The neurology-psychiatry interface

N. SRIDHARAN

Interview with Dr. E.S. Krishnamoorthy.

"Though the interface between neurology and psychiatry has existed as a concept since the 17th century, it is only in the last three to four decades that interest in it has grown," says Dr. E.S. Krishnamoorthy, the Chennai-based behavioural neurologist whose research in the area has contributed much to changing the perception of the interface.

Dr. Krishnamoorthy is vice-chairman and Consultant in Clinical and Behavioural Neurology at the T.S. Srinivasan Institute of Neurological Sciences and Research, Public Health Centre, Chennai, and Chief of Neuroepidemiology and Consultant in Clinical and Behavioural Neurology at the K. Gopalakrishna Department of Neurology, Voluntary Health Service (VHS) Medical Centre, Chennai. He holds the T.S Srinivasan Chair in clinical neuroscience in these institutions and has academic links to a number of prestigious bodies, including the Institute of Neurology, University College, London and the Institute of Psychiatry, King's College, London.

Dr. Krishnamoorthy graduated from Mangalore University in 1992 and has made an indelible mark in the field of neurosciences. He is an executive committee member of the International Neuropsychiatry Association, a member of the International League Against Epilepsy's Psychobiology Commission and chairman of the Sub-commission on Transcultural Aspects and secretary of the International Task Force on Organic Brain Syndromes.

As a Raymond Way Research Fellow in Behavioural Neurology at the Institute of Neurology, London from 1997 to 2001, Dr. Krishnamoorthy looked after the Neuropsychiatry of Epilepsy Clinic at the National Society of Epilepsy at Buckinghamshire and the Neuropsychiatry Clinic for Epilepsy Surgery at the National Hospital for Neurology and Neurosurgery, London.

With over 50 articles, editorials and chapters to his credit, Dr. Krishnamoorthy has edited entire supplements to international journals and has presented cutting-edge research papers at several international conferences, including the Bethel Cleveland International Symposium in Germany and the Fourth Asian Epilepsy Congress in Argentina. He has won several international fellowships and awards for his original work, including the Paul Hamlyn Fellowship from the Paul Hamlyn Foundation, London.

In a recent interview, Dr. Krishnamoorthy spoke to Asha Krishnakumar in Chennai on a range of issues, including the changing perception of the neurology-psychiatry interface, its impact on the development of pharmacology and treatment options, growing research in the area and the impediments to its research in India. Excerpts:

How can one explain, in a layperson's terms, the interface between neurology and human behaviour?

Drawing a computer analogy, we could say that behaviour is the software and the brain, the hardware. The interface between neurology and psychiatry is very broad. It encompasses the perspectives of neurologists (who look at the brain as having an impact on human behaviour), biological psychiatrists (who study different parts of the brain that get affected during varying human behaviour), neuro-psychologists (who look at psychological functions as a product of brain functioning and development) and neuro-psychiatrists (a broad term covering various aspects of the interface). All these areas and the correlations among them constitute the interface between the mind and brain.

Do specialists in different areas in neurology collaborate as a team?

Unfortunately, not always. They tend to remain as individual groups with unique orientations. In major institutions, they interact. But they also retain a great degree of individuality. This is also because the study of the interface is not purely clinical. It is a research-oriented speciality. In an ideal world, specialists in different areas of this interface would work closely.

When did these specialities develop? How are they related to one another?

As disciplines, they are new. They have evolved only in the last three to four decades. But as concepts, they go back to the 17th and 18th centuries or even to the times of Hippocrates, who has written about how brain functions can affect human behaviour.

There was some interest previously in phrenology - relating the measurement of skull morphology and its links to brain function, including behaviour. People got so interested in this that even at fairs one could have one's skull measured and the data processed using automatic machines. Phrenology soon fell into disrepute and interest waned. What makes this historical information interesting is that imaging technology has led to modern phrenology and we now study relationships between areas of the brain and human behaviour using imaging.

Why did the interest in the interface between neurology and human behaviour wane?

Even as early as the 18th century, European literature has a lot on this interface but Sigmund Freud changed all that. From the end of the 19th century to the first half of the 20th century, the orientation became totally psychodynamic or psychological and behaviour started to be explained only by psychological factors such as experiences, relationship with parents and the impact of environment.

Can it be said that Freud's work was a setback in the study of the interface between neurology and psychiatry?

In a way it was. It changed the orientation and practice so much that people stopped looking at behaviour as a function of the brain. Even today, many who deal with psychiatry in the U.S. have a psychological rather than a biological orientation. Then the interest came back.

How did that happen?

That happened for a number of reasons, including the development of treatments and investigating techniques. With the development of drugs such as chlorpromazine (Largactil) that could control aberrant human behaviour, people once again realised the biological link. The advent of psycho-pharmachology was one of the factors responsible for the renewed interest in the interface.

Development of investigating techniques was another important reason for the renewed interest in the interface. Brain imaging, in particular, played a very important role in changing perspectives on the interface.

When did this happen?

