ADRB2 gene polymorphism modulates the retention of fear extinction memory

Individual differences in regulation of fear and extinction memory play significant roles in the aetiology development of post-traumatic stress disorder (PTSD). Previous animal based studies showed that the activity of β-adrenergic receptors (β-ARs) are involved in memory modulation. However in humans it is not clear that whether genetic variability in β-ARs contributes to individual differences of fear and extinction memory. In the current study, we investigated the role of a common single-nucleotide polymorphism of β₂-adrenergic receptor (ADRB2) gene in fear memory acquisition, fear memory extinction, extinction recall and fear generalization in human participants. Ninety-one male participants were exposed to a Pavlovian fear conditioning and their fear responses were assessed by the skin conductance response. Participants were genotyped for a polymorphism (rs2400207) located within the promoter region of the human ADRB2. Differences between genotypes were observed in the extinction memory recall test but not in fear acquisition, extinction learning and fear generalization. Particularly, A-allele carriers of rs2400707 displayed successful retention of extinction memory and prevented the return of fear during recall test. The results revealed the involvement of human noradrenergic system in the retention of extinction memory and genetic variability in this system may underlie individual differences in PTSD. Furthermore, rs2400207 polymorphism of ADRB2 gene may play a key role in the treatment efficacy of PTSD and can be a basis for future studies investigating a personalized medicine for fear memory related disorders.