title: Increased cortisol awakening response was associated with time to recurrence of major depressive disorder.
abstract: BACKGROUND
  Although HPA-axis activity has been studied extensively in relation to depression, there is no consensus whether HPA-axis parameters predicts major depressive disorder (MDD) recurrence. We investigated whether HPA-axis parameters (cortisol awakening response (CAR), the dexamethasone suppression test (DST) and evening cortisol) predict time to recurrence in remitted subjects with a history of MDD and whether childhood trauma and life events interact with HPA-axis parameters in increasing the risk for recurrence.
  
  
  METHODS
  Data were derived from 549 subjects with a lifetime diagnosis of MDD in remission for at least six months preceding the baseline assessment of the Netherlands Study of Depression and Anxiety (NESDA). Subjects were followed up with two interviews over the course of four years to assess recurrence. DSM-IV based diagnostic interviews were used to assess time to recurrence of MDD. Seven salivary cortisol samples collected at baseline with information on CAR, evening cortisol and the DST. Hazard ratios were calculated using Cox regression analysis, adjusted for covariates.
  
  
  RESULTS
  A higher CAR was associated with time to recurrence of MDD (HR=1.03, 95%CI 1.003-1.060, p=0.03) whereas evening cortisol and DST were not. No interactions between HPA-axis parameters and stress-related factors were found.
  
  
  CONCLUSIONS
  Our data support previous studies reporting that subjects with a higher CAR are more vulnerable to recurrence of MDD.
authors.affiliation: Pro Persona, Institute for Mental Health Care, P.O. Box 70, 6710 RR Ede, The Netherlands. Electronic address: f.hardeveld@propersona.nl.
authors.forename: Florian
authors.initials: F
authors.lastname: Hardeveld
authors.affiliation: Pro Persona, Institute for Mental Health Care, P.O. Box 70, 6710 RR Ede, The Netherlands; Netherlands Institute of Mental Health and Addiction, P.O. Box 725, 3500 AS Utrecht, The Netherlands; Behavioral Science Institute, Radboud University Nijmegen, P.O. Box 9104, 6500 HE Nijmegen, The Netherlands.
authors.forename: Jan
authors.initials: J
authors.lastname: Spijker
authors.affiliation: Department of Psychiatry/EMGO Institute for Health and Care/Neuroscience Campus Amsterdam, VU University Medical Center Amsterdam, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands.
authors.forename: Sophie A
authors.initials: SA
authors.lastname: Vreeburg
authors.affiliation: Netherlands Institute of Mental Health and Addiction, P.O. Box 725, 3500 AS Utrecht, The Netherlands.
authors.forename: Ron De
authors.initials: RD
authors.lastname: Graaf
authors.affiliation: Pro Persona, Institute for Mental Health Care, P.O. Box 70, 6710 RR Ede, The Netherlands.
authors.forename: Sanne M
authors.initials: SM
authors.lastname: Hendriks
authors.affiliation: Department of Psychiatry/EMGO Institute for Health and Care/Neuroscience Campus Amsterdam, VU University Medical Center Amsterdam, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands.
authors.forename: Carmilla M M
authors.initials: CM
authors.lastname: Licht
authors.affiliation: Department of Psychiatry, University Medical Center Groningen, University of Groningen, P.O. Box 72, 9700 AB Groningen, The Netherlands.
authors.forename: Willem A
authors.initials: WA
authors.lastname: Nolen
authors.affiliation: Department of Psychiatry/EMGO Institute for Health and Care/Neuroscience Campus Amsterdam, VU University Medical Center Amsterdam, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands.
authors.forename: Brenda W J H
authors.initials: BW
authors.lastname: Penninx
authors.affiliation: Department of Psychiatry/EMGO Institute for Health and Care/Neuroscience Campus Amsterdam, VU University Medical Center Amsterdam, P.O. Box 7057, 1007 MB Amsterdam, The Netherlands.
authors.forename: Aartjan T F
authors.initials: AT
authors.lastname: Beekman
mesh_terms: D000328:Adult; D002940:Circadian Rhythm / Q000502:physiology*; D003865:Major Depressive Disorder / Q000175:diagnosis* / Q000503:physiopathology; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000032:analysis*; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000503:physiopathology*; D012008:Recurrence; D012463:Saliva / Q000737:chemistry; D013997:Time Factors; D014851:Wakefulness / Q000502:physiology
chemical_list: D006854:Hydrocortisone
keywords: HPA axis recurrence major depressive disorder