The Dr Paul Janssen Award for
Pharmacology was founded in 1998 by Janssen Pharmaceutica.
This biennial award is presented in recognition
of an individual’s outstanding contribution
to scientific research related to fundamental
or clinical knowledge in the field of pharmacology.
The area of pharmacological research for which
the award is made is variable; for the period
2002-2003 it was related to psychopharmacology.
The award carries a cash prize of € 25,000.
The Royal Academy of Medicine of Belgium, which
evaluates the entries for the award, has bestowed
the Dr Paul Janssen Award 2002-2003 on Prof. Ronald
Stanton Duman for his work entitled ‘A neurotrophic
hypothesis of the pathophysiology and treatment
of mood disorders’. The award will be presented
on Wednesday, December 3, 2003 in Brussels, at
a ceremonial sitting in the Royal Academies of
Science and the Arts of Belgium.
Prof. Duman was born on February 6, 1954 in Colver,
Pennsylvania, USA. In 1976 he earned his Bachelor
of Science degree from the William and Mary College
in Williamsburg, Virginia. From 1977 to 1980 he
worked in the Biology Laboratory at the University
of Notre Dame in South Bend, Indianapolis. From
1980 to 1986 he was on the staff of the University
of Texas Medical School in Houston where he gained
his doctorate in 1984. Since 1986 he has been
attached to the Laboratory of Molecular Psychiatry
of the Departments of Psychiatry and Pharmacology
at the Yale University School of Medicine in Connecticut.
He is currently Professor of Psychiatry and Pharmacology
and Director of the Molecular Psychiatry Division
and the Abraham Ribicoff Research Facilities.
The research of Prof. Duman is situated in the
field of depressions and the treatment of these
conditions. Antidepressants have been on the market
for more than 40 years and are widely prescribed.
Nevertheless their exact mechanism of action is
still poorly understood. While most antidepressants
immediately block the resorption or metabolism
of serotonin and/or noradrenaline in the brain,
there is a time lag of several weeks between starting
treatment and the point when clinical improvement
of the depression becomes visible.
This has led to the perception that cellular
changes to the higher concentrations of serotonin
and noradrenaline are required for the therapeutic
effect. Prof. Duman has devoted his entire career
to the study of these cellular effects. In his
research, which spanned more than two decades,
he unraveled the mystery of how antidepressants
produce their effect on the signal transduction
paths in neurons, including the regulation of
gene expression.
Prof. Duman’s studies have resulted in
a major new concept in research into depression
and the treatment of depression, which is described
by him as a neurotrophic hypothesis of depression.
Prof. Duman's studies demonstrated that chronic
administration of different classes of antidepressants
increased the expression of cAMP response element
binding protein (CREB) in limbic parts of the
brain, including the hippocampus. The hyperexpression
of CREB in the hippocampus of experimental animals
caused the depression in two animal models of
depression to disappear in the same way as by
giving antidepressants, which he regarded as proof
that CREB is indeed a key molecule in the mechanism
of action of antidepressants. Since CREB is a
transcription factor, he then went in search of
target genes and he identified the Brain Derived
Neurotrophic Factor (BDNF). Chronic administration
of antidepressants increased the expression of
BDNF in the hippocampus, and the infusion of BDNF
in certain parts of the hippocampus in experimental
animals caused the depression to disappear. He
was able to confirm these changed expression levels
of CREB and BDNF in autopsies on patients who
had been treated with antidepressants.
These findings spurred Prof. Duman to study the
growth of axons in the brain. Antidepressants,
with CREB and BDNF as mediators, stimulated the
growth of new axons in the hippocampus and increased
the survival of these neurons. These effects did
not occur after acute antidepressive treatment
but they were manifested after chronic treatment,
which corresponds to the weeks or months that
are required before clinical improvement becomes
apparent with antidepressants. These findings
are relevant because the axons and the surrounding
glia cells in the limbic system of depressive
patients suffer atrophy and may even die, causing
the hippocampus to become smaller radiologically.
This loss of axons can be counteracted by chronic
administration of antidepressants because they
stimulate the regeneration of lost neurons and
thus stop and even reverse further atrophy of
the limbic system.
From the entries submitted for the Dr. Paul Janssen
Award, the members of the jury chose the work
of Prof. Duman because his studies have led to
new insights into the physiopathology of depression
and because new mechanisms of action of antidepressants
have been clarified. The jury praised the arsenal
of advanced, state-of-the-art technology that
was used, ranging from behavioral studies in animals
to the creation of transgenic animals, viral-mediated
hyperexpression studies in animal brains and postmortem
studies of the brains of deceased patients. The
jury also set high value on the perspectives that
his work opens up for the development of new generations
of antidepressants, for instance via the direct
activation of CREB by increasing the intracellular
concentration of cyclic AMP. These cutting-edge
research findings have been published in leading
scientific journals, including Nature, Science,
Neuron and Archives of General Psychiatry. Moreover,
his work is widely quoted by his colleagues.
For all these reasons, the jury has unanimously
decided to bestow the Dr Paul Janssen Award 2002-2003
on Prof. Ronald Stanton Duman, Professor of Psychiatry
and Pharmacology at the Yale University School
of Medicine in the United States of America.
For more information:
Royal Academy of Medicine of Belgium
Prof. Marc Bogaert
Tel.: 02.550.23.00
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