title: A pilot study of the phase angle between cortisol and melatonin in major depression - a potential biomarker?
abstract: BACKGROUND
  Hypothalamic-pituitary-adrenal (HPA) axis and melatonin rhythm alterations have been independently reported in major depression (MDD) as well as in insomnia. In this pilot study, we link cortisol and melatonin rhythms and propose that the phase angle between cortisol acrophase (CA) and dim-light melatonin onset (20 pg/ml) (DLMO-20) may yield a useful state specific biomarker for MDD.
  
  
  METHODS
  Six healthy (HC) and six depressed (MDD) psychotropic free subjects were admitted to the General Clinical Research Center. Blood was sampled for cortisol and melatonin from 1600h to 1000h, under dim lights (<20lux) and constant routine. Time for DLMO-20 and peak cortisol concentration was determined for each subject. Phase angle was computed as the difference in time between CA and DLMO-20.
  
  
  RESULTS
  Phase angle was significantly increased in MDD's versus HC's (13.40+/-1.61h. versus 11.61+/-1.66h, p=0.026). Using ROC analysis, a phase angle greater than 13.57h distinguished MDD's from HC's (sensitivity=0.83, specificity=1.0). Mean nocturnal melatonin (1600-1000h) was significantly decreased in MDD's versus HC's (22.67+/-9.08 pg/ml versus 47.82+/-14.76 pg/ml, p=0.015).
  
  
  CONCLUSIONS
  The phase angle between CA and DLMO-20 appears to distinguish HC's from MDD's and may be a useful biomarker to aid biologic assessment as well as treatment. Lower nocturnal melatonin in MDD's highlights its importance in MDD's pathophysiology. Additional study with larger sample size is needed to confirm the results of this pilot study. The mechanism for this phase angle difference and decreased melatonin, itself, requires further study.
authors.affiliation: Dept. of Psychiatry and Behavioral Sciences, Stanford University Medical School, 401 Quarry Road, Stanford, CA 94305-5730, United States. tbuckley@stanfordalumni.org
authors.forename: Theresa M
authors.initials: TM
authors.lastname: Buckley
authors.forename: Alan F
authors.initials: AF
authors.lastname: Schatzberg
mesh_terms: D000328:Adult; D002940:Circadian Rhythm; D003430:Cross-Sectional Studies; D003865:Major Depressive Disorder / Q000097:blood*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood*; D008297:Male; D008550:Melatonin / Q000097:blood*; D008875:Middle Aged; D010865:Pilot Projects; D012372:ROC Curve; D013997:Time Factors; D055815:Young Adult
chemical_list: D008550:Melatonin; D006854:Hydrocortisone