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FP6

NEWMOOD — Result In Brief

Project ID: 503474
Funded under: FP6-LIFESCIHEALTH

A new mood to escape depression

New knowledge of the molecular basis for depression is laying the foundation for new drugs to combat mood disorders. Recent EU research has investigated genes whose expression products are triggers for depression.
A new mood to escape depression
Depression represents a significant source of reduction of life quality. Fourth in the league table as a cause of disability, treatment-resistant depression exacts a high cost socially and economically.

Three fundamental processes in humans underpin mood disorders – inability to experience pleasure, excessive sensitivity to stress and negative appraisal of circumstances. Although gender, social and familial factors also contribute to predisposition to depression, little is known about how these factors translate into molecular mechanisms in the brain.

With the objective of identifying new molecules involved in mood disorders, the 'New molecules in mood disorders: a genomic, neurobiological and systems approach in animal models and human disorder' (Newmood) project designed gene expression studies.

Newmood researchers took a genomic approach aiming to identify and confirm genes that changed in terms of expression in animal models with a vulnerability to depression. Gene candidates were then confirmed in humans by association with markers for vulnerability. Another follow-up approach came from expression studies in post-mortem of patients with depression.

The first step was to create genetically modified mouse models to test for translational changes with prompts for depression, including maternal separation and chronic mild stress. Combining translational studies with the Newmood expression array data offered a means of rapid validation of the new candidate genes.

Newmood has developed a comprehensive translational dataset for rodents and humans for gene expression data linked to the pathogenesis of depression. The data associates molecular activity to carefully validated behaviour markers occurring as a result of brain activity.

The researchers found that several genes affect vulnerability in rodents and humans through similar processes. These include the CB1 cannabis receptor, the 5-HT transporter, tryptophan hydroxylase 2 and brain-derived neurotrophic factor (BDNF). Newmood believe that they will be able to devise a new hypothesis-testing method to detect depression-linked molecular mechanisms.

Project results have laid the foundations for a molecular picture of mood disorders. Discovery of genes whose activity varies with depression is the first step in a new research pathway that promises to identify novel drug targets and new pharma products for depression.

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