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.
With funding from the Defense Department, scientists have begun work on devices that would use electric pulses to realign a memory process gone awry
On Friday, the Food and Drug Administration released a vital set of numbers about the routine use of antibiotics …
Side order of veg with that mammoth leg? The Neanderthal diet was probably more varied than we think – using vegetables, herbs and different cooking techniques
An exoskeleton that enables movement and provides tactile feedback has helped eight paralysed people regain sensation and move previously paralysed muscles
A female western gray whale set a new record swimming from Russia to Mexico and back, a total of 13,988 miles, in 172 days
Scientists operating a remote-controlled vehicle about 2,000 feet below water get a rare glimpse of a sperm whale. CBSN's Vladimir Duthiers and Elaine Quijano report on the video.
According to the experts, "blinking is like a kitty kiss"
Genetic profiling of cancer cells can help guide treatment, but such profiles can be ambiguous. Results would be more accurate if all labs tested normal cells from each patient, too.
Researchers in Kenya uncover tools dated to 3.3 million years ago, long before the first humans, as we know them, walked the Earth.
Researchers are facing up to methodological flaws that plague functional magnetic resonance imaging, but the interpretative problems might be harder to solve