title: Stressing over anxiety: A novel interaction of 5-HTTPLR genotype and anxiety-related phenotypes in older adults.
abstract: Variation within the serotonin transporter gene-linked polymorphic region (5-HTTPLR) contributes to individual differences in trait neuroticism and increases risk for the development of psychopathology in the context of stressful life events. The underlying mechanisms may involve dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis and the release of stress-related hormones. Yet, observed effects are small, possibly because they occur against the background of many other, mostly unknown, genetic and environmental variables. In this study, we removed much of the variance contributed by such background factors by including complex trait and behavioral measures in our analyses, to isolate the unique contributions of 5-HTTLPR genotype to cortisol baseline, reactivity, and recovery during the Trier Social Stress Test. We recruited 82 community-dwelling older adults (55 and older), an under-studied population, and measured salivary cortisol levels at baseline and following the TSST. As a comparison group we also recruited 88 younger adults (males only, 18-51 years old). Neuroticism, trait anxiety, perceived stress levels, and early childhood trauma experiences were measured using self-report questionnaires. An exploratory factor analysis revealed a latent anxiety trait. Cortisol baseline levels were significantly elevated in older adult S-allele carriers (but not in LL-homozygotes) who scored higher on the latent anxiety trait, relative to S-allele carriers. No such differences were found among younger adults, nor amongst measures obtained during the reactivity or recovery periods. These results highlight the utility of taking into account background variables that may otherwise obscure associations between genetic variables and endophenotypes.
authors.affiliation: Department of Psychology, Stony Brook University, Stony Brook, NY, 11794-2500, USA.
authors.forename: Nia
authors.initials: N
authors.lastname: Fogelman
authors.affiliation: Department of Psychology, Stony Brook University, Stony Brook, NY, 11794-2500, USA.
authors.forename: Anatoly
authors.initials: A
authors.lastname: Mikhailik
authors.affiliation: Department of Psychology, Stony Brook University, Stony Brook, NY, 11794-2500, USA.
authors.forename: Anett
authors.initials: A
authors.lastname: Mueller-Alcazar
authors.affiliation: Department of Psychology, Stony Brook University, Stony Brook, NY, 11794-2500, USA.
authors.forename: Kristin
authors.initials: K
authors.lastname: Bernard
authors.affiliation: Department of Psychology, Stony Brook University, Stony Brook, NY, 11794-2500, USA. Electronic address: turhan.canli@stonybrook.edu.
authors.forename: Turhan
authors.initials: T
authors.lastname: Canli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001007:Anxiety / Q000503:physiopathology / Q000523:psychology; D001008:Anxiety Disorders / Q000378:metabolism; D005260:Female; D005838:Genotype; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis; D007030:Hypothalamo-Hypophyseal System; D008016:Life Change Events; D008297:Male; D008875:Middle Aged; D000075384:Neuroticism; D010641:Phenotype; D010913:Pituitary-Adrenal System; D012463:Saliva; D057566:Self Report; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D013315:Stress, Psychological / Q000503:physiopathology* / Q000523:psychology*; D011795:Surveys and Questionnaires
chemical_list: C493230:SLC6A4 protein, human; D050486:Serotonin Plasma Membrane Transport Proteins; D006854:Hydrocortisone
keywords: Anxiety; Cortisol; HPA axis; Neuroticism; Serotonin; Stress