Prof. Dr. Andreas Meyer-Lindenberg
Director oh the Central Institute for Mental Health (ZI), Mannheim
Interview of October 6, 2008 with Dr. Birgit Teichmann
The realization that biological mechanisms are responsible for the development of psychiatric symptoms had a break-through in the middle of the Seventies. At the latest in the Nineties, when the “Human Genome Project” was started with the goal to identify all human genes, the question arose to what extent human behaviour is genetically pre- determined. 70% of all genes are expressed in the brain and have some influence on cell functions and eventually on the development and functions of complex brain systems.
Is the human being, with regard to behaviour, a slave of the genes?
Certainly not, the genetic portion, i.e. the hereditary part, lies between 20, 40 or maybe 50%, which, however, doesn’t mean that any single gene or combination of genes is known to substantially determine our behaviour. Nevertheless it is interesting to see how genes may be involved in controlling behaviour, not because they are the decisive criteria, but because this may be an approach to find out what from a biological point of view is underlying certain ways to behave.
What influence does environment have?
We estimate that social behaviour is determined almost equally by environmental influences as by the part of the genes themselves and that genes and environment are not acting by themselves but interact with each other. There are certain genes which increase the risk to react with depression or fear when a certain environmental stress is involved. These gene-environment interactions are most probably responsible for a complex entwinement of causes underlying each individual way to behave.
Is it possible to carry a certain gene “making aggressive” and still lead an inconspicuous life?
Yes, of course. These genes, which we have studied intensively, each of them account for only a very minimal part of aggressive behaviour and therefore it doesn’t make sense to measure them individually. We have been asked this question quite often in connection with people considered for death sentence. Because they contribute that little bit to the predisposition to react aggressively, we have a chance by investigating into these genes to learn more about aggression, even if not in the individual case.
You have discovered that genes not only influence metabolism in the brain and the irritability of neurons. Their influence also changes the structure of those brain cells that are involved in the control of human social behaviour and emotional life. How can we envision this?
There are control circuits in the brain which regulate e.g. basal emotions or the level of attention. They are essentially not under our control, but they play an important role in how we feel and how we react to environmental influences. We have found that genes also play an important part in how these control circuits, especially in handling basal emotions, are connected, namely that genes which increase the risk to become depressive or aggressive, or to show fear reactions disturb the functions of the control circuit. It is less strongly connected, which by itself may have little or no impact, but if an environmental stress factor is added then the whole system may compensate and the person may react in the form of a disease.
What does “imaging genetics” mean?
With this approach we try to establish a connection between genes and brain function. A large group of people are examined to determine their genetic variants, then brain function is measured e.g. by means of functional magnetic resonance imaging, which can be done here at the Central Institute or also at the University of Heidelberg, and maybe brain structure is measured as well. We can thus determine the size of the brain and of the different brain structures. Then we can look at the connection between genetic variant and size of brain regions we are interested in, their activity, or the way these brain regions are interconnected.
What influence do these new methods have on diagnosis and therapy?
Their influence is still quite limited, but this will no doubt change over the next years, because using this imaging genetics approach we discover brain systems that have to do with genetic risk, and there is already first evidence that it has preventive value, for instance to predict who might respond to a given antidepressive or not, or who might profit from a certain therapy or not. The genes themselves do not actually explain to which extent each single one of them is contributing to a special way to behave. Nevertheless, we have been able to identify brain mechanisms through these techniques that have clearly improved our understanding of the variability in this interesting field so that we can in fact say who will improve when given a certain antidepressive.
Quite a lot of things are conceivable. The actual use of such a gene therapy that would intervene in the human inheritance is still far away. But we are very interested to watch how a genetic variation shows in the course of time, especially in childhood, and although the gene itself cannot be replaced, with our knowledge of the mechanisms involved we can think about training other brain regions that are functioning well in order to strengthen their function. The plasticity of the brain is a great asset, and it may recover to a certain extent from all disorders of early youth, especially if the right therapy and training methods are available.
Don´t we need – in spite of all this –the abnormal, the deviant to make our world more interesting? Without their deviant behaviour many artist might not have created the work they were able to produce with their disease. The Prinzhorn Collection may be a good example for this fact.
Of course we need variation in human life, and I do not want to pathologize behavorial apects that I investigate. In other words, the fact that a genetic variant is connected with a behaviour does not make it abnormal or a disorder, by no means. A great number of traits we investigate, for instance being more or less fearful or more or less aggressive, are all within the range of normality. Our behaviour and what we classify in a certain context as pathological or not pathological, all this exists within the same network of human relations. Therefore I think by extending our knowledge and understanding we should be able to stop the stigmatization of mental disorders in our society and I would regret it very much if it would turn out to be the opposite
Personal Data
Andreas Meyer-Lindenberg was born in 1965 in Bad Godesberg. He studied medicine in Bonn. His scientific schooling took place in Bonn, New York and at the National Institute of Mental Health, Bethdesda. Since July 2007 he is director of the Central Institute of Mental Health, Mannheim.
His scientific focal point is the research of schizophrenia and depression by magnetic resonance imaging, genetical and psychopharmalogical methods as well as the testing of biological mechanism of human social behaviour.
Andreas Meyer-Lindenberg is married and has two children. He is a big opera fan and in his leisure time you will meet him in the opera houses of Mannheim and Stuttgart.
