World Mental Health Day – interview with two renowned researchers in psychiatry

Every year on 10th of October, the World Health Organization celebrates World Mental Health Day. It is a time to raise awareness on mental health issues and recognize that extensive research programs are still needed to identify, prevent and treat neuropsychiatric disorders. Those include schizophrenia, bipolar disorder, major depressive disorder, and autistic spectrum disorder.

In honor of World Mental Health Day, we invited two world-renowned researchers from our Editorial Board (Professor Sabine Bahn and Professor Sir Robin Murray), to talk about their involvement in the field.

Professor Sabine Bahn is the Director of the Cambridge Centre for Neuropsychiatric Research at Cambridge University, and a Professor for Tranlational Neuroscience at Erasmus University Medical Centre, Rotterdam. Practicing clinician (with an Honorary Consultant position in General Adult Psychiatry at Addenbrookes Hospital, Cambridge), she is also the co-founder of Psynova Neurotech Ltd.

Professor Bahn is a member of the PeerJ Editorial Board covering psychiatry and psychology, translational medicine, and biotechnology .

PJ: What drew you into neuropsychiatric research?

SB: My father suffered from bipolar affective disorder. I guess this was a major factor in the end.

Although initially, when I studied medicine, I wasn’t interested in psychiatry but in neurology, especially epilepsy and my first research papers are in that field.

PJ: Could you tell us a bit about your group and your work?

SB: I have a research group of about 20 scientists and clinician-scientists in my Cambridge lab and a small group in my lab at Erasmus Medical Centre in Rotterdam, NL. I have 3 senior project managers, who help me manage the research and associated administration. Two of my senior project managers held group leader positions in the pharma industry in the past and one is a senior statistician, who supervises the design and statistical analysis of all the work from the group.

My Stanley grant, which is rolling, gives us financial stability to retain key people.

PJ: A few years ago, the Medical Research Council turned down your first major research funding application. Then, you received an extraordinary grant from the Stanley Medical Research Foundation . Could you share some details of this story with us?

SB: The MRC application was right at the beginning of my career about 15 years ago.

They did not like that I wanted to work on post-mortem brain, and they did not like the fact that I was not integrated in a psychiatric department with molecular biological research facilities. It was suggested that I should move to a different university, but I wanted to do my own thing and stayed in Cambridge.

In the end, I “rented” lab space at the Babraham Institute for a few years.

In 2004, I left the Department of Psychiatry in Cambridge and moved into the Institute of Biotechnology, where I was appointed as Professor of Neurotechnology. We have now merged with the Department of Chemical Engineering, and I am the only clinician in the Department and had to adapt to take on examination and supervision of chemical engineering undergraduate students. This was initially a stretch, but now things are working out well.

PJ: You have access to an extensive brain collection via the Stanley Medical Research Foundation. How does it help you to find out more about what causes neuropsychiatric disorders, how to prevent them, and how to treat them?

SB: Right from the beginning of my research into neuropsychiatric disorders, I felt that studying the human brain from patients who died with a diagnosis of mental illness was the best way to approach these complex disorders.

In my view animal models can’t fully or even partially replicate disease processes that affect human thinking and emotions.

The Stanley brain collection has been very important for my research, and we continue to work extensively on these brains. However, we have now also moved into the investigation of peripheral tissues, especially blood serum and blood cells. Several years ago, we found that we can track brain changes by looking in the blood of living patients, and this was a major breakthrough for the group.

As we can’t take out biopsies of brain from living mentally ill patients, as they do in oncology, the potential of using peripheral tissues as a surrogate to investigate central nervous system disease processes is exciting.

Currently, we also develop novel drug discovery approaches on peripheral cells from psychiatric patients.

To come back to the Stanley brains and Stanley Foundation, I can’t express in words my gratitude to Dr Fuller Torrey [Executive Director of the Stanley Medical Research Institute] and Dr Bob Yolken [Director of the Stanley Laboratory of Developmental Neurovirology] as well as the entire Stanley team. For 15 years now, they have stood by me and have supported and believed in my research, which clearly does not fit into the mainstream approaches, and only more recently our line of research has become more widely recognized. However, we are still outsiders in a psychiatric research community that is still looking for “the schizophrenia gene” and “schizophrenia brain image”.

PJ: So, are we getting closer to a cure of schizophrenia and bipolar affective disorder?

