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Generalized anxiety disorder (GAD) is a common chronic condition that is understudied compared to other psychiatric disorders. An altered adrenergic function has been reported in GAD, however direct evidence for genetic susceptibility is missing. This study evaluated the associations of gene variants in adrenergic receptors ( ADRs ) with GAD, with the involvement of stressful events. Data were obtained from 844 French community-dwelling elderly aged 65 or over. Anxiety disorders were assessed using the Mini-International Neuropsychiatry Interview, according to DSM-IV criteria. Eight single-nucleotide polymorphisms (SNPs) involved with adrenergic function were genotyped; adrenergic receptors alpha(1A) ( ADRA1A ), alpha(2A) ( ADRA2A ), and beta2 ( ADRB2 ) and transcription factor  TCF7L2 . Questionnaires evaluated recent stressful life events as well as early environment during childhood and adolescence. Using multivariate logistic regression analyses four SNPs were significantly associated with GAD. A 4-fold modified risk was found with  ADRA1A rs17426222  and  rs573514,  and  ADRB2 rs1042713  which remained significant after Bonferroni correction. Certain variants may moderate the effect of adverse life events on the risk of GAD. Replication in larger samples is needed due to the small case number. This is the first study showing that  ADR  variants are susceptibility factors for GAD, further highlighting the critical role of the adrenergic nervous system in this disorder.

Preliminary evidence for a role of the adrenergic nervous system in generalized anxiety disorder