Why is change so fearful

A gene that causes panic - Altered gene activity is involved in the development of serious panic attacks

Scientists have now found that some of the patients with panic disorder have mutated a gene and, as a result, change its activity. This genetic change presumably affects the communication between different areas of the brain and can thus trigger uncontrolled feelings of fear.

It starts out of the blue: palpitations, shortness of breath, sweats and tremors. Sudden and massive anxiety and panic attacks without a recognizable trigger are typical symptoms of patients with panic disorders. Around four percent of all people worldwide will suffer from this form of anxiety disorder at some point in their life. There is evidence that genetic factors are involved in the development of panic disorders. "We have not yet understood the causes of such mental disorders down to the last detail, but we have now moved a little closer to the solution," explains Dr. Angelika Erhardt from the Max Planck Institute for Psychiatry in Munich. Together with scientists from the National Genome Research Network (NGFN), the head of the outpatient department for anxiety disorders has identified a gene that is particularly active in the brain and is involved in the development of uncontrolled panic attacks: TMEM132D. "We examined the genetic makeup of more than 900 patients with panic disorders compared to over 900 control persons who do not suffer from anxiety and panic attacks," says Dr. Erhardt. It was shown that the TMEM132D gene is often changed by a mutation in patients with panic disorders. Although only individual components of the gene are swapped, this has immediate consequences: "Patients with panic disorders who carry this risk variant of the TMEM132D gene are afflicted by much more severe panic attacks than patients without this mutation," says Dr. Erhardt. With the TMEM132D gene, the scientists may have discovered a new molecular target for anti-anxiety drugs.

Mutated gene is hyperactive

When examining tissue samples from deceased patients, it turned out that the mutation changes the activity of the gene. "The mutated risk gene is over-activated, so it produces more proteins than necessary - this has been demonstrated in humans in particular for the frontal cortex", describes Prof. Dr. Markus Nöthen from the Institute for Human Genetics at the University Hospital Bonn and member of the NGFN, which is funded by the Federal Ministry of Education and Research. The TMEM132D gene is not only involved in the development and expression of anxiety and panic disorders in humans. Mice whose TMEM132D gene is overactive also behave particularly anxiously. “And here, too, we find increased amounts of TMEM132D protein in fear-relevant brain regions of the animals. This genetic change and its molecular consequences have presumably been preserved through evolution, ”explains Professor Nöthen.

Communication between brain areas disturbed

But how does a higher concentration of TMEM132D proteins in the brain actually trigger a panic attack? "TMEM132D is presumably responsible for the formation of nerve cell connections and thus for the neuronal signal transmission between different areas of the brain," explains Dr. Erhardt. The scientists speculate that too much TMEM132D protein in the brains of patients with panic disorder disrupts this communication. This is because an increased amount of TMEM132D proteins changes the activity in a special area of ​​the frontal cortex, the cingulate cortex, which is important for processing anxiety and fear triggers. The cingulate cortex is closely connected to the emotional center of the brain, the amygdala, which controls our fear behavior. "The increased amount of TMEM132D protein presumably changes the neuronal communication between the cortex and the emotional center and thus promotes the excessive panic attacks," the expert describes.

BMBF brochure "Soul out of balance"

Further information on anxiety disorders and research into mental disorders can be found in the BMBF brochure “Soul Out of Balance - Research into Mental Disorders”.

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Max Planck Institute for Psychiatry
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