MEDICINE

An expanding interface

Interview with Dr. E. S. Krishnamoorthy.

Neurology and psychiatry may have started off like chalk and cheese - the first very precise and the second abstract - but over time the differences have blurred and solutions to many of the neurological and mental illnesses lie in the interface between the two, says Dr. Ennapadam Srinivas Krishnamoorthy.

The Raymond Way Research Fellow in Behavioural Neurology at the Institute of Neurology, Queen's Square, London, a major centre of neuroscience and one of the most famous medical institutions in the world, Dr. Krishnamoorthy (32) has had unique training combining psychiatry with behavioural and clinical neurology.

Having acquired his graduate medical training and post-graduate qualifications in India, Dr. Krishnamoorthy went on to train in neurology at Queen's Square, and then at Newcastle-upon- Tyne in northern England, another neurological centre of excellence. He then returned to the Institute of Neurology in London to occupy his present position. He is currently working on his doctoral thesis on the epidemiology of psychiatric disorders in epilepsy, at the Institute of Neurology, and is involved in a number of research projects studying behavioural aspects of neurological disorders such as epilepsy and Parkinson's disease. Dr. Krishnamoorthy has also authored many scientific papers in this area.

Recipient of a number of awards including the Paul Hamlyn fellowship for post-graduate training in neurosciences, Dr. Krishnamoorthy is a member of the International Commission on Epilepsy and Psychobiology set up by the International League against Epilepsy. In Chennai recently on a lecture tour, Dr. Krishnamoorthy spoke to Asha Krishnakumar on the relevance of the interface between neurology and psychiatry, its applications in research, and importance in the Indian context. Excerpts from the interview:

What is the relationship between neurology and psychiatry?

In general, neurology and psychiatry are like chalk and cheese, very different from each other. Neurology is a very logical specialisation, mathematical and analytical. It has clearly defined rules and guidelines. And if you understand the brain and anatomy of the nervous system you can mathematically, following principles of logic, make a diagnosis.

Psychiatry, on the other hand, is entirely abstract or at least perceived that way. And it is in some ways a speciality that is infamous for that reason. It is not very precise, and until some time ago it did not have very clear rules and guidelines. It was very individualistic, so much so that it was and perhaps still is considered as much an art as it is a science.

In conventional terms that is the difference between psychiatry and neurology. But in the last three to four decades these boundaries have become blurred and the distinctions are no longer so clear. We now understand quite clearly that much of human behaviour is the function of the brain. At least we are now quite clear that most psychiatric disorders are due to brain dysfunction. This has led to a very interesting interface between the two specialities. On the one hand you try and understand the biology of psychiatric diseases - that there are abnormalities in the brain and the nervous system that are observed in most major mental illnesses. Some examples of this are schizophrenia and manic depressive illness. We now understand that in these disorders there are genetic and developmental factors that impact the brain.

On the other hand, behavioural disorders were not considered an integral part of most neurological illnesses. But we now understand that in many of these conditions there is a specific behavioural component.

Epilepsy, movement disorders such as Parkinson's disease, headache and pain disorders, multiple sclerosis, are examples of neurological conditions with associated behavioural manifestations. Thus the interface between the two specialities is considerable.

When did the differences between the two specialities begin to blur?

The history in this area is rather interesting. The ancients including Hippocrates believed that all psychopathology arose in the brain, and this is clearly reflected in the writings well into the 19th century. An extreme version of this belief was the development of phrenology under which, essentially, external measurements and qualities of the skull were correlated with abnormalities of behaviour.

Then came the era of Sigmund Freud and the birth of psychoanalysis. Freud, his followers and generally the world after that, for nearly half-a-century or more, went on to focus on psychodynamic aspects of mental illness, and psychiatry was drawn away from neurology. With the advent of drugs that could treat mental disorders the scientific world once again took an interest in the role of the brain in mental illness. In the last three or four decades advances in molecular genetics, immunology and in particular brain imaging have led to rapid strides in our understanding of mental disorders and have brought neurology and psychiatry closer than ever before. The scope of the interface is now vast and constantly expanding.

What is the clinical scope of this interface?

When you examine this interface between psychiatry and neurology the areas that are of interest to the clinician and demand his attention are the psychiatric aspects of neurological disease and the neuro-biological aspects of psychiatric illness. There are also the great pretenders; psychiatric disorders that manifest as a neurological problem, and perhaps even more importantly, neurological disorders that manifest as psychiatric illness. A very good example of the former is the problem of non-epileptic seizures. These are attacks brought on by depression, anxiety or stress. Even for the informed observer it can be difficult to distinguish these from epilepsy, and often video-EEG (electroencephalography) is necessary to make this distinction. One in every five persons diagnosed to have epilepsy has non-epileptic seizure. They are misdiagnosed to have epilepsy, and exposed to inappropriate treatment with the risk of side effects. A very good example of the latter are brain tumours that present themselves with predominantly behavioural manifestations, and are misdiagnosed and even treated as psychiatric disorders. This can be potentially life-threatening. There are also illnesses such as dementia that fall squarely within the ambit of this interface. To diagnose and manage this condition effectively, both neurological and psychiatric skills are required.

