Novel developments in genetic and epigenetic mechanisms of anxiety

The present review aims to deliver a systematic overview of current developments and trends in (epi)genetics of anxiety and to identify upcoming challenges and opportunities.

Genes related to peptide and hormone signaling have been suggested for anxiety-related phenotypes, e.g., the NPSR1 gene, which has been associated predominantly with panic disorder in women, and shown to interact with environmental factors and to influence psychometric, neurophysiological, and neuroimaging correlates of anxiety. Similar multi-level results have been reported for genetic and epigenetic variation in the OXTR gene, especially in social anxiety disorder (SAD), and for CRHR1 gene variation in women with panic disorder. Variants in RGS2 and ASIC1 genes were linked to panic disorder, with the latter also being implicated in SAD treatment response. Finally, monoaminergic 'risk' genes (SLC6A4, MAOA, HTR1A) were related to SAD, generalized anxiety disorder and women with panic disorder, anxiety traits and response to psychopharmacological and psychotherapeutic interventions.

Converging evidence for potential genetic and epigenetic risk markers has been gathered and future studies call for independent replications and multi-level integration of dimensional approaches, environmental factors, and biological readouts, while considering sex-specific substratification. Particularly, epigenetic variation appears promising for disease course and treatment response predictions.