New Risk Factors for Anxiety Disorders

Summary: Researchers discover a genetic pathway that could lead to people developing anxiety and panic disorders.

Source: University of Wurzburg.

Mental, social and inherited factors all play a role in anxiety disorders. In the journal “Molecular Psychiatry”, a research team from Julius-Maximilians-Universität Würzburg (JMU) in Bavaria, Germany, describes a hitherto unknown genetic pathway for developing such diseases: They pinpointed at least four variants of the GLRB gene (glycine receptor B) as risk factors for anxiety and panic disorders. More than 5000 voluntary participants and 500 patients afflicted by panic disorder took part in the study that delivered these results.

In Germany, around 15 percent of adults suffer from anxiety and panic disorders. Some people 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 the detrimental impacts on their everyday lives – they often have problems at work and withdraw from social contacts.

How are fear and anxiety triggered? How do anxiety disorders arise and evolve?

Scientists from Münster, Hamburg and Würzburg have looked into these questions within the scope of Collaborative Research Center (CRC) TR 58 funded by Deutsche Forschungsgemeinschaft. Their goal is to develop new therapies that are better tailored to the individual patients. Anxiety disorders can be treated with drugs and behaviour therapy for instance.

Gene triggers hyperekplexia

The discovery 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:

Image shows brain scans with the fear network highlighted in orange.

“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 JMU 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.

ABOUT THIS ANXIETY RESEARCH ARTICLE

Funding: The members of the Collaborative Research Center “Fear, Anxiety and Anxiety Disorders” obtained these results in cooperation with researchers from the “PanikNetz” panic network. The Würzburg team is part of the network that is funded by the Federal Ministry for Education and Research.

Source: Dr. Jürgen Deckert – University of Wurzburg
Image Source: NeuroscienceNews.com image is credited to Dr. Tina Lonsdorf, Systems Neuroscience UKE Hamburg.
Original Research: Abstract for “GLRB allelic variation associated with agoraphobic cognitions, increased startle response and fear network activation: a potential neurogenetic pathway to panic disorder” by J Deckert, H Weber, C Villmann, T B Lonsdorf, J Richter, M Andreatta, A Arias-Vasquez, L Hommers, L Kent, C Schartner, S Cichon, C Wolf, N Schaefer, C R von Collenberg, B Wachter, R Blum, D Schümann, R Scharfenort, J Schumacher, A J Forstner, C Baumann, M A Schiele, S Notzon, P Zwanzger, J G E Janzing, T Galesloot, L A Kiemeney, A Gajewska, E Glotzbach-Schoon, A Mühlberger, G Alpers, T Fydrich, L Fehm, A L Gerlach, T Kircher, T Lang, A Ströhle, V Arolt, H-U Wittchen, R Kalisch, C Büchel, A Hamm, M M Nöthen, M Romanos, K Domschke, P Pauli and A Reif in Molecular Psychiatry. Published online February 7 2017 doi:10.1038/mp.2017.2

University of Wurzburg “New Risk Factors for Anxiety Disorders.” NeuroscienceNews. NeuroscienceNews, 27 February 2017.
<http://neurosciencenews.com/anxiety-risk-factors-6163/&gt;.

Abstract

GLRB allelic variation associated with agoraphobic cognitions, increased startle response and fear network activation: a potential neurogenetic pathway to panic disorder

The molecular genetics of panic disorder (PD) with and without agoraphobia (AG) are still largely unknown and progress is hampered by small sample sizes.

We therefore performed a genome-wide association study with a dimensional, PD/AG-related anxiety phenotype based on the Agoraphobia Cognition Questionnaire (ACQ) in a sample of 1370 healthy German volunteers of the CRC TRR58 MEGA study wave 1.

A genome-wide significant association was found between ACQ and single non-coding nucleotide variants of the GLRB gene (rs78726293, P=3.3 × 10−8; rs191260602, P=3.9 × 10−8).

We followed up on this finding in a larger dimensional ACQ sample (N=2547) and in independent samples with a dichotomous AG phenotype based on the Symptoms Checklist (SCL-90; N=3845) and a case–control sample with the categorical phenotype PD/AG (Ncombined =1012) obtaining highly significant P-values also for GLRB single-nucleotide variants rs17035816 (P=3.8 × 10−4) and rs7688285 (P=7.6 × 10−5).

GLRB gene expression was found to be modulated by rs7688285 in brain tissue, as well as cell culture.

Analyses of intermediate PD/AG phenotypes demonstrated increased startle reflex and increased fear network, as well as general sensory activation by GLRB risk gene variants rs78726293, rs191260602, rs17035816 and rs7688285. Partial Glrb knockout mice demonstrated an agoraphobic phenotype. In conjunction with the clinical observation that rare coding GLRB gene mutations are associated with the neurological disorder hyperekplexia characterized by a generalized startle reaction and agoraphobic behavior, our data provide evidence that non-coding, although functional GLRB gene polymorphisms may predispose to PD by increasing startle response and agoraphobic cognitions.

“GLRB allelic variation associated with agoraphobic cognitions, increased startle response and fear network activation: a potential neurogenetic pathway to panic disorder” by J Deckert, H Weber, C Villmann, T B Lonsdorf, J Richter, M Andreatta, A Arias-Vasquez, L Hommers, L Kent, C Schartner, S Cichon, C Wolf, N Schaefer, C R von Collenberg, B Wachter, R Blum, D Schümann, R Scharfenort, J Schumacher, A J Forstner, C Baumann, M A Schiele, S Notzon, P Zwanzger, J G E Janzing, T Galesloot, L A Kiemeney, A Gajewska, E Glotzbach-Schoon, A Mühlberger, G Alpers, T Fydrich, L Fehm, A L Gerlach, T Kircher, T Lang, A Ströhle, V Arolt, H-U Wittchen, R Kalisch, C Büchel, A Hamm, M M Nöthen, M Romanos, K Domschke, P Pauli and A Reif in Molecular Psychiatry. Published online February 7 2017 doi:10.1038/mp.2017.2

Author: connie dello buono

Health educator, author and enterpreneur motherhealth@gmail.com or conniedbuono@gmail.com ; cell 408-854-1883 Helping families in the bay area by providing compassionate and live-in caregivers for homebound bay area seniors. Blogs at www.clubalthea.com Developing a new site, www.avatarcare.net , for early cancer detection using genetics tests, telemedicine with electronic appointment scheduling with doctors, video chat with doctors, matching care providers with health consumers and a health concierge for all to reduce chronic care cost, find cancer cure and coordinate health care using predictive medicine and participatory.

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