Göran Sedvall

Göran Sedvall who is Professor Emiritus of Psychiatry at the Karolinska Institutet and former head of the Psychiatric Clinic of the Karolinska Hospital, was born in Stockholm, Sweden in 1936. Dr Sedvall has spent most of his scientific life at Karolinska Institutet in Stockholm. When arriving at the Karolinska as a medical student in 1955, he was encountered by a number of important developments and personalities in the field of brain research. Ulf von Euler had recently identified noradrenalin as the important sympathetic transmitter and also shown that it is present in the brain. New drugs as reserpin and chlorpromazine had been shown for the first time to affect the life of patients with the delusive psychotic disorders. Arvid Carlsson and Nils - Åke Hillarp had made the fundamental discoveries that these drugs have profound effects on storage mechanisms for neurotransmitter amines and also unequivocally visualized that not only noradrenalin but also dopamine and serotonin are localized to specific signalling neuronal systems in the brain. These were all highly inspiring events and a challenging environment for the young medical student, who joined the Department of Pharmacology under Professor Börje Uvnäs in 1958 as a Ph.D. student. In parallel with finishing his thesis (see picture of thesis frontpage) - an experimental study on reserpin effects on transmitter release from sympathetic nerves in the cat - he completed his medical studies in 1965.

The Period at the National Institute of Mental Health
For a young Swedish medical doctor at that time, the National Institute of Mental Health (click on logo to get to the Karolinska Institutet homepage) in Bethesda, Maryland, was a Mecca for methodological developments in brain research. In 1965 he was offered a postdoctoral position in Irwin Kopin's Lab and opportunities to learn the importance of method development and how to organize interaction between basic and clinical research. The scientific environment at that time included highly creative scientists from different fields as Julius Axelrod, Seymour Kety and Sidney Udenfriend to name only a few. With Irwing Kopin radiotracer methods to examine neurotransmitter synthesis in sympathetic nerves in living animals were developed. With these methods he demonstrated how impulse activity in such nerves profoundly accelerates neurotransmitter synthesis. He also examined cetecholamine synthesis in the brain and demonstrated that chlorpromazine and other antipsychotic drugs had dramatic and selective effects on dopamine synthesis in the brain, a discovery that focused interest on the role of dopamine in contrast to the other transmitter amines as a mediator of the antipsychotic action of neuroleptics.

Returning to the Karolinska Institutet
After returning to Sweden in 1966 he completed his specialist training in psychiatry and subsequently became the first Swedish professor of neuropsychopharmacology at the Karolinska Institutet (click on logo to get to the KI homepage) in Stockholm in 1971. Fundamentally interested in the biological nature of psychotic phenomena he became increasingly motivated to transfer knowledge based on animal experimentation into the clinical field. Eager to explore monoaminergic mechanisms in the brain of psychotic patients he participated in the development of masspectrometric methods for measuring monoamine metabolites in the cerebrospinal fluid (CSF). Using these methods in experimental psychiatric research together with his students, he demonstrated high variability in monoamine metabolite concentrations in the CSF of psychotic patients and also, on the basis of systematic clinical dose response studies profound effects of different types of neuroleptic treatments on dopamine metabolite concentrations in the CSF and relationships to clinical response and prolactin elevation.

PET Development
On the basis of these scientific contributions Göran Sedvall was elected to the prestigious chair of psychiatry at the Karolinska Institutet and Hospital in Stockholm in 1980, a position he is still maintaining. As the new professor of psychiatry at the Karolinska Institutet he was happy to be approached by Swedish pioneers in developing PET technology for brain research, Torgny Greitz and Lennart Widén. With his background in vivo radiotracer work there was an obvious potential to examine radioligand binding to neuroreceptors in the living human brain (see figure, click för larger image). This possibility was based particularly on the important in vitro work performed by Phil Seeman in Toronto, Canada, and pioneered by Henry Wagner and Dean Wong at John Hopkins University, Baltimore, Maryland, US.

Collaboration with Astra
Being intrigued by the high selectivity of sulpirid, a substituted benzamide, for D2 dopamine receptors he approached Sven - Ove Ögren and Håkan Hall at the Swedish Astra Company who had participated in the development of a series of substituted benzamides as potential antipsychotic agents. Raclopride was selected as the ligand of choice for probing D2 dopamine receptors in the living human brain. 11C - Raclopride and other radioligands were soon developed in collaboration with skilled radio chemists and a series of clinical PETstudies were initiated in collaboration with several of his MD, PhD students. Among those Lars Farde was creative and energetic in refining methods for quantification of receptor binding variables and in finding new applications of this technique which has now been one of the main stay tools for early characterization of central neuroreceptor binding drug candidates. These methods have allowed the visualization of distributions and binding characteristics of several monoaminergic neuroreceptors in the brain of patients with neuropsychiatric disorders as well as allowing in vivo quantification of receptor occupancy in relation to pharmacological treatment of human subjects.

A second round in the US
To approach new developments in molecular neuroscience Dr Sedvall spent another stimulating year (sabbatical) in the US in 1985 - this time in Paul Greengards Lab at Rockefeller University in New York, New York, US.

Back in Sweden again
Coming back to Sweden and the Karolinska Hospital (see photo of entrance to the psychiatric clinic) in 1986 new projects were initiated aiming at further exploring the biochemical anatomy of the human post mortem brain with important contributions from Håkan Hall and Yasmin Hurd. With the accumulation of overwhelming evidence for a multifactorial etiology of schizophrenia, the reductionistic experimental approach to these disorder characterising Göran Sedvalls previous work seemed insufficient to spread new light on the interplay between genetic and environmental influences behind vulnerability for schizophrenia. Particularly the methodological achievements in molecular genetics and clinical data accumulated so far underline this view. For such reasons Dr Sedvalls scientific ambitions during the past decade have moved to an interdisciplinary integrative approach.

Human Brain Informatics and its Database
With the support of Swedish and international research funds Dr Sedvall and his collaborators are now engaged in developing an optimized clinical research organization focusing on the etiology and pathophysiology of schizophrenia. This research organization named the "Human Brain Informatics" project (HUBIN) aims at comparing defined Swedish populations of schizophrenia patients and control subjects with regard to molecular genetic, early environmental influences, brain imaging and neuropsychological data as well as data for detailed phenotypic neuropsychiatric characterization. Data from these projects are entered into a major clinical relational database (HUBIN database) which will be successively developed during the first decade of this century. This database is expected to become an appropriate tool for multivariate and data mining statistical exercises to explore complex interactions between genetics and environmental factors on one hand and on the other hand brain development and characteristics in causing minor alterations of brain organization with psychopathological signs and symptoms differentiating the schizophrenia patient population from non psychotic control subjects. This database will hopefully become an important research tool in itself, it will also be useful as a reference for validation of research findings appearing from other studies in the field.

Göran Sedvall's Involvement
Göran Sedvall has served on the council of the CINP (Collegium Internationale Neuropsychofarmacologicum) since 1998. He was chairman of the Awards committee of the CINP 1995, the Budget and Finance Committee in 1996 and was elected to one of the two vice president positions of the CINP in 1998. Göran Sedvall is president elect of AEP (the Association of European Psychiatrists) since 1999, and he is currently one of three Managing editors for European Archives of Psychiatry and Clinical Neuroscience.

In the Spare Time
Somehow integrated with these scientific interests Göran Sedvall has a great ambition to find time for his family, wife Marie, five children and seven grandchildren. With them he enjoys sports like tennis and sailing as well as the love for nature including gardening, hunting and forestry in the countryside home south of Stockholm.

Göran Sedvall's biography

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