Do you panic when you are in a small space? Do you sweat, or shake; does your heart pound? A study in the March issue of Translational Psychiatry reports a genetic defect as the cause of claustrophobia in mice. This is the first time that a single gene has been shown to regulate claustrophobia, moving researchers one step closer to understanding this serious anxiety disorder.

The new research, led by Dr Hannelore Ehrenreich at the Max Planck Institute for Experimental Medicine in Göttingen, Germany, identified a defect in the Gpm6a gene associated with claustrophobia-like behavior in mice and claustrophobia in humans. Results also suggest the same gene could be a potential modifier of other human panic disorders and schizophrenia.

The Gpm6a gene codes for a protein abundant in neurons that was previously known to be affected by stress. The team genetically engineered mice to lack the Gpm6a gene, and that therefore could not produce GPM6 protein. These mice were placed in an Elevated Plus Maze (EPM), a standard test for anxiety in mice, which consists of two enclosed and two open corridors. Rodents avoid open spaces to hide from predators, but "anxious" mice, will instead explore the open corridors. However, the mice lacking Gpm6a preferred the open corridors, regardless of their stress level- a behavior similar to claustrophobia in humans.

It is unethical to perform genetic engineering on humans, so in order to find out whether these findings in mice could apply to humans, the GPM6A genes of claustrophobic and normal human subjects were sequenced and compared. The claustrophobic subjects had more of the rare genetic variations (known as polymorphisms) in their GPM6A genes, suggesting that the regulation of the gene is altered in claustrophobia. The authors suggest that these genetic variants act as claustrophobia-susceptibility genes.

The only known cause for claustrophobia is conditioning, meaning that an affected individual learns a panic response after a traumatic experience. But a large proportion of claustrophobia cases have an unknown cause. This new research shows for the first time that there might be a genetic risk for claustrophobia associated with alterations in a single gene.

Image by Melanie Wasser