The PAC1 receptor risk genotype does not influence fear acquisition, extinction, or generalization in women with no trauma/low trauma.

Women are known to have twice as much lifetime prevalence of post-traumatic stress disorder (PTSD) as men do. It has been reported that the risk genotype (CC) of a single nucleotide polymorphism (SNP) (rs2267735) in the pituitary adenylate cyclase-activating polypeptide (PACAP-PAC1R) system is associated with PTSD risk and altered fear conditioning and fear extinction in women. Surprisingly, no previous work has studied the effect of this SNP on fear conditioning, extinction, or generalization in non-traumatized/low trauma load women. Here, two separate groups of women underwent either a two-day fear conditioning and fear extinction paradigm, or a one-day fear conditioning and fear generalization paradigm. Results showed no significant differences between genotypes in conditioned stimulus discrimination, during fear acquisition, extinction, or generalization. These findings suggest that the previously reported fear processing impairments in traumatized CC women are not a consequence of this genotype alone, but likely dependent on the interaction between this genetic risk and the exposure to traumatic stressors.