Scientists at King’s College London’s Institute of Psychiatry believe they have identified the key molecular pathway leading to depression, opening up the potential for new drug discoveries.
The study revealed that the ‘Hedgehog pathway’ regulates how stress hormones, which are usually elevated during periods of depression, reduce the number of brain cells.
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The research, which was published yesterday in Neuropsycopharmacology, is linked to recent research that revealed depression is associated with a reduction in brain processes called ‘neurogenesis’, which is the ability of the brain to produce new brain cells.
Before now the pathway responsible for this process was unknown.
This new research could lead to new drug discovery for depression, a condition that currently affects 1 in 5 people in the UK at some point in their lives and is usually treated with medication, talking therapies, or both.
Lead author of the study from King’s Institute of Psychiatry, Dr Christoph Anacker, said; "With as much as half of all depressed patients failing to improve with currently available treatments, developing new, more effective antidepressants still remains a great challenge, which makes it crucial to identify new potential mechanisms to target.
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By GlobalData"The discovery of antidepressants has so far been mainly by serendipity. Developing a drug with a defined effect on the brain, such as increasing the number of new-born brain cells, and with a clear target, such as Hedgehog signalling, will allow us to develop much more specific antidepressants in the future."
During the study, Anacker and his team studied human stem cells – a source of new cells in the human brain – to investigate the effect of stress hormones on brain cell development.
They discovered that high concentrations of stress hormones, such as cortisol, damaged these stem cells, reducing the number of newborn brain cells and that a specific signaling mechanism in the cell, the ‘Hedgehog pathway’, is responsible for this process.
Using an animal model they confirmed that exposure to stress inhibited this pathway in the brain.
They then used a drug called purmorphamine – know to stimulate the Hedgehog pathway – and found the use of this drug reversed the damaging effects of stress hormones, normalising the production of new brain cells.
The study was funded by the National Institute for Health Research Biomedical Research Centre for Mental Health at the South London and Maudsley NHS Foundation Trust, King’s College London and the Medical Research Council UK, with additional funding from a Commission of European Communities 7th Framework Programme Collaborative Project Grant, a NARSAD Young Investigator Award, Research Councils UK, Italian Ministry of Health, Regione Lombardia and the Italian Ministry of Health.
Image: Depression affects 1 in 5 people in the UK at some point in their life. Photo: Courtesy of Christer Rønning Austad.
