Stress, Anxiety and Depression Link Uncovered

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Could scientists at the University of Western Ontario be on the trail of a new way and effective to treat depression? That is one of the possibilities with the discovery of the biological link that shows how stress and anxiety could lead to depression.

Despite the massive amount of research into the causes, prevention, and treatment of depression, scientists still have many unanswered questions, and treatments still leave much to be desired. A study that evaluated 47 clinical trials, for example, found that prescribed antidepressants including Prozac, Effexor, Serzone, and Seroxat were barely more effective than placebo. The authors noted that “Given these results, there seems little reason to prescribe antidepressant medication to any but the most severely depressed patients unless alternative treatments have failed to provide a benefit.”

A recent meta-analysis published in the Journal of the American Medical Association found that the efficacy of antidepressants “were nonexistent to negligible” among patients who had mild, moderate, and even severe symptoms of depression. The drugs did, however, help people who had the most severe symptoms.

The scientists from Western Ontario used a behavioral mouse model and molecular experiments that ultimately lead to the discovery of the connection pathway between stress and anxiety and depression. They also tested a new small molecule inhibitor developed by Stephen Ferguson of Robarts Research Institute, and one of the study’s authors . The inhibitor may provide an improved approach to treatment of anxiety, depression, and related disorders.

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The scientists’ research showed a link between two substances: corticotrophin releasing factor receptor 1 (CRFR1) and specific types of serotonin receptors (5-HTRs). They found that CRFR1 increases the number of 5-HTRs on the surface of cells in the brain, which can lead to abnormal signals. Because CRFT1 activation leads to anxiety in response to stress and 5-HTRs lead to depression, the scientists discovered how stress, anxiety, and depression pathways connect through these specific processes in the brain.

In addition, the inhibitor that Ferguson developed blocks 5-HTRs and thus fights anxious behavior, and potentially depression, in mice. The next step, says Ferguson, “is to see whether or not we can take the inhibitor we developed and turn it into a pharmaceutical agent.”

A new, effective pharmaceutical agent would be welcomed by many, given the questionable performance of available medications. The National Institute of Mental Health reports that approximately 14.8 million American adults have major depressive disorder, and that an additional 3.3 million have chronic, mild depression (dysthymic disorder). Major depression disorder is the leading cause of disability in the United States for people ages 15 to 44.

The discovery of the link between stress, anxiety, and depression is an important breakthrough, the first biological evidence of this connection. In addition, Ferguson’s molecule inhibitor may provide a new, more effective way to treat anxiety, depression, and related conditions.

SOURCES:
Fournier JC et al. Journal of the American Medical Association 2010; 303(1): 47-53
Kirsch I et al. PLoS Med 2008 Feb; 5(2): e45
National Institute of Mental Health
University of Western Ontario

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