As a little girl, my favorite part of an overnight train journey in India was the tunnel. My restless, anxious eyes would await the moment when the train made its grand entry into the gigantic passageway only to excitedly celebrate the “light at the end of the tunnel,” quite literally! But one summer, things were slightly different – the train hit a red light and its rear end remained buried inside the pitch-dark tunnel for longer than usual. While my rational sense knew that it was only a matter of seconds before the train started again, an irrational fear of being trapped inside overcame me. It was then that I learned of a form of fear that 1 in 20 people around the world have – claustrophobia – the fear of enclosed spaces.

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Like most phobias, claustrophobia can arise from an early childhood experience, where a child begins to associate danger with being trapped in, say, a dark room. These anecdotal evidences form the classical conditioning of claustrophobia. More recently, the genetic underpinnings of several anxiety disorders have corroborated the theory of genetic predisposition, where altered gene expressions make an individual more prone to having a phobia. Although no genetic predisposition was known for claustrophobia, scientists at the Max Planck Institute recently stumbled upon a single gene that may be critically involved with developing the phobia.

Gpm6a gene, which encodes a neuronal membrane glycoprotein, has been previously implicated as a gene regulated by psychosocial stress. The team of El-Kordi et al. created a genetically modified mouse where the Gpm6a was removed from the mouse’s genome (Gpm6a knockout mouse). The researchers then put the mice through multiple behavioral tests to determine what role the Gpm6a gene played in the stress response. The results of one test, however, raised eyebrows.

The elevated plus maze is a behavioral test that is used to test the anxiety of mice. The set up consists of a plus shaped catwalk that is elevated off the ground where two of the arms are enclosed by walls and two are open (see figure below). Generally, mice have an innate tendency to avoid open areas and prefer enclosed spaces. If the mouse is more anxious, it will typically spend very little time exploring the open arms and stay within the safety of the closed arms. The Gpm6a knockout mice, however, spent most of their time in the open arms, a behavior that goes against the natural instinct of most mice. In fact, all Gpm6a knockout mice seemed to behave in the same way regardless of their stress or anxiety level. The researchers termed this preference to be a claustrophobic trait. The results of their study showed that any form of stress on Gpm6a knockout mice, be it mild or strong, caused them to become incredibly claustrophobic.

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To see if the Gpm6a gene was also important for claustrophobia in humans, the research team analyzed the DNA sequence of the human GPM6A gene in 115 claustrophobic and normal individuals. Surprisingly, the claustrophobic individuals showed genetic variations in the GPM6A gene, suggesting its altered expression. This is the first time in neuroscience that a single gene has been found to regulate claustrophobia!

Although the detailed mechanism of the Gpm6A/GPM6A gene is yet to be studied, the authors term this gene as a neuronal ‘brake’ to maintain a healthy stress response. Exploring the genetics of highly prevalent phobias, like claustrophobia, may provide a deeper understanding of their causes and can hopefully help psychiatrists treat these disorders, enabling claustrophobic individuals to be anxiety-free in a day-to-day confrontation of an enclosed space like the elevator.

Reference:

El-Kordi A., Kästner A., Grube S., Klugmann M., Begemann M., Sperling S., Hammerschmidt K., Hammer C., Stepniak B., Patzig J. & de Monasterio-Schrader P. (2013). A single gene defect causing claustrophobia, Translational Psychiatry, 3 (4) e254. DOI: 10.1038/tp.2013.28

Images made by Anita Ramanathan

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