Some people 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. Some anxiety attacks occur for no apparent cause. Some patients suffer from the detrimental impacts on their everyday lives, they have problems at work and withdraw from social contacts.

A new study has linked variants of a gene with increased risk of developing anxiety disorders. Mental, social and inherited factors are linked to anxiety disorders and the team pinpointed at least four variants of the GLRB gene (glycine receptor B) as risk factors for anxiety and panic disorders. More than 5,000 voluntary participants and 500 patients afflicted by panic disorder took part in the study that delivered these results, which may be a step toward making anxiety treatment scientific. It will take more than fMRI images, though.

The belief that different variants of the GLRB gene are associated with anxiety disorders might also contribute to the development of improved therapies. The gene had been known to the researchers for some time, albeit only in connection with a different disease.

Activation of the brain's fear network, visualized using functional magnetic resonance imaging. Credit: Dr. Tina Lonsdorf, Systems Neuroscience UKE Hamburg

"Some mutations of the gene cause a rare neurological disorder called hyperekplexia," explains Professor Jürgen Deckert, member of the CRC and Director of the Department of Psychiatry at the Julius-Maximilians-Universität Würzburg University Hospital. The 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 behaviour to avoid potentially frightening situations.

The "fear network" in the brain is activated

But the GLRB gene variants that have recently been associated with anxiety and panic disorders for the first time are different from the ones described above. 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". High-resolution images of the brain activities of study participants provided the clues for the Würzburg scientists.

"The results point to a hitherto unknown pathway of developing an anxiety disorder," Deckert says. He believes that further investigations are now necessary to determine whether these findings can be harnessed to develop new or individual therapies. For example, it is conceivable to bring the "fear network" that is misregulated by the GLRB gene back on track by administering drugs.

Citation: Deckert J1, Weber H1,2, Villmann C3, Lonsdorf TB4, Richter J5, Andreatta M6, Arias-Vasquez A7, Hommers L1,8, Kent L9, Schartner C1, Cichon S10,11,12,13, Wolf C1, Schaefer N3, von Collenberg CR3, Wachter B3, Blum R3, Schümann D4, Scharfenort R4, Schumacher J10,11, Forstner AJ10,11, Baumann C1, Schiele MA1, Notzon S14, Zwanzger P14,15, Janzing JG16, Galesloot T17, Kiemeney LA17, Gajewska A1, Glotzbach-Schoon E6, Mühlberger A18, Alpers G19, Fydrich T20, Fehm L20, Gerlach AL21, Kircher T22, Lang T23,24,25, Ströhle A26, Arolt V14, Wittchen HU23, Kalisch R27, Büchel C4, Hamm A5, Nöthen MM10,11, Romanos M28, Domschke K1, Pauli P6, Reif A2;  “GLRB allelic variation associated with agoraphobic cognitions, increased startle response and fear network activation: a potential neurogenetic pathway to panic disorder”; Molecular Psychiatry, published online on 7 February 2017, DOI: 10.1038/mp.2017.2