The regulation of corticotropin releasing hormone receptor 1 gene expression and its role in panic disorder

Authors: Schartner, Christoph;
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Abstract

Panic Disorder (PD) is characterized by unexpected, recurrent panic attacks, which are not restricted to certain situations, medication or stimuli. Like other anxiety disorders, PD is a multifactorial disorder and develops through the interaction of genetic and environmental risk factors. Despite an estimated heritability of up to 48%, no distinct genetic mechanism could be revealed yet. A dysregulation of the stress response has been shown in patients with PD and several studies could find an association of components of the corticotropin-releasing factor (CRF) system with PD. The corticotropin releasing hormone receptor 1 (CRHR1) is the main receptor of CRF in the brain and thus a crucial regulator of cerebral CRF signaling. Recent genetic studies found an association of certain CRHR1 single nucleotide polymorphisms (SNPs) with PD and other anxiety disorders. Among the associated CRHR1 SNPs, rs17689918 showed further evidence in a multilevel study regulating CRHR1 gene expression in panic-relevant brain regions and affecting brain activation in fMRI experiments, as well as flight behavior in a behavioral avoidance task (Weber et al, 2015). Here, we aimed to investigate the underlying neurogenetic and neurobiological mechanisms, by which the rs17689918 risk allele affects CRHR1 gene expression and receptor function, and its putative function in the pathophysiology of PD.