Depression is an astonishingly common mental disorder; it affects as many as 1 in 4 people during their lifetime, and between 5 and 10% of the population are suffering from the illness to some extent at any one time.
Despite extensive research into this area, the underlying causes of depression are not well understood, although many believe it could stem from changes in brain chemistry. In particular, two chemicals have taken center stage: dopamine and serotonin, which are often found in lower levels in patients with depression. However, it is becoming increasingly apparent that this could be a symptom rather than a cause.
Another molecule that has recently piqued the interest of scientists is a protein called beta-catenin. β-catenin is known to play a variety of roles in the central nervous system, and its malfunction has been implicated in numerous mental illnesses, including depression. Supporting these links, a newly published study has suggested that our brain’s ability to cope with stress and resist depression is determined, at least in part, by the activity of this protein. These findings challenge current ideas about the etiology of depression and could eventually lead to novel and potentially more effective ways to treat the disorder.
As described in Nature, scientists from the Icahn School of Medicine started off by exposing mice to chronic social stress, which caused some animals to exhibit depression-like symptoms. They then examined their brains to see if any notable differences could be identified, and found a disparity in the levels of active β-catenin between mice that were resistant or susceptible to stress.
More specifically, they found the mice that showed resilience to stress possessed more active β-catenin in the brain’s reward and motivation center, the nucleus accumbens (NAc). Conversely, those that succumbed to stress and developed signs of depression were found to have inactive β-catenin in the NAc.
In support of this, the researchers also found suppression of this protein in the brain tissue of deceased patients that had suffered from depression, regardless of whether they had been taking antidepressants at the time of death.
Further examination revealed that the pro-resilient effects observed in the mice were mediated through interactions between β-catenin and a type of dopamine receptor called a D2 receptor. Taking this forward, the researchers blocked β-catenin from being able to interact with D2 receptors in mice that had previously shown resilience to depression, which rendered them susceptible to stress. Similarly, activating β-catenin in susceptible mice made them more resilient to depression after exposure to stress.
Lastly, by snipping out β-catenin from NAc neurons and examining the resulting gene expression patterns, the researchers were able to identify a network activated by β-catenin that is associated with resilience. Specifically, they found that β-catenin targets a gene called Dicer1 which produces a protein that plays key roles in regulating the expression of other genes. How these genes affect depression, however, remains unknown at the moment.
Although more work needs to be done, these initial findings suggest that targeting β-catenin could lead to a novel way to treat depression. Rather than undoing the negative impacts of stress, scientists may be able to activate natural resilience mechanisms.