title: Low early morning plasma cortisol in posttraumatic stress disorder is associated with co-morbid depression but not with enhanced glucocorticoid feedback inhibition.
abstract: BACKGROUND
  Co-morbid major depressive disorder (MDD) in individuals with posttraumatic stress disorder (PTSD) confers a more severe clinical course and is associated with distinct biologic abnormalities. Although dysregulation in the hypothalamic pituitary adrenal (HPA) axis has been well established in PTSD, the impact of commonly co-occuring MDD has received scant attention.
  
  
  METHODS
  Overnight (7p.m. to 7a.m.) plasma cortisol, adrenocorticotropic hormone (ACTH), dehydroepiandrosterone sulphate (DHEA-S) were measured at 30 min intervals in 9 participants with PTSD with MDD (PTSD+MDD), 9 with PTSD without MDD (PTSD-MDD) and 16 non-traumatized healthy controls. A low-dose dexamethasone suppression test was administered to evaluate feedback sensitivity to glucocorticoids. Linear mixed models with body mass index (BMI) and age as covariates and Bonferroni corrected post hoc tests assessed group differences.
  
  
  RESULTS
  Compared to healthy controls, subjects with PTSD+MDD, but not those subjects with PTSD-MDD, exhibited lower basal plasma cortisol levels between 1:30 a.m. and 3:30 a.m. and at 4:30 a.m. and 6:30 a.m. (effect size d=0.75). Despite similar plasma ACTH levels between the three groups, the ACTH/cortisol ratio was higher in PTSD+MDD patients compared to controls. We obtained similar results when the patient and control groups were re-studied 1 week later, and when men and current smokers were excluded. Basal plasma DHEA-S levels, and cortisol and ACTH response to a low-dose dexamethasone suppression test were similar in all three groups.
  
  
  CONCLUSIONS
  Lower early morning plasma cortisol levels and a high ACTH/cortisol ratio in subjects with PTSD and co-morbid MDD may not be due to enhanced peripheral sensitivity to glucocorticoids. A central abnormality in glucocorticoid regulation could explain HPA axis dysfunction in this subgroup.
authors.affiliation: Mood and Anxiety Disorders Program, National Institute of Mental Health, Bethesda, MD 20892, USA. meena.vythilingam@ha.osd.mil
authors.forename: M
authors.initials: M
authors.lastname: Vythilingam
authors.forename: J M
authors.initials: JM
authors.lastname: Gill
authors.forename: D A
authors.initials: DA
authors.lastname: Luckenbaugh
authors.forename: P W
authors.initials: PW
authors.lastname: Gold
authors.forename: C
authors.initials: C
authors.lastname: Collin
authors.forename: O
authors.initials: O
authors.lastname: Bonne
authors.forename: K
authors.initials: K
authors.lastname: Plumb
authors.forename: E
authors.initials: E
authors.lastname: Polignano
authors.forename: K
authors.initials: K
authors.lastname: West
authors.forename: D
authors.initials: D
authors.lastname: Charney
mesh_terms: D000293:Adolescent; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000328:Adult; D001143:Arousal / Q000502:physiology*; D002940:Circadian Rhythm / Q000502:physiology; D015897:Comorbidity; D003863:Depression / Q000097:blood* / Q000150:complications / Q000453:epidemiology; D004305:Dose-Response Relationship, Drug; D025461:Feedback, Physiological / Q000187:drug effects* / Q000502:physiology; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008297:Male; D008875:Middle Aged; D013313:Stress Disorders, Post-Traumatic / Q000097:blood* / Q000150:complications / Q000453:epidemiology; D015854:Up-Regulation / Q000187:drug effects; D055815:Young Adult
chemical_list: D005938:Glucocorticoids; D000324:Adrenocorticotropic Hormone; D006854:Hydrocortisone