Discovery of pathway leading to depression reveals new drug targets

December 6, 2012

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.

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 process called 'neurogenesis'- the ability of the brain to produce new . 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 , which are the source of new cells in the , to investigate the effect of 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 . 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."

Explore further: New target for developing effective anti-depressants

More information: Anacker, C. et al. 'Glucocoticoid-related molecular signalling pathways regulating hippocampal neurogenesis' Neuropsychopharmacology (2012).

Related Stories

New target for developing effective anti-depressants

April 12, 2011

For the first time in a human model, scientists have discovered how anti-depressants make new brain cells. This means that researchers can now develop better and more efficient drugs to combat depression.

Tripping the switches on brain growth to treat depression

August 15, 2012

Depression takes a substantial toll on brain health. Brain imaging and post-mortem studies provide evidence that the wealth of connections in the brain are reduced in individuals with depression, with the result of impaired ...

Recommended for you

Can physical exercise enhance long-term memory?

November 25, 2015

Exercise can enhance the development of new brain cells in the adult brain, a process called adult neurogenesis. These newborn brain cells play an important role in learning and memory. A new study has determined that mice ...

New insights on how cocaine changes the brain

November 25, 2015

The burst of energy and hyperactivity that comes with a cocaine high is a rather accurate reflection of what's going on in the brain of its users, finds a study published November 25 in Cell Reports. Through experiments conducted ...

Brain connections predict how well you can pay attention

November 24, 2015

During a 1959 television appearance, Jack Kerouac was asked how long it took him to write his novel On The Road. His response – three weeks – amazed the interviewer and ignited an enduring myth that the book was composed ...

Umbilical cells help eye's neurons connect

November 24, 2015

Cells isolated from human umbilical cord tissue have been shown to produce molecules that help retinal neurons from the eyes of rats grow, connect and survive, according to Duke University researchers working with Janssen ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.