In many countries including in the West, the problem is that most psychiatrists are not conversant or comfortable with neurology. The same is the case with neurologists with regard to psychiatry. As a consequence the patient is often referred from one specialist to the other and the treatment is often sub-optimal, especially when cases fall within the ambit of this interface.

In the West, to a large extent the referral centres are able to cover this area. In India we do not have, to my knowledge, any academic centres which have specialist clinics or facilities dedicated to this interface. There is, thus, a huge vacuum. This, I think, is going to be very important in the future.

Why do you think this is going to be important?

There are many reasons. Let us consider the dementia example again. About 5 per cent of people over the age of 65 and 20 per cent over 85 suffer from dementia. Its incidence increases as you get older, which means as people begin to live longer the illness is going to become more common. Medical advances are beginning to ensure that people live longer, and this is not merely a Western phenomenon. You would therefore expect dementia to become more common in the future. Combine this with the social changes that are taking place. In India the family has been the backbone of support to the ill person, in the absence of social provisions for care. The break-up of the joint family system, an increased tendency to migrate to other places in the quest for careers and so on have resulted in, at least in the urban milieu, many old people having to live on their own. Thus, while in the past if an elder in the family lost certain faculties he would be supported by the family, in the changed social milieu, many old people end up living alone - the children have moved away to work, and so on. In such situations, any deficiency in mental faculties becomes very apparent. Socially, and as a public health problem, we are not yet prepared to deal with this. Further, as we do not have facilities that combine neurological and psychiatric skills, effective diagnosis and treatment of such conditions are going to be difficult.

Are not neurology and psychiatry taught together?

N. BALAJI

In many parts of the world there is a deficiency in training. Doctors engaged in post-graduate training in either speciality do spend a short period of time training in the other. However, the extent of training in the subsidiary speciality is limited, and the level of clinical responsibility assumed inadequate, for this to be effective. To be an effective clinician-scientist in this area, one needs to divide one's time equally between neurology and psychiatry, as some residency programmes in the United States allow, or to develop a background in one speciality, onto which the other is grafted through extensive training and hands-on experience. I have spent a significant amount of time in the two disciplines before dealing with the problems falling within this interface. This is what everyone in our group is trained for, and that I believe is absolutely essential.

What is the focus of your own research?

I am interested in the psychiatric aspects of neurological disease. A question that has not been answered satisfactorily despite many years of research is whether psychiatric disorders are more common in patients with epilepsy. This has tremendous implications both for the patient and his management and for our approach towards epilepsy as a public health problem, for the planning and establishment of resources and so on. This area of research is called epidemiology, and studies the distribution and determinants of disease in the population. I am looking at the epidemiology of psychiatric disorders in epilepsy. As epilepsy is a common neurological disorder and thus a public health problem of significant proportions, this becomes important. Studies have shown that 40 to 50 per cent of people with epilepsy suffer from common mental disorders such as anxiety and depression. About 10 per cent (of those afflicted with epilepsy) are estimated to have major psychiatric disorders such as schizophrenia and manic depressive illness. These figures, however, need further validation before they are accepted. Epilepsy by itself has been shown to have a significant effect on quality of life. Living with epilepsy and a mental disorder can obviously be rather daunting.

Does epilepsy lead to major psychiatric disorders?

It is not clear whether one leads to the other, but they certainly co-exist. We also know that there are certain psychiatric disorders unique to patients with epilepsy. In that sense there is perhaps one causative or common pathology that is causing both illnesses. Indeed, there is some evidence to suggest that a common pathological process can lead to both illnesses. For instance, the part of the brain called the hippocampus is implicated in many cases of epilepsy, and has been shown to be abnormal in patients suffering from schizophrenia. It is possible that these conditions have common biological origins in the brain.

Another area of research that I am interested in is the lack of will or the inability to perform what is in the mind. This phenomenon called abulia has been observed in both neurological and psychiatric disorders.

Other areas of research interest include the role of the part of the brain called the amygdala in the development of psychopathology, studies of neurotransmitter systems in neuropsychiatric psychoses using functional imaging and so on.

What is the present state of the research in this interface?

Essentially there are four very important areas of research. The first is animals, where you try to understand normal and abnormal human behaviour based on animal models. The advantage obviously is that it is possible to study animal models in ways that are not possible with human subjects. While it may not be possible to transpose findings from animal models directly on to human behaviour, these models do to a very large extent help in improving our understanding of human psychopathology. Animal research is also helpful in the development of drugs that treat these disorders.

Another area of importance is laboratory-based research on human tissue examining biochemistry, pathology, immunology, molecular biology, genetics and so on. There is a growing understanding that many disorders that fall in this interface have clear associations with genetic and developmental factors. There are also changes in brain chemistry that are associated with these disorders, and perhaps are responsible for both the neurological and psychiatric manifestations. A case in point is schizophrenia. We now understand that far from being a disorder of the "mind", schizophrenia is a neurodevelopmental disorder with distinct changes in the brain pathology.