SB: I don’t believe we can cure these diseases, but I think that in due course, we can recognize predisposition, and in many cases, prevent the onset of the disease.

For example, we know that the concordance rate for identical twins for schizophrenia is only about 30-50%. Thus, there are almost certainly environmental factors that precipitate the onset of illness. These can often be pinpointed to biological or emotional stress, and frequently can be linked to illicit drug use. If we identify patients at risk and provide intervention in the form of psycho education or low dose medication, this has the potential to reduce conversion into a full-blown psychiatric disorder substantially.

The greatest risk factor is if a patient has already suffered an episode of illness. We need to prevent this first disease presentation, in my view.

PJ: What do you see as the major changes in the field since you started your career?

SB: I definitely think that the biological understanding of the disease has improved, and that we have moved away from only thinking about dopamine receptors.

But, we are still far from the progress made in other fields of clinical science in the quality of research and the translational implications of research findings.

PJ: What are the biggest unanswered questions in the field?

SB: For me it is to define the pathophysiological processes associated with the predisposition and the changes triggering the onset of disease. We need to understand what is happening in that interface, so that we can develop better interventions.

PJ: You do not believe in conforming [Prof. Bahn painted the walls of her lab in pink, her favorite color], and you have a non-traditional approach in research. In your opinion, how do your colleagues perceive it?

SB: I am probably not a conformist, that’s true. We still have the pink lab, which we painted over the weekend when we moved into Biotechnology in 2004. The lab was all grey and dirty, and we just wanted it to look nice, which it does.

I have never really asked anybody what they think about it, and I don’t mind either….

PJ: Can you tell us about any ‘Aha! moments’ in your work?

SB: Well, as outlined above, it was when we were able to confirm abnormalities in pathways related to glucoregulation etc., which we found in post-mortem brain, in cerebrospinal fluid, and blood from first onset drug naïve schizophrenia patients.

We have now also found such changes in first degree relatives of schizophrenia patients, implying that certain glucoregulatory and other alterations are associated with schizophrenia predisposition, and that they affect the whole body, not only the brain.

PJ: In terms of your scientific career, what are you most proud of?

SB: To have developed the first blood test in the field of psychiatry. This test is not perfect yet, but with the help of Myriad Genetics Inc, who bought my university spin-off company Psynova Neurotech Ltd about 2 years ago, we are getting closer to bring a blood test into the market.

PJ: Do you have any advice for researchers who are just starting in the field?

SB: If you have a vision, stick to your own ideas, and take advice only from the right people (there are always lots of people around who want to discourage you).

It’s not easy to find such “mentors”, but I owe a lot to a handful of people who always stuck by me, and I am very grateful to them. I have certainly made enemies on the way as well, not because I wanted to, but because they wanted to hold me back or had other objectives which were not aligned with my ideas…

One has to learn to live with this as well.

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Professor Sir Robin Murray is a Professor of Psychiatric Research at the Institute of Psychiatry, King’s College London, and an Honorary Consultant at the South London and Maudsley NHS Foundation Trust. Past president of the European Psychiatric Association, he is a Fellow of the Royal Society and also a Fellow of the Royal College of Psychiatrists.

Professor Sir Robin Murray is a member of the PeerJ Academic Advisory Board.

PJ: What drew you into psychiatry?

RM: I started reading psychology when I was boarding at an all-boys school. The combination of philosophy and sex in Freud was irresistible to a frustrated adolescent! This led me to study medicine with the aim of doing psychiatry, and I have never regretted it for a second.

PJ: Could you tell us a bit about your group and your work?

RM: I have worked for many years as part of the psychosis group at the Institute of Psychiatry, which is the largest outside the USA. This has allowed us to approach the pathogenesis of schizophrenia and other psychoses from a broad perspective, and using a range of techniques from epidemiology and psychology, through genetics to imaging, pharmacology, and molecular biology. So although our fundamental research is not as good as that of others, our research at the interface between different disciplines is better.

PJ: What influences have shaped your research?

RM: Working with colleagues cleverer than me.

PJ: Your list of hot-papers includes results on auditory hallucinations of patients with schizophrenia ( Shergill et al., 2000 ). Could you share some details about this work?

