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
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Funding SchemeIP - Integrated Project