While these developments have been going on in the last five decades, CT scan imaging, developed in the late 1970s, later the MRI (magnetic resonance imaging) scan technology in the 1980s and subsequently PET (positron emission tomography) scan really brought about a major change in the field. Since then, there has been explosive growth in the area of brain imaging.

What kind of research studies have been undertaken using the latest techniques of imaging?

Imaging has changed our perspective on the brain-behaviour function. Techniques of volumetric measurement are used to study various brain parts and how alterations in volume correlate with behaviour. The London research group with which I am associated has demonstrated, for example, a number of interesting associations between the volumes of the amygdale and hippocampus (structures critical for emotions and memory) and various behavioural correlates. Other techniques include MRI and PET. People are shown pictures of faces showing different emotions such as distress, anger and fear, and their brain is studied - how they respond and which parts of their brain get activated are analysed and correlated using the technology. Such "real time" scanning has opened up avenues for research.

It is found that certain parts of the brain get active when a person is in love, in pain or in fear. One of the important findings is that psychopaths fail to recognise others' emotions and that is why they fail to empathise with other people or display aggression and other inappropriate behaviour.

Studies have also shown that the human brain is an incredibly plastic organ, much more than neuroscientists imagined. For example, a two-year study involving London cab drivers has shown that the volume of hippocampus, a part of the brain involved in memory, changes as they memorise the London map.

Other interesting findings have been established in anxiety disorder and depression, where certain brain structures appear to be more involved. In the elderly, for example, interesting associations have emerged between cerebrovascular disease (stroke) and depression. From MRI research, it is also becoming clear that patients with schizophrenia and manic depressive illness (bipolar disorder) have significant changes in the brain.

What other research has led to changes in the perception of the neurology-psychiatry interface?

Advances in clinical epidemiology/research have been important. It is being increasingly understood that psychological morbidity strongly predicts outcome in brain diseases. Behavioural factors of patients with epilepsy, Parkinson's and dementia seem to play a significant role in the extent of their disability and recovery. Our group in London has shown, from clinical studies, that psychiatric disorders are over-represented in patients with neurological disease and also that some unique forms of common problems such as anxiety and depression exist in disorders like epilepsy. From a public health perspective, these are important as the link between disability, quality of life and emotional disorders is strong.

There may be unique environmental events early in life (even at the time of conception and birth) that are associated with the development of illnesses later on. Further, changes in the brain have been observed quite early in life and these may have a genetic basis. These findings of brain changes in people with mental illness put a whole new perspective on our approach to these illnesses and are helpful in eliminating the stigma these illnesses are unfortunately associated with.

How do you describe the mind? Can it be related to human behaviour?

When we talk of the mind, we generally touch our hearts. Actually, there is no physical entity called `the mind'. It is actually the chemical, hormonal and neural links within the brain and how they express themselves that constitute the mind.

Our understanding of the mind came from focal brain problems and how they express themselves in human behaviour. For example, we knew that Parkinson's is a disease of the basal ganglia and if we look at persons with the disease, they do have certain common behavioural changes - they tend to be depressed or apathetic, more than normal people. They tend to have more obsessive neurotic personalities that pre-date the disease. Similarly, people with temporal lobe epilepsy have been observed to demonstrate behavioural characteristics such as an increased tendency to write copiously and keep diaries and increased interest in religion. These behaviours can be linked to the parts of the brain that involve Parkinson's disease (the basal ganglia) and epilepsy (the temporal lobes).

Other examples are disorders that affect the frontal lobe - head injuries and certain kinds of dementia. Depending on which parts of the frontal lobes are involved, various behavioural constellations - being apathetic and withdrawn, manic, disinhibited and aggressive - are observed.

To make the diagnosis and to differentiate between various types of behaviour and the associated changes in the brain, is it necessary to have an understanding of the correlations between a particular behaviour and the brain parts that it would affect?

That is a very good question. We increasingly understand now that the brain does not function in parts. It functions more as a sum of parts. There is a great degree of connectivity in the brain. It is not just focal areas that govern certain behaviours, as previously believed, but entire connections - what we call neural networks.

But we know that the left side of the brain governs literary tendencies and the right side, mathematical abilities and musical appreciation. How does such knowledge fit into our overall understanding of neural networks influencing human behaviour?

Yes, certain parts are dominant in certain behaviours. Many of these observations traditionally come from looking at focal problems in the brain. For instance, when there was no scanning, autopsy was done on people who had suffered from similar problems and then conclusions were drawn about which part of the brain was affected. Imaging has changed all that by bringing in a new perception to the study of the interface.

While certain areas may be dominant for specific functions, the functions may involve several areas. If the problem, say a tumour or an infarct (area of cell death owing to poor blood supply) affected one of these associated areas, a subtle variant of the problem - a sub-syndrome - may manifest.

Have the changes in perception about the interface improved or changed treatment options? Has pharmacology benefited from changes in our perceptions.?

