Citation

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, Strenzke N, Flügge G, Werner HB, Pawlak R, Nave KA, Ehrenreich H. Transl. Psychiatr. 2013; 3: e254.

Affiliation

1] Division of Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany [2] DFG Research Center for Molecular Physiology of the Brain (CMPB), Göttingen, Germany.

Copyright

(Copyright © 2013, Nature Publishing Group)

DOI

10.1038/tp.2013.28

PMID

23632458

Abstract

Claustrophobia, the well-known fear of being trapped in narrow/closed spaces, is often considered a conditioned response to traumatic experience. Surprisingly, we found that mutations affecting a single gene, encoding a stress-regulated neuronal protein, can cause claustrophobia. Gpm6a-deficient mice develop normally and lack obvious behavioral abnormalities. However, when mildly stressed by single-housing, these mice develop a striking claustrophobia-like phenotype, which is not inducible in wild-type controls, even by severe stress. The human GPM6A gene is located on chromosome 4q32-q34, a region linked to panic disorder. Sequence analysis of 115 claustrophobic and non-claustrophobic subjects identified nine variants in the noncoding region of the gene that are more frequent in affected individuals (P=0.028). One variant in the 3'untranslated region was linked to claustrophobia in two small pedigrees. This mutant mRNA is functional but cannot be silenced by neuronal miR124 derived itself from a stress-regulated transcript. We suggest that loosing dynamic regulation of neuronal GPM6A expression poses a genetic risk for claustrophobia.

Language: en