RM: Our group, led by Phil McGuire and Suhki Shergill, was the first to find imaging evidence for Chris Frith’s hypothesis that auditory hallucinations are often due to a misinterpretation of inner speech. The internal words, or thoughts, are produced in the normal way by Broca’s area but somehow the auditory processing areas fail to recognize that the words are self-generated and process them as if they were coming from outside. In this way the brain is tricked into regarding the internal words as external voices.

PJ: Among your most-cited papers are two that investigate the link between genetics and psychotic disorders in twins ( Cardno et al., 1999 ; Cardno et al., 2003 ). In your opinion, why did the articles make such an impact?

RM: Firstly, the well co-twin of an identical twin with schizophrenia is an ideal subject to compare with the sick twin; this has helped to elucidate which aspects of schizophrenia are inherited (and shared by both twins), and which result from the illness or some factor related to it (and thus found only in the sick twin). Secondly, Alastair Cardno was able to use the Maudsley Twin Register to show that when one identical twin had schizophrenia, the second was also so in 42% of cases, but a further 10% had qualified for a diagnosis of mania; conversely when one twin had mania, the second also did in 36% of cases, but another 8% qualified for a diagnosis of schizophrenia. If the two conditions were genetically totally distinct, this shouldn’t happen. Lots of psychiatrists wedded to the traditional diagnostic systems were very antagonistic to this idea but now other clinical and molecular studies have demonstrated that we were correct.

PJ: Your group’s papers also include striking results on obstetric complications as a risk factor for the later development of schizophrenia ( Cannon et al., 2002 ). How did you become interested in this?

RM: I was persuaded that schizophrenia might be partly neurodevelopmental by one of my then junior colleagues, Dr (now Professor) Shon Lewis, who identified brain abnormalities in the scans of people with psychosis, which could only have originated in utero. So we hypothesized that people with schizophrenia should show an excess of developmental insults and so it proved with obstetric events. So we proposed the neurodevelopmental hypothesis of schizophrenia in 1987, almost at the same time as Dan Weinberger in the USA. To my surprise this theory rapidly became accepted and indeed now I think is over-accepted. I don’t think schizophrenia is a just a neurodevelopmental condition; rather there are neurodevelopmental risk factors for its onset but there are other risk factors including certain types of social adversity.

PJ: Your investigations on cannabis and schizophrenia have also attracted a huge amount of interest ( Arseneault et al., 2004 ). Could you comment on this?

RM: In the first decade of this century several groups in Holland (especially Jim Van Os) and in the UK became interested in why so many people with schizophrenia smoked cannabis. In retrospect, I think this arose because cannabis had started to become much stronger in these two countries. We and other groups were able to show that the cannabis consumption started long before the onset of psychosis and that the more frequently one smoked and the greater the potency of the cannabis used, the greater was the risk; of course only a small minority of cannabis users ever have problems, so presumably the individuals who react adversely carry some genetic susceptibility.

PJ: What do you see as the major changes in the field since you started your career?

RM: In Europe (though not yet in the USA) the bitter old arguments about biological versus social factors have gone. Now most researchers and clinicians regard schizophrenia as multifactorial with multiple genes interacting with a range of environmental risk factors.

PJ: Are we getting closer to a scientific understanding of schizophrenia?

RM: Certainly, but in the process of doing this, we are realizing that schizophrenia is not a discrete disease entity; rather it’s an umbrella term for a clinical syndrome, which probably results from a range of different causes (just like anemia or learning disability).

PJ: What are the next big questions, and where would you like to see the field go from here?

RM: I am most interested in gene-environmental interaction. Will a general genetic loading make the same individual susceptible to a range of different environmental factors, or will different combinations of genes interact separately with different environmental factors? I suspect the latter.

PJ: In terms of your scientific career, what are you most proud of?

RM: Having been able to spot and train lots of very bright young researchers who have gone on to do brilliant work elsewhere (and to remain friendly with me).

PJ: Do you have any advice for researchers who are in the field?

RM: Firstly, don’t follow the herd into the popular technique of the day but develop an expertise that nobody else has; then collaborate with the best of the rest.

Secondly, when you have a novel idea you may find that some senior figures may be quite hostile. Stick to your guns and when ten years later, they claim that they were among the first to develop the idea, just smile and congratulate them on their foresight!

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We would like to thank Prof Sabine Bahn and Prof Sir Robin Murray for participating in this post and we encourage you to support World Mental Health Day. Click here to read PeerJ articles in the areas of psychiatry and psychology