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New molecules in mood disorders: a genomic, neurobiological and systems approach in animal models and human disorder

Objective

Depression is common and affects twice as many women as men. In the global burden of disease survey, it is the fourth most prevalent cause of disability, greater than eg cardiovascular disease. Gender, social and familial factors increase risk for depression, but little is known about how these influences work in the brain, least of all at the molecular level. Newer antidepressant treatments still act in the same way as 30 years ago and their downstream molecular actions are obscure. At most 65% of new episodes respond to drug-treatment and chronic, treatment-resistant depression is a major health burden.
This is a major collaboration between 13 clinical and basic science groups in 10 EU countries which
addresses the evident need to discover:
New molecular mechanisms in the causation of depression.
New molecular mechanisms of effective drug-treatment.
We will measure three fundamental processes underlying depression - the inability to experience pleasure, excessive sensitivity to stress and negative appraisal of circumstances. This will enable us to cross-validate findings, in humans and animal models. In animals we will use a mixture of well-established and novel methods for inducing genetic and mild stress-related changes in the three processes. We will detect the molecular mechanisms involved by creating the NEWMOOD microarray chip and measuring changes in gene expression. Changes which are consistent across many models will become targets for new treatments. In addition we will search for neurochemical changes in how monoamine and other neurones are regulated which are shared by the models. These too will become new molecular targets.
Humans with varying genetic and environmental risk factors will be compared on the three behaviours and on the brain systems and neurotransmitters responsible using functional magnetic resonance imaging.

Call for proposal

FP6-2002-LIFESCIHEALTH
See other projects for this call

Funding Scheme

IP - Integrated Project

Coordinator

THE UNIVERSITY OF MANCHESTER
Address
Oxford Road
Manchester
United Kingdom

Participants (13)

INSTITUT NATIONAL DE LA SANTE ET DE LA RECHERCHE MEDICALE
France
Address
Rue De Tolbiac 101
Paris
UNIVERSITY OF WUERZBURG
Germany
Address
Sanderring 2
Wuerzburg
UNIVERSITAT POMPEU FABRA
Spain
Address
C/dr Aiguader 80
Barcelona
UNIVERSITY OF TARTU
Estonia
Address
Ülikooli18
Tartu
UNIVERSITY OF MAASTRICHT
Netherlands
Address
Universiteitssingel 50
616 Maastricht
NATIONAL INSTITUTE OF PSYCHIATRY AND NEUROLOGY
Hungary
Address
Huvosvolgyi Ut 116
Budapest
THE UNIVERSITY OF EDINBURGH
United Kingdom
Address
Old College, South Bridge
Edinburgh
CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD
United Kingdom
Address
University Offices, Wellington Square
Oxford
KAROLINSKA INSTITUTET
Sweden
Address
Retzius Väg 8
Stockholm
UNIVERSITÀ DEGLI STUDI DI FIRENZE, DIPARTIMENTO DI FARMACOLOGIA PRECLINICA E CLINICA
Italy
Address
Piazza San Marco 4
Firenze
UNIVERSITY OF NAVARRA
Spain
Address
Pamplona
177 Navarra
INSTITUTE OF GENETICS & ANIMAL BREEDING OF THE POLISH ACADEMY OF SCIENCES
Poland
Address
Jastrzebiec, Postepu 1
Wolka Kosowska
SEMMELWEIS EGYETEM
Hungary
Address
Üllöi Út 26
Budapest