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Research yields potential new direction for anxiety treatment

With anxiety disorders among the most prevalent mental illnesses in the United States, a study published in Molecular Psychiatry on Tuesday found that blocking a stress hormone in a specific part of the brain could help treat them.

According to the National Institute of Mental Health, anxiety disorders affect about 18 percent of the population of the United States. Anxiety can take many forms, including generalized anxiety, obsessive-compulsive disorder and specific phobias. Women are 60-percent more likely than men to experience an anxiety disorder and the average age of onset is 11 years old.

The study was performed by researchers Dr. Joseph Majzoub and Dr. Rong Zhang in the Division of Endocrinology at Boston Children’s Hospital. They investigated the effect of blocking a stress hormone called corticotrophin-releasing hormone in the area of the brain known as the hypothalamus.

The hypothalamus is responsible for releasing hormones that regulate thirst, hunger, sleep and other basic functions. When it perceives a threat, it releases stress hormones that prime the body to respond. Fear in the face of threats is natural, but anxiety disorders manifest as more generalized feelings of worry and tension that interfere with daily activities.
Researchers have known for almost 40 years that CRH co-ordinates the physical and behavioral stress response. Several drug companies have developed drugs that block CRH, but the results have not been encouraging. In a media release from Boston Children’s Hospital, Majzoub said six of the eight completed phase II and III trials of medications that block CRH have had negative findings, meaning they did not satisfactorily address anxiety symptoms.

These earlier studies blocked CRH throughout the brain. Zhang thought that a more focused approach might be more effective.  

“Blocking CRH receptors all over the brain doesn't work,” Zhang said in the press release. “We think the effects work against each other somehow. It may be that CRH has different effects depending on where in the brain it is produced.”

So Zhang and Majzoub removed the CRH gene from the nerve cells of mice, targeting only those cells in the hypothalamus. Hormone secretion was reduced as expected, but researchers were surprised to find that anxiety behaviors were also reduced. So mice were less fearful and more willing to explore areas they might otherwise avoid, such as an elevated platform, an open field, and brightly lit areas.

“It was a very robust finding: Every parameter we looked at indicated that this animal was much less inhibited,” Majzoub said in the release.

Dr. Mark Pollack, chairman of the department of psychiatry at Rush University Medical Center, told AMI Newswire the results are interesting and he knows of no other studies examining the potential of blocking CRH production this way.

“Given that CRH-blocking agents that work broadly across the brain have thus far not been reliably effective when tested for anxiety and depression, the challenge will be to develop and test agents that work specifically in the hypothalamus to see if their anti-anxiety and antidepressant effects may be more robust,” Pollack told AMI.

Current treatments for anxiety include psychotherapy, particularly cognitive behavioral therapy, which teaches the patient to think and behave in ways that help them overcome anxiety, and medications such as antidepressants, bonzodiaxepines and beta blockers, which generally reduce the symptoms of anxiety.

The CRH study represents a potential new direction for treatment, but more study is needed before it can be used on humans.

“Blocking just certain neurons releasing CRH would be enough to alter behavior in a major way,” Majzoub said in the release. “We don't know how to do that, but at least we have a starting point.”