New Genetic Risk Factor Identified for Anxiety Disorders

Several newly discovered variants of the GLRB gene were associated with increased risk of developing anxiety disorders, including agoraphobic cognitions, increased startle response, and fear network activation, pointing to a potential neurogenetic pathway.

Mental, social, environmental, and inherited factors play roles in development of anxiety disorders. The study, conducted by a research team from Julius-Maximilians-Universität Würzburg (JMU; Würzburg, Bavaria, Germany), involved over 5000 voluntary participants and 500 patients afflicted by panic disorder. The researchers pinpointed at least 4 variants of the GLRB (glycine receptor B) gene as risk factors for anxiety and panic disorders. High-resolution images of the brain activities of study participants provided additional clues.

Among people who suffer from anxiety and panic disorders, some may have an extreme fear of spiders or other objects, while others have breathing difficulties and accelerated heart beat in small rooms or large gatherings of people. With some afflicted persons, the anxiety attacks occur for no apparent cause. Many patients suffer from detrimental impacts on their everyday lives, often having problems at work and withdrawing from social contacts.

How are fear and anxiety triggered? How do anxiety disorders arise and evolve? Scientists from Münster, Hamburg, and Würzburg have been looking into these questions within the scope of the Deutsche Forschungsgemeinschaft (DFG)-funded Collaborative Research Center (CRC) TR 58. CRC members obtained the new results in cooperation with researchers from the "PanikNetz" panic network (Germany).

GLRB had been known for some time in connection with a different disease: "Some mutations of the gene cause a rare neurological disorder called hyperekplexia," said Prof Jürgen Deckert, of the CRC and JMU University Hospital. Hyperekplexia patients are permanently hypertonic and show pronounced startle responses, which may even cause sufferers to fall involuntarily. Similar to persons suffering from anxiety disorders, these patients develop behavior to avoid potentially frightening situations.

The GLRB mutations that have now for the first time been associated with anxiety and panic disorders are different from those of hyperekplexia. They occur more frequently and presumably entail less severe consequences. But they, too, trigger overshooting startle responses, and as a result may excessively activate the brain's "fear network".

"The results point to a hitherto unknown pathway of developing an anxiety disorder," said Prof Deckert. Further investigations are necessary to determine whether these findings can be harnessed to develop new therapies. For example, it is conceivable to bring the "fear network" that is misregulated by the GLRB variants back on track by administering drugs, possibly in addition to psychology-based behavior therapy.

The study, by Deckert J et al, was published online February 7, 2017, in the journal Molecular Psychiatry.