title: Angiotensin-converting enzyme gene variants are associated with both cortisol secretion and late-life depression.
abstract: Angiotensin-converting enzyme (ACE) is assumed to influence the activity of the hypothalamic-pituitary-adrenocortical (HPA) axis, which shows hyperactivity in depressed patients. ACE could thus be a promising candidate gene for late-life depression but this has not been examined previously. Depression was assessed in 1005 persons aged at least 65 years, at baseline and over the 10-year follow-up. A clinical level of depression (DEP) was defined as having a score of > or =16 on the Centre for Epidemiology Studies-Depression scale or a diagnosis of current major depression based on the Mini International Neuropsychiatric Interview and according to DSM-IV criteria. Seven single-nucleotide polymorphisms (SNPs) in the ACE gene were genotyped and diurnal cortisol secretion, as an index of HPA axis activity, was measured. Multivariable analyses were adjusted for socio-demographic and vascular factors, cognitive impairment, and apolipoprotein E. Strong significant associations were found between all seven SNPs and DEP and, in particular, first-onset DEP in persons without a past history of depression (P-values ranging from 0.005 to 0.0004). These associations remained significant after correction for multiple testing. The genotypes that were associated with an increased risk of DEP were also significantly associated with an increase in cortisol secretion under stress conditions. Variants of the ACE gene influence cortisol secretion and appear as susceptibility factors for late-life depression in the elderly population. Whether this could represent a common pathophysiological mechanism linking HPA axis and late-life depression remains to be explored.
authors.affiliation: 1] Inserm, U1061, Montpellier, France [2] Univ Montpellier 1, Montpellier, France.
authors.forename: M L
authors.initials: ML
authors.lastname: Ancelin
authors.forename: I
authors.initials: I
authors.lastname: Carrière
authors.forename: J
authors.initials: J
authors.lastname: Scali
authors.forename: K
authors.initials: K
authors.lastname: Ritchie
authors.forename: I
authors.initials: I
authors.lastname: Chaudieu
authors.forename: J
authors.initials: J
authors.lastname: Ryan
mesh_terms: D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D002940:Circadian Rhythm; D003866:Depressive Disorder / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D016015:Logistic Models; D008137:Longitudinal Studies; D008297:Male; D015999:Multivariate Analysis; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D010913:Pituitary-Adrenal System / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies
chemical_list: D007703:Peptidyl-Dipeptidase A; D006854:Hydrocortisone