title: Hypothalamic-pituitary-adrenal axis activity in older persons with and without a depressive disorder.
abstract: BACKGROUND
  Altered functioning of the hypothalamic-pituitary-adrenal axis (HPA-axis) has been associated with depression, but findings have been inconsistent. Among older depressed persons, both hyperactivity and hypo-activity of the HPA-axis were demonstrated. However, most studies were population-based studies, with single cortisol measurements, lacking insight into diurnal patterns of HPA-axis functioning. We aim to provide insight into functioning of the HPA-axis, assessed by various salivary cortisol samples, in depressed older adults and non-depressed controls.
  
  
  METHODS
  Data were derived from the Netherlands Study of Depression in Older Persons. Cortisol levels of older persons without a lifetime diagnosis of depression and/or anxiety (n=109) were compared with older persons with a 6-month major depression diagnosis (n=311). ANCOVA analyses and random coefficient analysis on the four morning cortisol samples were performed. A possible U-shaped association between cortisol and depression status was examined.
  
  
  RESULTS
  Depressed older persons showed higher morning cortisol levels at awakening (T1) and a less dynamic awakening response compared to non-depressed older persons. Dexamethasone suppression did not differ across groups. No U-shaped association between HPA-axis activity and depression was observed.
  
  
  CONCLUSIONS
  We demonstrated a hypercortisolemic state and a diminished ability to respond to the stress of awakening among depressed older persons. Previously it was shown, that hypercortisolemic states may indicate a lifelong biological vulnerability for depression. Our findings expand on previous literature by demonstrating that in older persons the HPA-axis may become less responsive to stress, culminating in a further dysregulation of the diurnal cortisol-rhythm, superimposed on - possibly lifelong - hypercortisolemic states.
authors.affiliation: GGZ inGeest/Department of Psychiatry and the EMGO+ Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands. Electronic address: d.rhebergen@ggzingeest.nl.
authors.forename: D
authors.initials: D
authors.lastname: Rhebergen
authors.affiliation: Department of Epidemiology and Biostatistics and the EMGO+ Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: N C M
authors.initials: NC
authors.lastname: Korten
authors.affiliation: GGZ inGeest/Department of Psychiatry and the EMGO+ Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: B W J H
authors.initials: BW
authors.lastname: Penninx
authors.affiliation: GGZ inGeest/Department of Psychiatry and the EMGO+ Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: M L
authors.initials: ML
authors.lastname: Stek
authors.affiliation: Department of Psychiatry, Leiden University Medical Center, The Netherlands.
authors.forename: R C
authors.initials: RC
authors.lastname: van der Mast
authors.affiliation: University Center of Psychiatry & Interdisciplinary Center of Psychiatric Epidemiology, University Medical Center Groningen, The University of Groningen, Groningen, The Netherlands; Department of Psychiatry, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Oude Voshaar
authors.affiliation: GGZ inGeest/Department of Psychiatry and the EMGO+ Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: H C
authors.initials: HC
authors.lastname: Comijs
mesh_terms: D000368:Aged; D002940:Circadian Rhythm / Q000502:physiology*; D003865:Major Depressive Disorder / Q000503:physiopathology*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D012463:Saliva / Q000737:chemistry
chemical_list: D006854:Hydrocortisone
keywords: Cortisol; Depression; HPA-axis; Older persons