Variation in the candidate genes adenosine A2A receptor (A2AR), catechol-O-methyl-transferase (COMT), and norepinephrine transporter (NET) has been suggested to influence vulnerability to panic disorder. We therefore investigated patients with another anxiety disorder with an even higher heritability, the blood-injury phobia, for association of these variants and used sympathetic measures during venipuncture, which serve as a naturalistic trigger of anxiety and autonomic hyperarousal, as an intermediate phenotype of anxiety.
Patients homozygous for the A2AR 1976T allele as compared to patients carrying at least one 1976C allele exhibited a significantly increased respiratory rate with a trend towards elevated measures of systolic and diastolic blood pressure and respiratory minute volume. None of the sympathetic measures were influenced by the COMT or NET polymorphisms.
This study provides preliminary data suggesting an influence of the A2AR 1976C/T polymorphism on sympathetic psychophysiological indicators of anxiety-related arousal in blood-injury phobia and thereby further supports a role of the A2AR gene in the pathogenesis of anxiety disorders.