The third area is imaging. This has taken huge strides in the last 10-20 years. Much of this is to do with the development of functional imaging, whereby you can see how the brain works. Perhaps the most important of these techniques is Positron Emission Tomography (PET). The others are Magnetic Resonance Imaging (MRI) and Magnetic Resonance Spectroscopy (MRS). The other kind of imaging is Single Photon Emission Computed Tomography (SPECT). These imaging techniques are becoming very important in understanding human cognition and behaviour. The advantage that some of these techniques, PET in particular, have is that they make it possible for us to see which areas of the brain are activated when we are engaged in a memory task for instance, or perceiving a certain emotion like fear. It is becoming possible to understand how the brain actually works.

The fourth area of research interest is epidemiology, which studies the distribution and determinants of illness in the community. This is clinical, that is, patient-based research done with better guidelines, standardised instruments and, most important, with efforts to limit bias. If you go to a hospital and identify 100 people with epilepsy, their problems do not necessarily reflect those of the average person with epilepsy living in the community. That is because people going to hospitals generally have more severe forms of epilepsy. It is therefore difficult to make an accurate assessment of public health needs based on this. This is only one form of bias. There are several such elements of bias that creep into any form of research. What needs to be done is research with as little bias as possible. Epidemiology uses standardised tools of assessment and better scientific principles to understand diseases as they exist in the community.

What is the status of such research efforts in India?

In India, we have a wealth of clinical material as also scientists. We have some of the oldest neurological and psychiatric post-graduate training programmes in this region.

There is quite some epidemiological research activity both in neurology and psychiatry in India. Unfortunately, save a few exceptions it is confined to major institutes. Such activity needs to spread to smaller institutions and regional medical colleges and centres. And instead of replicating work that is done abroad, we should be trying to see what we can do based on our skills and the facilities available with us. For example, infections abound in India and we have many communicable diseases, with neuropsychiatric manifestations or presentations. The not-so-uncommon example is typhoid. It can have very prominent neuropsychiatric manifestations. Tuberculosis is another example. In fact in both the involvement of the brain due to the disease and the drugs used to treat the condition can lead to very prominent neuropsychiatric manifestations. The presentation usually is with a certain degree of confusion and lack of awareness. Apart from that, the person can also have a mood change and become deluded and start hallucinating. These neuropsychiatric manifestations are not uncommon in the case of many communicable diseases. And very often the primary cause may not be apparent when the person presents himself to the doctor; indeed he may be mistakenly diagnosed as psychiatric. People are from time to time admitted to a psychiatric ward before the organic cause for their symptoms becomes apparent. Infections are just one area of neuropsychiatry where we in India can play a significant role in the improvement of scientific knowledge.

To do this, we have to recognise that clinician-scientists are important and that we should encourage their continued development and progress in areas of research that are relevant to us. Investment from the private sector and the support of philanthropists become important, as government funds are often limited and the priority for their use lies elsewhere. It is also important that we encourage a climate that fosters such development. Both the establishment and the public need to realise that scientists in any field, perhaps more so in medicine, need to be adequately compensated financially in order to be able to contribute to science. We should also try and develop training programmes, at least in the major institutes, which allow doctors to train in both neurology and psychiatry, and this should include a strong research orientation rather than the "also research" attitude that currently predominates.

How does India compare with the West in terms of medical technology?

Facilities in India are comparable to many other countries in terms of diagnostic technology. Modern forms of imaging are available in many Indian cities and towns. The difficulty is that these facilities are mostly available in the private sector and therefore are not very affordable for the average person. But when it comes to research, India does not probably have the facilities required to do state-of-the-art research. Functional imaging, for instance, is very expensive and currently has limited clinical applications. It is also expensive to maintain. We could perhaps develop such facilities in one or two centres.

Has pharmacology kept pace with the developments in research and technology?

Drugs are being constantly developed for various neurological and psychiatric disorders. In a sense pharmacology has kept pace with technology and research. We are still a long way from finding the cure for many disorders, but we do have better drugs today that control illnesses and give the patient a better quality of life than we did in the past. In the area that I work in, improvements in our understanding of the way the brain works have led to drugs that target different systems. We have new drugs for schizophrenia, for instance, which target different mechanisms in the brain. Earlier abnormalities in a brain transmitter called dopamine were the focus. The focus now is also on other transmitters such as serotonin.

That has come about through neuropsychiatric research and with this newer and perhaps more effective drugs have been developed. Similar developments have taken place in disorders such as epilepsy and Parkinson's disease.

The major change, however, is generally not in the efficacy of the newer drugs but in their improved side-effect profile. An important consideration while prescribing a drug is the side-effects that the patient may experience, and these often determine the choice of the drug. Perhaps the most important reason for non-compliance among patients is the unacceptable side-effects. One of the big advantages of the newer drugs is that they manage to minimise side-effects. And while they are expensive, it will be difficult to do away with them.