Herbert Pardes, MD, President, Scientific Council, The Brain & Behavior Research Foundation

 

Psychiatric illness is a complex area where much more research is needed in order to improve and tailor treatments for sufferers. Herbert Pardes, MD, President of the Scientific Council, offers his assessment of what needs to be done, and how NARSAD Grants are helping

 

What is the overall aim of the Brain & Behavior Research Foundation. Has its mission changed since its inception?

The aim has always been to improve our understanding of the causes of psychiatric illness and to develop better treatments – that is and will remain the aim of the Foundation forever. Has it changed? It’s influenced by the way the field evolves – so if the field starts saying, for example, we should be doing more in terms of genetic studies or linking genetic factors to specific neurotransmitters, then we’ll see more applications coming in these areas.

A world without mental illness would transform the human race. Do you think this is a realistic goal, and with so many different reasons for mental illness, how can the Foundation eradicate it?

I believe in setting goals that stretch what you do. So can we imagine seeing a world without mental illness in the very near future? That seems like quite a stretch. But to say that’s what we want to do, that we want to get rid of this scourge that affects so many people, that’s right on target. We certainly have made significant progress in treating mental illness in comparison to say 100 years ago when there was virtually no treatment – it’s getting better step by step.

How well are the complexities of schizophrenia, depression, anxiety, bipolar disorder, autism, attention deficit hyperactivity disorder and many other psychiatric diseases currently understood?

Illness in general is very complex. Take the number of years we have been studying diabetes, hypertension, various types of cancer, and we’re still trying to understand their causes. Research is tough. That’s true of psychiatric illness as well. At one point, nobody thought genetic factors were of any consequence. Today it is widely accepted that genes play a contributory role; different kinds of genes, and different kinds of interactions.

We have made progress, but one of the things that is very attractive for me to see is that there are far more good psychiatric research programmes around the country today than in the late 70s and early 80s when there were very few. Today, some 25 years later, almost every academic medical centre of any consequence has a psychiatric research effort. That said, we’ve got a long way to go. To take a comparable example, ‘the war on cancer’ began decades ago and we’ve moved from 5 per cent of children to 65 per cent who recover from cancer. I wish we could make it go faster, but it’s tough and is also a function of how much money we get to support the research.

It’s not an either-or between drug development or understanding the causes; we need all kinds of research: psychological factors, psychological treatments, better pharmacological treatments with fewer side effects, brain imaging, epidemiological studies, brain science studies, molecular biology, genetics – you name it.

How do the brain and its component parts potentially differ in people with mental illness?

That’s what’s being studied now. For example, we are looking at whether the size of different parts of the brain is smaller or larger; do they change in size over a period of time; are there aspects of brain structure or tissue that are predictive? Researchers have many different approaches to this. One interesting one is to look at genes in relationship to specific aspects of structural function in the brain. Instead of looking for the gene for schizophrenia, I may be looking for the gene for dopamine or one of the dopamine receptors – there is a certain refinement in the nature of research that is more accurate and precise.

What has the Foundation’s research revealed about the relationship between genes, the environment and mental illness? How closely are they linked?

I think the relationship between genes and the environment is very important. Years ago it was shown that both identical twins had mental illness much more often than fraternal twins. But that was not always true – sometimes one had the illness and the other did not. What is that other interaction? The environment and congenital or genital factors are very important. A long time ago, Rene Spitz showed that if you put a child into a deprived enough environment, it will have a profound effect on how the child develops. I think the ticket to understanding what we call the major mental illnesses – schizophrenia, bipolar disorder, etc. – probably involves many diseases and many genes. That’s an important way to approach it. It’s like mental retardation. What once seemed to be one illness turned out to be many, and the change is an illustration of the increasing sharpness and differentiation in understanding an illness. We’re working toward having a much more differentiated set of diagnostic categories.

To what extent do you focus on research involving mental illness in children? Is this increasing or are we just more aware of it now? What might be the reason for these changes?

The Brain & Behavior Research Foundation is very much interested in diseases in children and we support it heavily. Of course, what we support is also a function of what the field submits in terms of grant applications, but the issues of psychiatric illness in children are important – both to look at those illnesses in children and also to understand how a psychiatric illness develops. Are there manifestations of it early in a child’s life? How can we trace the development and progression?

Are psychiatric illnesses more frequent in children today? I think it’s mixed – there may be more occurrences but it’s also that we are better at recognising it. Certainly Autism seems to be a combination of those things.

What success has the Brain & Behavior Research Foundation had in developing new drugs and/or rehabilitative approaches to care for people with mental illness?

The Foundation has had an impact on all aspects of mental illness. One of the nice things about NARSAD Grants is that we do encourage as much flexibility and creativity as possible on the part of scientists in what they want to study. NARSAD Grants had a role when clozapine was developed, now involved in many of the brain stimulation techniques being developed today – transcranial magnetic stimulation and deep brain stimulation. NARSAD Grants really reflect what is going on in the entire psychiatric research field, particularly focused on mental illness. I think we’re a little more focused on biological and brain kinds of approaches with NARSAD Grants, and whether that’s a function of the field and the vigour of the biological and neuroscientific vs the psychological applications is a legitimate question. But NARSAD Grants support all good research approaches when they have an impact on better understanding and the development of better treatments for mental illness.

