many different kinds of treatments. Weight Watchers, relaxation training, and biofeedback are all behavior therapies, for example, but they do nothing for OCD.
The treatment for OCD is a kind of behavior therapy where the person is exposed to the trigger that sets off the obsession (such as dirt) and then to response prevention, where the person is not allowed to wash for several hours after this exposure. Doing that daily for at least 1 hour over several weeks does bring improvements. The twin findings that behavior therapy worked, and drug treatment worked, have led to resolution of a majority of cases.
Medscape: How often does the treatment work?
Dr. Rapoport: Seventy percent of people who try one or both of these treatments get substantial help. That statistic lumps together people who have tried 2 or 3 different drugs to find the 1 that works best for them, people who have had behavior therapy, and people who have had treatment with both drugs and behavior therapy. This number does not necessarily reflect OCD patients trying just 1 drug and sticking with that, or just doing behavior therapy.
Medscape: Does the fact that OCD responds to either behavior or drug treatment tell us anything about the nature of the disorder?
Dr. Rapoport: Well, that is an important question, and it may be that there is more than one way to reset brain chemistry. Our research group showed that people who respond to clomipramine have a decrease in the caudate nucleus metabolism. More specifically, patterns of cerebral glucose metabolism measured by positron emission tomography (PET) scan go from glowing much higher than the controls to looking quite a bit like controls in particular regions of the brain. There was a classic study done in the 1990s at University of California, Los Angeles (UCLA), showing that behavior therapy has the same effect, suggesting that both chemical and nonchemical agents can change brain chemistry, and that the brain is capable of learning different patterns.
Medscape: Behavior therapy involves a retraining. What happens with the drugs? Are they effective only as long as the medicine is on board?
Dr. Rapoport: Most people would say that the drug is only temporary -- while the patient is taking it, and that behavior therapy tends to have better transfer to the months after the treatment ends. But I believe that the drug treatment has lasting value as well because it enables people to do their own do-it-yourself behavior therapy -- in other words, being exposed to triggers and not avoiding them while on the medication. They take more risks, get more exposure, no longer avoid going to an office where they might get germs, etc. The drugs allow people to perform these otherwise anxiety-provoking behaviors every day.
Medscape: Given the growing understanding of OCD as a brain disorder, is it increasingly perceived as different from anxiety?
Dr. Rapoport: There is a lot of debate about that. OCD is currently classified as an anxiety disorder, which is not all wrong because these patients become very anxious at the notion of contamination or guilt; but, that classification does not feel quite right. Part of the problem is that, when reviewing the other diagnoses, there is not such a clear place to put OCD. It does not track so much with the other diagnoses. It is very clear, for example, that if a person has a phobia, he may be more likely to have generalized anxiety disorder or something like that. That is not necessarily true of OCD. OCD is comorbid with a variety of conditions including Tourette's syndrome, attention deficit disorder, and depression. It has broad comorbidity across several different categories of disorders. Experts, therefore, are not happy with the anxiety category, but they do not agree on another place to put it.
Medscape: How do the findings on OCD help define it in contrast to other disorders?
Dr. Rapoport: The specificity of the treatments is not so clear. The drugs that help OCD tend to be pretty good for depression and anxiety of other kinds.
In brain imaging studies, the circuits between the basal ganglia and the frontal lobes seem to come up over and over in a number of different disorders; for example, other anxiety disorders, attention deficit hyperactivity disorder, Tourette's disorder, maybe some of the mood disorders. There is some specificity for the patterns, and people are impressed with subtle abnormalities of the orbital frontal and the caudate in those with OCD, but there is still a puzzle as to how much is nonspecific and what areas are specific to OCD.
On the other hand, when researchers have done some linkage studies, looking for genes using deoxyribonucleic acids (DNA) in families of people with OCD, they seem to have a locus on chromosome 9 that does not seem to go with the other disorders.
Medscape: Has research told us more about the role of serotonin in OCD?
Dr. Rapoport: Everyone agrees that serotonin seems to play a role. There have been other studies for people who get only a partial response to a serotonin medicine, showing that someone can take a very low dose of a second kind of medicine -- a dopamine blocker -- and get much more of a response, or sometimes even convert from being a non-responder to a responder. For a good chunk of patients, maybe 25%, the addition of this dopamine-affecting drug may be important. Dopamine and serotonin have a sort of seesaw relationship between each other and the brain, so this may be saying something about the relationship of dopamine to OCD.
There have been a series of studies in the last 5 to 7 years using spectral magnetic resonance spectroscopy in which levels of different chemicals within the brains of those with OCD has been shown; the results point to the possibility that there are differences in the brains of OCD patients with respect to the neurotransmitter glutamate. Based on that question, there is a research study at Yale on a glutamate receptor drug that, by report, is also having some effect on OCD. The effect is not strong, but it may be effective for some patients.
Medscape: There seems to be a lot of ongoing research. Can you comment on some additional significant findings?
Dr. Rapoport: One of the subgroups of OCD currently under investigation is a group called pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection or PANDAS. These are young children with OCD who often have tics as well. While controversial, there is some evidence that a small number of very vulnerable children may develop this condition in response to streptococcal infection. The antibodies may attack the caudate, the basal ganglia, or another area of the brain that seems to be involved much of the time.
Another, very different, type of research regarding the treatment of OCD is one of the last strongholds of psychosurgery. The ideal double-blind controlled studies have not been done to test this theory, but some experts think that there are convincing case reports of extraordinarily severe cases of OCD being helped by a particular surgical procedure. The lesions created by the operation interrupt the hyperactive circuit between the basal ganglia and the frontal lobes, the caudate and the orbital frontal cortex specifically.
There is a later, reversible version of this procedure called deep brain stimulation that involves placement of an electrode directly in the brain. This approach has been very helpful for Parkinson's disease and for movement disorders, like dystonia. It may also help treat OCD.
Medscape: Is there anything else you would like to add?
Dr. Rapoport: The change in this area of study has been amazing. For one thing, when we started working on OCD, people were not coming and asking for help, probably partially because they were feeling that there was not anything out there that could help. Now, there are so many available resources. There is a Web site with a nonprofit patient support group called the OC foundation that gives names of clinicians and clinics. There are now hundreds and hundreds of OCD clinics. Every academic center has an OCD program for children as well as adults. There are now 6 drugs on the market, and more are being researched. Oh, I could go on and on. To see all of this change has happened over a relatively short time, as far as the history of medicine goes, has been enormously gratifying; I am very proud to have been associated with such progress.
This interview is published in collaboration with NARSAD: The Mental Health Research Association.
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