title: Preliminary evidence for a role of the adrenergic nervous system in generalized anxiety disorder.
abstract: 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.
authors.affiliation: Inserm, U1061, Montpellier, France.|Univ Montpellier, Montpellier, France.|Tianjin Mental Health Center, Tianjin, China.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Inserm, U1061, Montpellier, France.|Univ Montpellier, Montpellier, France.
authors.forename: Joanna
authors.initials: J
authors.lastname: Norton
authors.affiliation: Inserm, U1061, Montpellier, France.|Univ Montpellier, Montpellier, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Carrière
authors.affiliation: Inserm, U1061, Montpellier, France.|Univ Montpellier, Montpellier, France.|Faculty of Medicine, Imperial College, London, UK.
authors.forename: Karen
authors.initials: K
authors.lastname: Ritchie
authors.affiliation: Inserm, U1061, Montpellier, France.|Univ Montpellier, Montpellier, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Chaudieu
authors.affiliation: Inserm, U1061, Montpellier, France.|Univ Montpellier, Montpellier, France.|Disease Epigenetics Group, Murdoch Children's Research Institute, and Department of Paediatrics, The University of Melbourne, Parkville, Australia.
authors.forename: Joanne
authors.initials: J
authors.lastname: Ryan
authors.affiliation: Inserm, U1061, Montpellier, France.|Univ Montpellier, Montpellier, France.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Ancelin
mesh_terms: D018663:Adrenergic Agents / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D001008:Anxiety Disorders / Q000175:diagnosis / Q000209:etiology* / Q000378:metabolism* / Q000523:psychology; D005260:Female; D005838:Genotype; D006801:Humans; D008016:Life Change Events; D008297:Male; D010698:Phobic Disorders / Q000235:genetics / Q000378:metabolism / Q000523:psychology; D020641:Polymorphism, Single Nucleotide; D011941:Receptors, Adrenergic / Q000235:genetics / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000378:metabolism*
chemical_list: D018663:Adrenergic Agents; D011941:Receptors, Adrenergic