Scientists have identified the key molecular pathway leading to depression, revealing potential new targets for drug discovery, according to research led by King's College London's Institute of Psychiatry. The study, published today in Neuropsychopharmacology, reveals for the first time that the 'Hedgehog pathway' regulates how stress hormones, usually elevated during depression, reduce the number of brain cells.
Depression affects approximately 1 in 5 people in the UK at some point in their lives. The severity of symptoms can range from feelings of sadness and hopelessness to, in the most severe cases, self-harm or suicide. Treatment for depression involves either medication or talking treatment, or usually a combination of the two.
Recent studies have demonstrated that depression is associated with a reduction in a brain process called 'neurogenesis'- the ability of the brain to produce new brain cells. However, the pathway responsible for this process has, until now, remained unknown.
In this study, Dr Christoph Anacker from King's Institute of Psychiatry and his team studied human stem cells, which are the source of new cells in the human brain, to investigate the effect of stress hormones on brain cell development. 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 and King's College London and the Medical Research Council UK.
Stress hormones, such as cortisol, are generally elevated in stress and depression. The team studied stem cells in a laboratory and found that high concentrations of cortisol damaged these stem cells and reduced the number of newborn brain cells. They discovered that a specific signalling mechanism in the cell, the 'Hedgehog pathway', is responsible for this process. Then, using an animal model, the team confirmed that exposure to stress inhibited this pathway in the brain.
Finally, in order to test the findings, the researchers used a compound called purmorphamine, which is known to stimulate the Hedgehog pathway. They found that by using this drug, they were able to reverse the damaging effects of stress hormones, and normalise the production of new brain cells.
Dr Christoph Anacker, lead author of the study from King's Institute of Psychiatry says: "By decreasing the number of new-born cells in the human brain, stress hormones damage many important brain functions and may contribute to the development of depression after a period of chronic stress. By inhibiting the Hedgehog signalling pathway, stress hormones reduce the development of immature 'stem' cells into mature 'brain' cells."
Dr. Anacker continues: "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. 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."
Anacker, C. et al. 'Glucocoticoid-related molecular signalling pathways regulating hippocampal neurogenesis' Neuropsychopharmacology (2012).
King's College London: http://www.kcl.ac.uk
This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.
Why the connections between brain cells in depressed people are often shrivelled was a mystery – but a single protein could be to blame
The threat of mutually assured destruction, military or economic, promotes peace in many places. If war has ultimately forged a safer world, what's next?
Submarine company says it has recorded detailed images of World War II wrecks off England
Maine baby lobster decline could mean end to record catches as lobstermen, scientists worry
A look at the critters that live on money finds about 3,000 types of bacteria. Most are harmless. But researchers found traces of DNA from anthrax and drug-resistant pathogens, too.
Over its lifetime, Earth has hosted countless species. But some of those species, like the dinosaurs, have managed to claw their way into a special place in our imaginations. Now, a new book illustrates the dinosaurs — and many of the beasts of millennia ago — in beautiful, spectacular and vicious style.
Monkeys have been taught to add, giving the best evidence yet for primates' maths skills and offering a path towards solving how the brain encodes numbers
Comparisons with Neanderthal DNA may point to genes that make us uniquely human and uncover the origins of genetic ailments.
A pair of swans suggests Love Eternal. You often see them in twos, gliding together. But they're not Nature's Coupliest Birds. Which are?
Hundreds of animals trek 240 kilometers across Wyoming