Friday, January 04, 2008

Exercise, Genes and Depression

Physical exercise has many health benefits. We often hear about the physical benefits of exercise (e.g. weight reduction, stronger muscles, lower risk of heart disease, etc.) but exercise is also extremely important to your mental health. Recall, for example, this earlier post.

The latest issue of Nature Medicine has a fascinating study on how exercise-regulated genes can induce an antidepressant response. The article is "Antidepressant Actions of the Exercise-Regulated Gene VGF" by Joshua G Hunsberger et. al. So if one needed yet another good reason to make good on one's New Year's resolution to exercise more then read this article. Not only will you likely live a longer, healthier life, you will also be more happy! And you owe it to yourself to promote your physical and mental well being. Here is a sample from the Nature Medicine article:

Exercise has well known cardiovascular benefits; however, it has only recently been documented that exercise also augments brain function and mental health. For instance, exercise enhances hippocampal learning and improves executive functioning in aging humans, while also providing protection from brain insults and disease. In addition, recent studies have shown that exercise produces antidepressant responses in rodent models and mood-elevating actions in humans. The mechanisms underlying the beneficial effects of exercise are not fully understood and could be targets for new therapies that are different from traditional chemical antidepressants.

The antidepressant actions of exercise are particularly noteworthy because of the prevalence of depression (16% in the US population), its enormous economic burden ($83.1 billion per year in the US) and a tremendous need for more effective treatments. Current antidepressant medications are effective for approximately 65% of depressed patients and require long-term treatment for weeks to months before a therapeutic response is achieved.

The time lag in the therapeutic response, in spite of the rapid (hours to days) increase in monoamine levels, has lead to the hypothesis that neural adaptations or plasticity are required. One of the adaptations that may contribute to the actions of antidepressants is the upregulation of neurotrophic factors, most notably brain-derived neurotrophic factor (BDNF), in limbic structures that have been implicated in depression. Notably, exercise also increases the expression of BDNF.

Here we extend these results by using a focused microarray to show that exercise upregulates a primary signaling cascade for neurotrophic factors and a peptide precursor, VGF, that has strong antidepressant efficacy in behavioral models.

....A role for neurotrophic factor signaling and its downstream gene targets in the antidepressant actions of exercise is consistent with a large body of literature showing opposing actions of this pathway in the pathophysiology versus the treatment of depression. The selective induction of VGF by exercise, as well as by ECS, also indicates that there are differences in the molecular mechanisms underlying these treatments in comparison to chemical antidepressants. This highlights the potential importance of VGF as a new endogenous, exercise-regulated target for drug development that could have complementary and possibly even superior efficacy to chemical antidepressants.