Dysregulated Gene Expression: A Candidate Mechanism for Anxiety Disorders.

Abstract

Anxiety disorders are among the most prevalent and debilitating mental illnesses worldwide. While environmental factors such as early-life stress contribute to their etiology, genetics also plays a crucial role, with a family history increasing susceptibility. Unlike Mendelian traits driven by single gene variants, anxiety disorders appear to follow polygenic inheritance in which multiple genetic variants collectively shape risk. Genome-wide association studies (GWAS) have identified numerous loci linked to anxiety, yet individual variants have small effect sizes and leave much of the heritability unexplained. A clue to resolving this conundrum may lie in the fact that most GWAS hits reside in non-coding regions with characteristics of gene-regulatory elements. This observation raises the possibility that altered expression of otherwise normal genes contributes to susceptibility. Gene-regulatory elements control when and where genes are expressed. Disruption of these elements may contribute to anxiety disorders by subtly altering neuronal signaling and stress-response pathways. Unraveling the role of gene regulation in anxiety disorders presents a promising avenue for improved diagnosis and targeted treatments. This review explores recent advances in the field and their potential for understanding the genetic architecture of anxiety disorders.