Genetic, epigenetic and environmental interaction in panic disorder

Panic disorder (PD) is the most common heritable anxiety disorder; there is a three- to eight-fold increased risk of panic disorder among relatives of panic disorder patients versus relatives of non-affected individuals. Family studies, twin studies, and combined models have revealed that the heritability estimate for panic disorder is 0.48. Linkage analyses and genetic association studies have made progress in identifying genetic risk factors for panic disorder. However, the remaining 52% of risk for developing PD is attributable to individual environmental factors, highlighting the complex genetic nature of panic disorder. Psychosocial factors have been explored using cognitive behavioral theories and classic conditioning approaches. Epigenetic processes have also been shown to critically influence gene regulation and mediate the impact of environmental factors in mental disorders and thus have been suggested as a necessary complement to genetic analyses of complex-genetic disorders. DNA hypomethylation of glutamate decarboxylase 1 (GAD1) or the monoamine oxidase A (MAOA) gene might play a role in the manifestation of panic disorder based on geneenvironment interactions.