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28 novembre, 2012 - 20:39

We've heard you talk about risk factors in Schizophrenia. Where do you think we are at in research into risk factors of Schizophrenia and what do you think future research into risk factors should focus on?
It's becoming very much big epidemiological samples research, and meta-analysis, even though people have different views of whether meta-analysis are good. I don't like them very much myself. I think they tend to include even bad studies, and some of the results are watered down. If you enter messy data into them then it clearly has an impact on odds ratios. 
This is a time for epidemiological research and I do epidemiology myself. I think probably a multiple approach, looking at relationship between risk factors and the brain would be the most relevant. 
The question of brain, risk factors and symptoms is important, but symptoms often get lost. On the other hand, there has been such a dominance of molecular genetic studies that don't add much knowledge. 
There seem to be so many risk factors involved, which also seem to vary from centre to centre and country to country and I think you bring a certain amount of “damnation” on yourself for having such high expectations on certain risk factors. By and large the field is very dynamic, but you have to have a certain tolerance of ambiguity, you have to be a detective really, if you want to deal with risk factors.

You talked about early and late risk factors, how easy do you think it will be to disentagle the role of those and other factors in the development of the disorder?
I think one of the big challenges in the next few years will be the reappreciation of social risk factors, that were out of fashion for many years and then some studies started looking at them, also thanks to Robin Murray and his studies. The whole idea of childhood is also becoming very relevant, thanks to British studies, showing that childhood is important and it is not only pregnancy or birth that have an impact on becoming schizophrenic

How easy do you think it will be in the nearest future to have a real model of the aetiology of schizophrenia?
Models are always done, models is the only thing we researchers do. The important thing is being able to test them, not only believing in them. 
Schizophrenia research is a field where hypotheses came all the time, and they were never disproved, they grew old and died. Some people believe that if you disprove a theory it's a failure and actually I think that's what science is about, disproving theories. Science should do something about disproving what people believe. However, scientists seem to prefear things that are invisible. If someone said that the lenght of the little finger accounts for 15% of the variance in schizophrenia, they would't like it, because it's too obvious.

Clearly in all of this you often loose touch with patients and clinical reality, as you said in one of your last slides
Yes and I think Prof. Maneros idea that one ought to distinguish between syndromes is very important and it has to do with the question of specificity. Maybe it's that if you can't tell a person with schizophrenia from one with Bipolar disorder then you won't find any difference in causing factors for those two diseases and that might be very true. On the other hand what bothers me is finding so many different risk factors for one and the same disease. Not getting too specific about diagnosis is a question of convenience, it is hard enough to scrape together 35 cases exposed to rubella, imagine if you have different groups: schizophrenia, schizoaffective and affective disorders and a few atypical psychosis cases. You do it, because that's the way you have to do research. I don't know of any large sample that have shown major risk factors differences amongst subgroups of patients. It's also that there are different ways of definying diseases one is the usual way according to symptoms, the second is by course and outcome, the third will be by aetiology and the fourth is treatment and response to drugs. However, the tradition in psychiatry is as Prof. Marneros mentioned, to distinguish by symptomatic presentation.

The idea of that split between categorical and dimensional diagnosis is something that is very relevant to clinical practice, but difficult to apply.
Yes that is a very relevant issue and the question is: these disorders are a continuum of what? If it's of symptoms then yes I buy it, if it is a continuum of aetiology I don't know, because we don't know what the aetiology is of these disorders. If it is a continuum of biological, neuropsychological and neural disorder, then I don't buy it. 
In one of our study we showed that there is a huge difference between offsprings of women with schizophrenia and affective disorders, in that if you study neurology throghout their life, from prebirth up to 22 years of age, it's two groups of individuals at risk completely different from each other. On some dimensions offsprings of women with affective disorders are better than controls on cognitive functioning and neurological abnormalities, so if that's true how can you say that these diseases are on the same neurobiological continuum, they are very very different. I think it is very important to remember what one is talking about to avoid generalisations.

How does this all fit into the research you are currently doing in your department?
We do most of this but not all of this. We' ve done a lot of the obstetric complications research. But I think hopefully research makes progress, we started doing obstetric complication research in the late 70s and it wasn't generally accepted that obstetric complications were risk factors for schizophrenia. This was replaced by epidemiological research. The question is to try and make progress regarding what's needed and valuable at one particular point in time. I mean, if there are 21 studies on the epidemic of influenza of 1957, we don't need the 22nd, unless you' ve got a very good idea of what is wrong with the first 21. Someone at the last schizophrenia meeting at the Maudsley said we should all stop doing research for 6 months and think!

The last question I wanted to ask is about Europe and there were talks today about how to integrate psychiatric research and practice onto a european platform. How do you think that can be best done in the nearest future?
In practice I really don't know regarding research and funding from the EC, this has become extremely bureacratic, I don't have much experience. Cross-national studies are very valuable and mainly from an epidemiological point of view and the range of factors you can look at. Practically there is a difficulty with language and using the same diagnostic instruments, but putting researchers together to collaborate is not the easiest of things.

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