title: Heterogeneity in HPA axis dysregulation and serotonergic vulnerability to depression.
abstract: Variability in the serotonin transporter (5-HTTLPR) gene can influence the risk of depression associated with adversity, as well as cortisol stress reactivity, although not consistently. No study has examined the impact of both a stressful environment and corticotropic-axis dysfunction on depression, as a function of 5-HTTLPR. This population-based study included 334 subjects aged 65 and older. Depression was measured at both diagnostic (major depression according to DSM-IV) and symptomatic (subthreshold depression) levels of caseness, in addition to 5-HTTLPR and rs25531 genotyping and diurnal cortisol measures. For participants with the SS genotype, higher morning cortisol levels were associated with a 4-fold increased risk of depression. Among LL participants, both evening cortisol levels and recent stressful events increased depression risk, although only the latter remained significant after multivariable adjustment. Conversely, SL individuals appeared somewhat resilient to depression in terms of cortisol and recent stress. These findings indicate that 5-HTTLPR genetic variability appears to influence the association between stress-related factors and late-life depression, although the gene-environment interactions failed to reach statistical significance levels. Participants homozygous for the short allele appeared to have a cortisol-related neuroendocrine vulnerability to depression, while long allele homozygotes were more reactive to stressful events in terms of depression risk.
authors.affiliation: Inserm, U1061, University Montpellier, Montpellier, France. Electronic address: marie-laure.ancelin@inserm.fr.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Ancelin
authors.affiliation: Inserm, U1061, University Montpellier, Montpellier, France.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Scali
authors.affiliation: Inserm, U1061, University Montpellier, Montpellier, France.
authors.forename: Joanna
authors.initials: J
authors.lastname: Norton
authors.affiliation: Inserm, U1061, University Montpellier, Montpellier, France; Center for Clinical Brain Sciences, University of Edinburgh, UK.
authors.forename: Karen
authors.initials: K
authors.lastname: Ritchie
authors.affiliation: Inserm, U1061, University Montpellier, Montpellier, France; Lapeyronie University Hospital, Montpellier, France.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Dupuy
authors.affiliation: Inserm, U1061, University Montpellier, Montpellier, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Chaudieu
authors.affiliation: Inserm, U1061, University Montpellier, Montpellier, France; Disease Epigenetics Group, Murdoch Children's Research Institute, and Department of Paediatrics, The University of Melbourne, Parkville, Australia; Department of Epidemiology and Preventative Medicine, School of Public Health and Preventative Medicine, Monash University, Prahran, Australia.
authors.forename: Joanne
authors.initials: J
authors.lastname: Ryan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D002940:Circadian Rhythm / Q000502:physiology; D003863:Depression / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D003865:Major Depressive Disorder / Q000175:diagnosis* / Q000235:genetics / Q000503:physiopathology; D005260:Female; D059647:Gene-Environment Interaction; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D008016:Life Change Events; D008297:Male; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D012463:Saliva / Q000737:chemistry; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics; D012720:Severity of Illness Index; D013315:Stress, Psychological / Q000235:genetics / Q000503:physiopathology; D063189:Symptom Assessment
chemical_list: D050486:Serotonin Plasma Membrane Transport Proteins; D006854:Hydrocortisone
keywords: Cortisol; Depression; Elderly; Hypothalamic-pituitary-adrenal axis; Serotonin transporter-linked promoter region; Stress