title: DHEAS and cortisol/DHEAS-ratio in recurrent depression: State, or trait predicting 10-year recurrence?
abstract: BACKGROUND
  Major depressive disorder (MDD) has been associated with low dehydroepiandrosterone-sulphate (DHEAS), - particularly relative to high cortisol - although conflicting findings exist. Moreover, it is unclear whether low DHEAS is only present during the depressive state, or manifests as a trait that may reflect vulnerability for recurrence. Therefore, we longitudinally tested whether low DHEAS and high cortisol/DHEAS-ratio in recurrent MDD (I) reflects a trait, and/or (II) varies with depressive state. In addition, we tested associations with (III) previous MDD-episodes, (IV) prospective recurrence, and (V) effects of cognitive therapy.
  
  
  METHODS
  At study-entry, we cross-sectionally compared morning and evening salivary DHEAS and molar cortisol/DHEAS-ratio of 187 remitted recurrent MDD-patients with 72 matched controls. Subsequently, patients participated in an 8-week randomized controlled cognitive therapy trial. We repeated salivary measures after 3 months and 2 years. We measured clinical symptoms during a 10-year follow-up.
  
  
  RESULTS
  Remitted patients showed steeper diurnal DHEAS-decline (p<.005) and a flatter diurnal profile of cortisol/DHEAS-ratio (p<.001) than controls. We found no state-effect in DHEAS or cortisol/DHEAS-ratio throughout follow-up and no association with number of previous episodes. Higher morning cortisol/DHEAS-ratio predicted shorter time till recurrence over the 10-year follow-up in interaction with the effects of cognitive therapy (p<.05). Finally, cognitive therapy did not influence DHEAS or cortisol/DHEAS-ratio.
  
  
  CONCLUSIONS
  Diurnal profiles of DHEAS and cortisol/DHEAS-ratio remain equally altered in between depressive episodes, and may predict future recurrence. This suggests they represent an endophenotypic vulnerability trait rather than a state-effect, which provides a new road to understand recurrent depression and its prevention.
  
  
  BACKGROUND
  www.isrctn.com/ISRCTN68246470.
authors.affiliation: Program for Mood disorders, Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands. Electronic address: R.J.Mocking@amc.uva.nl.
authors.forename: R J T
authors.initials: RJ
authors.lastname: Mocking
authors.affiliation: Program for Mood disorders, Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: C M
authors.initials: CM
authors.lastname: Pellikaan
authors.affiliation: Program for Mood disorders, Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands; Arq Psychotrauma Expert Group, Diemen, The Netherlands.
authors.forename: A
authors.initials: A
authors.lastname: Lok
authors.affiliation: Program for Mood disorders, Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Assies
authors.affiliation: Program for Mood disorders, Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands; University Medical Center Groningen, Program for Mood and Anxiety Disorders, Department of Psychiatry, The Netherlands.
authors.forename: H G
authors.initials: HG
authors.lastname: Ruhé
authors.affiliation: Program for Mood disorders, Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: M W
authors.initials: MW
authors.lastname: Koeter
authors.affiliation: Program for Mood disorders, Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: I
authors.initials: I
authors.lastname: Visser
authors.affiliation: Department of Clinical Psychology, University of Groningen, The Netherlands; Department of Clinical and Health Psychology, Utrecht University, The Netherlands.
authors.forename: C L
authors.initials: CL
authors.lastname: Bockting
authors.affiliation: Arq Psychotrauma Expert Group, Diemen, The Netherlands; Center for Psychological Trauma, Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Olff
authors.affiliation: Program for Mood disorders, Department of Psychiatry, Academic Medical Center, University of Amsterdam, The Netherlands; Department of Psychiatry, Radboud University Medical Center, Nijmegen, The Netherlands; Donders Institute for Brain, Cognition and Behavior, Radboud University, Nijmegen, The Netherlands.
authors.forename: A H
authors.initials: AH
authors.lastname: Schene
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D015928:Cognitive Behavioral Therapy; D003430:Cross-Sectional Studies; D019314:Dehydroepiandrosterone Sulfate / Q000378:metabolism*; D003865:Major Depressive Disorder / Q000378:metabolism* / Q000628:therapy; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000378:metabolism; D011237:Predictive Value of Tests; D012008:Recurrence; D012463:Saliva / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D019314:Dehydroepiandrosterone Sulfate; D006854:Hydrocortisone
keywords: Cortisol; Dehydroepiandrosterone-sulphate (DHEAS); Hypothalamic–pituitary–adrenal (HPA) axis; Major depressive disorder (MDD); Recurrence; Remission