Certainly an increased understanding of chemical and hormonal systems in our brain has led to the development of many drugs. But, at the moment, a lot of psycho-pharmacology is generic to the brain. We know that certain chemical systems are over-represented in certain parts of the brain but our knowledge has not gone beyond that. When we get to a stage where we develop treatments that do not just target certain chemical systems but target the neural networks that are involved in the illness, then we would have made a difference to treatment options. Given the pace and rapidity of research in this area, [that stage] may not be too far.

How important are genetic factors in understanding the interface?

The human genome project is a major advance in our understanding of the role of genes in illnesses. What is apparent is that many of these illnesses are polygenic, which may be subject to environmental influences and the solutions are not going to be simple. While single-gene disorders (sub-types of well-defined existing neurological and psychological illnesses) have been sorted out, polygene disorders will take time.

How do environmental and social factors influence human behaviour?

While the biological link between the brain and human behaviour is exciting, undoubtedly behaviour is a product of psychological experiences and the environment. Indeed, the recommended approach to understanding and managing behavioural disorders remains bio-psycho-social. An analogy can be drawn between cigarette smoking and lung cancer. Not everyone who gets lung cancer is a smoker and not everyone who smokes get lung cancer. But there is no doubt that the risk of lung cancer in a smoker is manifold, indicating a gene-environment interaction. Similarly, if you were born with a certain genetic and neuro-chemical makeup that increases the risk of a behavioural disorder or if you suffered certain neuro-developmental insults (for example, birth injury) or if certain adverse psychological and social circumstances overtook you during the course of life, then it may lead to the development of behavioural dysfunction. This is a bio-psycho-social model that many neuroscientists subscribe to.

Once you take the line that environment has a profound impact on behaviour, how can you generalise on the interface between the brain and behaviour?

You cannot. That is one of the criticisms of this area. A lot of imaging research is done on very small samples. Also normative data is often lacking. With each research group collecting its own normative data, it is too small to be making major inferences.

There are no ready solutions to these pitfalls. Ideally, large epidemiological studies need to be linked to brain imaging and genetics but this is very expensive.

Does the interface change with gender, ethnicity, cultural factors and so on?

There will undoubtedly be differences between men and women as there are anatomical, physiological and chemical-hormonal differences between them. There are also trans-cultural differences. Since a lot of research is done only in developed countries, we hardly know about differences in other populations. All the information we have now is going to make it very difficult to generalise.

Also, the nature of imaging studies is such that one cannot have large numbers as it is financially and practically not viable. A lot of energy is wasted in trying to make statistical sense of small sample sizes.

From a developing country perspective, it is important to understand how psychological status is going to impact how disabled one is with neurological illnesses. In India, there is very little recognition of the brain-psychology interface.

Why is there little interest in research on the interface in India?

This is because of a number of reasons, including limited awareness of the interface even among the medical fraternity. Teaching of the interface at the post-graduate level is also limited. The other problem is that the technology involved is expensive and not readily accessible. Even if it is there, it is often out-dated. It is very hard to keep pace with the West, especially when working on a technology platform.

But we can contribute strongly in clinical research. There are a number of illnesses, such as infections, which are over-represented in India. We do not know too well the consequences of brain infections. That is where we can contribute.

What inhibits clinical and epidemiological research in India?

Getting funds is not as major an issue now as it was a decade earlier. The main problem is that in speciality national institutions, doctors are often so busy taking care of patients that they hardly have time for research. Unlike developed countries, which insist on referrals, we take walk-in patients in national centres. What we do not have is `systems in place'.

Why do we not have systems? How can it be brought about?

There is no national health care system. This means that there are no tiers or pathways that everyone follows. Countries with a national healthcare system are better organised for research, though the quantum of research in the U.S. shows that this may not be wholly essential. We do need systems that track down patients for their own healthcare needs and for research. The other limitation we face is the lack of proper maintenance of patient records, making it very difficult for researchers.

The lesson learnt over the years is that healthcare cannot remain totally private or public. There are countries that have effectively worked out combinations. Unless we move into cooperative and tiered healthcare, we will never be able to overcome the impediments to research.

What is your recent research study in India?

We are looking at the psychological burden in neurological illnesses and setting up registries of patients with neurological illness. We are trying to work out culturally-sensitive ways of assessing the quality of life. We are working on developing a comprehensive range of social measures that we will use in the study of patients with neurological illness.

The other area we are working on is to see how psycho-social interventions can improve outcomes in neurological illness. We are part of the international 1066 Dementia group consortium sponsored by the WHO that is looking at the care-givers model.

We are also looking at what influences `human will' using imaging. We are developing a test for will and we plan to study it in conjunction with real time functional imaging.

What are the treatment options in countries like India?

Interface problems need a multi-dimensional approach. Thus, from a public health perspective we need to organise ourselves as teams.

We have only 500 neurologists and 2,000 psychiatrists for a country as large as India. Most of them are concentrated in cities. One needs to look at other ways to reach out to the masses. For instance, training primary-care physicians or having specialised nurses who can tackle a range of these problems. At the moment none of these exists and very few initiatives are on.

Considering that by 2050, most of the dementia patients will be from the developing world, there is a great urgency in addressing these public health issues.