Genetics of panic disorder: focus on association studies and therapeutic perspectives

There is evidence for either genetic heterogeneity or complex inheritance with an interaction of environmental factors and multiple single genes in the etiology of panic disorder. Although linkage analyses of panic disorder have implicated several chromosomal regions including 1q, 2q, 4q, 7p, 9q, 12q, 13q, 15q and 22q, they so far have not been able to identify a major gene responsible for panic disorder. Several genes of classical candidate neurotransmitter systems have been reported to be associated with panic disorder. Genetic variation in genes of monoamine oxidase A, catechol-O-methyltransferase, adenosine receptor (ADORA2A) and cholecystokinin B receptor have been inconsistently replicated. There are multiple lines of evidence for highly relevant effects of gender and ethnicity. Future research strategies might focus on broad phenotypes defined by comorbidity or intermediate phenotypes and include the use of animal models for identifying candidate genes, such as the regulator of G-protein signaling (RGS2) gene, genome-wide association studies in large samples, studies of gene-gene and gene-environment interactions and pharmacogenetic studies. The identification of novel pathophysiological pathways may provide the basis for the development of novel therapeutic interventions.