FGF2: Promising New Treatment for Anxiety, Depression and Stress?

According to the National Institutes of Health, about 40 million Americans adults suffer from anxiety disorders, 15 million deal with major depression on a daily basis, and millions more have milder or intermittent symptoms of both. It is not generally appreciated that depression is the leading cause of disability in the 15 to 44 age group, and is responsible for ninety percent of the 32,500 suicides/year. Depression is much more prevalent in women, and while they attempt suicide two or three times more often than men, suicide deaths are actually four times higher in men, the highest rates being seen in white males over age 85.* What accounts for these disparities, and is it possible to predict who is at increased risk?

Since anxiety and depression frequently co-exist, many believe that they share one or more common causes. Researchers had previously demonstrated that people with severe depression had low levels of FGF2 (fibroblast growth factor 2) and other related chemicals. However, it was unclear whether these caused or resulted from the disease. To investigate this, the same group studied rats that had been selectively bred to exhibit high or low anxiety behaviors for over 19 generations. Consistent with the human depression studies, the researchers found much lower FGF2 levels in rats bred for high anxiety compared to those bred for low anxiety. In addition, when FGF2 was administered to high anxiety animals, their symptoms were sharply reduced, providing support for a causal role. Other researchers had previously shown that anxiety behaviors in rats could be reduced by making certain changes to their environment that would be considered similar to improving lifestyle changes for people. This study confirmed the beneficial effects of environmental enrichment and also showed that it increased FGF2 levels.

But how does FGF2 reduce anxiety and depression? It has long been known that depressed patients as well as those suffering from other stress related disorders like PTSD have memory problems, especially for recent events, similar to what is usually seen in the elderly. This memory deficit is associated with atrophy of the hippocampus, a portion of the brain responsible for storing and retrieving memories, and has been attributed to increased amounts of the stress hormone cortisol that are commonly seen in depression. It has been shown that depression decreases the production of new cells in the hippocampus and other parts of the brain, but this new study found that high and low anxiety animals produced the same number of brain cells. However, new brain cells in high anxiety animals did not survive nearly as long as those from the low anxiety strain, and this could also be reversed by FGF2 and environmental enrichment.

As the lead author said, ” This is surprising, as FGF2 and related molecules are known primarily for organizing the brain during development and repairing it after injury. We have discovered that FGF2 has two important new roles: it’s a genetic vulnerability factor for anxiety and a mediator for how the environment affects different individuals.” Another expert on anxiety and neurogenesis not involved in the study, was even more enthusiastic, noting, “This discovery may pave the way for new, more specific treatments for anxiety that will not be based on sedation – like currently prescribed drugs – but will instead fight the real cause of the disease.” While the clinical applications of this new discovery may be years away, environmental enrichment programs that are much safer and in some cases more effective than drugs are readily available, and one has helped over a million people with anxiety and depression over the past decade.**


Perez JA, Clinton SM et al. A New Role for FGF2 as an Endogenous Inhibitor of Anxiety. The Journal of Neuroscience, May 13, 2009, 29(19):6379-6387


** www.stresscenter.com