Do you think there are as yet uncharacterised mental illnesses emerging?

That’s not impossible to conceive. Certainly as people age, we see illnesses that were relatively infrequent before developing now. There are certain kinds of brain diseases that are better known now – Alzheimer’s, Autism, etc. You can never say that this field is stagnant. But if you have people living to 80, 90, or 100, when in 1900 the life expectancy was 47 years – that immediately suggests there are going to be differences in the types of things you see. Back in the 70s, Alzheimer’s was not recognised as a distinct disease. It was thought that everyone developed dementia to some extent and became senile. In those years some outstanding neurologists and other scientists showed that this is a separate, specific illness.

To what degree is the Brain & Behavior Research Foundation working to break through the stigma attached to mental illness?

The Brain & Behavior Research Foundation is not directly attacking the issue of stigma, but the more that it helps create a respected, solid group of outstanding researchers and increases the amount of research – and encourages the interaction between different types of researchers – the more the stigma is likely to diminish. We are very proud that we support any and all disciplines – neurologist, psychologist, sociologist, pharmacologist, biochemist – from all over the world. NARSAD Grants foster a large scale, open, collaborative effort with as many people as possible to get rid of the scourge of mental illness. As we’ve seen from the World Health Organization, the impact of mental illness on people’s daily functioning and life is probably the most significant determinant in terms of illness we know.

We have also developed and continue to support the Schizophrenia Research Forum website – a virtual community of scientists collaborating in their quest for causes, improved treatments, and better understanding of schizophrenia. We fund 100 per cent of its work and it has become the dominant online presence for timely, issue-orientated information on schizophrenia research beyond its target audience of researchers to a worldwide audience of consumers, family members, clinicians and other mental health professionals (http://www.schizophreniaforum.org/).

By what means are Foundation-funded scientists benefiting from the Human Genome Project?

The Human Genome Project was extraordinary in that it laid out this poorly understood and yet critical part of the human body. The power and potency of genes can’t be overstated, and this has led to further developments such as the ability now to understand an individual’s human genome. So efforts are being made to correlate whatever the person may suffer in the way of symptoms or illness with key genetic factors. If you find the same cluster of genetic factors repeatedly appearing with similar psychological or psychiatric symptoms or diagnoses, you’ve got good clues as to what cluster of genes to go after. I think the Human Genome Project will continue to spin off productive results for a variety of research fields and was one of the great accomplishments of the last 20 or 30 years.

With stresses on our environment growing and financial worries soaring are we on the edge of a global mental illness crisis? To what extent is our diet and lack of exercise in the developed world exacerbating these issues?

There is a worldwide tendency to see increased psychiatric illness compounded by the economic situation. I believe that we are seeing large numbers of people affected by these environmental factors, whether it leads to anxiety, depression, or suicide. It is there and it is growing. I would like to encourage the development of a new Presidential Mental Health Commission to look at where we are in mental illness and to determine how we can plot an intelligent and constructive course for the future. I think to improve people’s health in general, taking good care of yourself is very important. I think for psychiatric and non-psychiatric illness alike, if you have a reasonable diet, if you exercise regularly, if you don’t smoke, and if you don’t drink to excess, you’re going to have a better life. And to whatever extent those factors contribute to psychiatric problems that will be one less negative factor working against you.

Do you think the medical profession is adequately funded and supported to respond effectively to the effects of mental illness?

I think we should applaud the people who have supported the Brain & Behavior Research Foundation. The Board of Directors has been very committed to the cause and has been very generous. It’s astounding to me that a set of conversations which began some 24 years ago considering whether we would pay out the first $50,000 in NARSAD Grants has led to a programme that has supported psychiatric research to the tune of close to $300 million and thousands of NARASD Grants around the world. But if you ask, “Are medical researchers adequately funded?” I would say no. We need more resources.

What methods is the Brain & Behavior Research Foundation employing to increase the cooperation between companies, universities, research institutes and other organisations?

One of the things the Brain & Behavior Research Foundation does is foster research at institutions all over the world. So that means that we’ve got many, many countries involved. We try to be as flexible and collaborative as possible in the management-side of the research, to make it as easy as possible for the researchers. It’s not unusual for a researcher to start in one place and end up in some other place, so we facilitate that. We focus heavily on individuals – in the beginning of their careers, in mid-career, and as established investigators – more than on multi-institutional efforts.

What drove you to be the President of the Scientific Council and why do you continue to volunteer your time?

The extraordinary interest that people’s behaviour evokes led me to the field of psychiatry generally, and basically I have been immersed in it. I’ve done virtually every kind of psychiatry – individual psychotherapy, psychoanalysis, hospital, pharmacotherapy, outpatient departments, and adolescent units over the years. I feel deeply troubled by families whose lives are made miserable by these illnesses and I wanted to make it better. I am also extremely fond of the people who have been so generous and good-hearted who form the Board of Directors, staff and management of the Foundation. It’s a wonderful organisation with such an aggressive, positive attitude to try to do something better for people.

Finally, the fact that for years, psychiatric illness was a low priority in comparison with all the other medical illnesses, made me feel that more of us should pitch in and try to do something. All of us, myself included, have had people in our families who have had psychiatric illness and anything we can do to eliminate the likelihood or develop for them better treatments represents a wonderful mission.

www.bbrfoundation.org

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