Genes Behind Anxiety Identified

Overexpression of Crh and Oprm 1 genes is responsible for anxiety and behavioral problems, say scientists.

The genes (Crh [corticotropin-releasing hormone] and Oprm 1 [mu-opioid receptor MOR 1]) may point the way to treating these problems in patients with too much of the protein, said scientists at the Baylor College of Medicine.

MeCP2 is a "Goldilocks" in the protein world. When the protein is lacking or defective, girls develop the neurological disorder Rett syndrome early in life.

Too much protein results in the more recently identified MeCP2 duplication syndrome, which usually affects boys, who may inherit the gene duplications either from their mothers or, in rare cases, develop it sporadically.

In both cases, anxiety and social behavioural deficits are typical of those with the disease, along with other motor problems and cognitive defects.

"This is a nice example of a translational story," said Dr. Rodney Samaco, assistant professor of molecular and human genetics at BCM and first author of the study.

"We first identified the mouse model for MeCP2 duplication syndrome and then found people with the disorder in the clinic. We went back to the lab and found out that MeCP2 was indeed the major contributor to this phenotype in patients.

"We have now identified two genes involved in two major symptoms of the syndrome. Eventually, we may take the information back to the clinic to develop a treatment for patients," Samaco stated.

Patients with MeCP2 duplication disorder have a duplication in chromosomes that span both the MECP2 gene and another called IRAK1. But with this new study, it is now clear that excess MeCP2 accounts for the neuropsychiatric symptoms.

This finding is important because it shows that tweaking the expression of genes that the protein affects, rather than trying to adjust the levels of the finicky MeCP2 protein itself, can modify symptoms of MeCP2 disorders.

The finding appeared online in the journal Nature Genetics.

Source-ANI