Two of the most frightening and common symptoms of panic attacks are feelings of shortness of breath and a sense of suffocation. Breathing air with increased levels of carbon dioxide can actually trigger panic attacks in most people with panic disorder, but not in people without the disorder, studies have shown.

Panic disorder is an acute form of anxiety. It begins with feeling a sudden rush of fear, often along with intense physical discomfort symptoms.

Another factor scientists know the disorder, about from studying twins, is that genes contribute to the risk of panic disorder, but very little is known about which specific genes are involved.

Panic Suffocation Alarm Theory

[caption id=“attachment_11873” align=“alignright” width=“199”] By: Adam Selwood[/caption]

The biological specifics of how carbon dioxide inhalation produces anxiety are also not well understood. One theory proposes that panic disorder involves an overly sensitive suffocation alarm system in the brain. Such a center would have evolved in order to protect us from suffocating.

Panic attacks, the theory goes, result when this alarm gets triggered by signals of impending suffocation like rising carbon dioxide levels.

Earlier research found in mice a protein called ASIC1a that indirectly acts as a carbon dioxide sensor in the amygdala. The amygdala is a region in the brain critical to the perception of danger and fear.

The mice’s ASIC1a gene was found to regulate carbon-dioxide induced anxiety.

Now, an international collaborative group of researchers has researched the human version of the ASIC1a gene, ACCN2.

Researchers genotyped and compared variants in ACCN2 in 414 individuals with panic disorder and 846 healthy controls.

In a control group of healthy individuals, genotyping and neuroimaging was used to look at possible genetic associations with amygdala volume in 1048 subjects and amygdala function in a subset of more than 100 subjects.

“We found that different forms or variants of the human ASIC1a gene appear to be associated with panic disorder. The effect was stronger in those whose panic attacks have prominent respiratory symptoms, including shortness of breath and feelings of suffocation,” explained Dr. Jordan W. Smoller, co-senior author.

“Next, we found that the panic-associated variants in the ASIC1a gene are also associated with both the size of the amygdala and a greater amygdala response to emotional threat, even in people without panic disorder."

Genetic Risks for Panic Disorder

Dr. Bruce M. Cohen, co-senior author said:

“Taken together, our results suggest that the ASIC1a gene is a risk gene for panic disorder, as well as for the structure and function of the amygdala and its reaction to threat. They also raise the possibility that drugs that inhibit or modulate ASIC1a might be helpful in the treatment of panic or other forms of anxiety and fear."

A number of studies show the amygdala has a considerable role in mental states, and is related to many psychological disorders.

Some have shown children with anxiety disorders tend to have a smaller left amygdala. In the majority of the cases, there was an association between an increase in the size of the left amygdala with the use of SSRIs (antidepressant medication) or psychotherapy.

The left amygdala has been linked to social anxiety, obsessive and compulsive disorders, and post traumatic stress, as well as more broadly to separation and general anxiety

Dr. John Krystal, Editor of Biological Psychiatry, commented:

“Once again we see that a mechanism that is implicated in the generation of fear and the risk for anxiety disorders has its basis in a fundamental survival mechanism. This important new study continues to build our understanding of the underpinnings of anxiety disorders that affect so many people in our society."

More information:

Jordan W. Smoller, Patience J. Gallagher, Laramie E. Duncan, Lauren M. McGrath, Stephen A. Haddad, Avram J. Holmes, Aaron B. Wolf, Sidney Hilker, Stefanie R. Block, Sydney Weill, Sarah Young, Eun Young Choi, Jerrold F. Rosenbaum, Joseph Biederman, Stephen V. Faraone, Joshua L. Roffman, Gisele G. Manfro, Carolina Blaya, Dina R. Hirshfeld-Becker, Murray B. Stein, Michael Van Ameringen, David F. Tolin, Michael W. Otto, Mark H. Pollack, Naomi M. Simon, Randy L. Buckner, Dost Öngür, and Bruce M. Cohen “The Human Ortholog of Acid-Sensing Ion Channel Gene ASIC1a Is Associated with Panic Disorder and Amygdala Structure and FunctionBiological Psychiatry Volume 76, Issue 11 DOI: 10.1016/j.biopsych.2013.12.018

Holmes, A.J., Lee, P.H., Hollinshead, M.O., Bakst, L., Roffman, J.L., Smoller, J.W. et al. Individual differences in amygdala-medial prefrontal anatomy link negative affect, impaired social functioning, and polygenic depression risk. J Neurosci. 2012; 32: 18087–18100

Shin, L.M. and Liberzon, I. The neurocircuitry of fear, stress, and anxiety disorders. Neuropsychopharmacology.2010; 35: 169–191

Top Photo by Mat Honan

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