title: Defining the boundaries of atypical depression: evidence from the HPA axis supports course of illness distinctions.
abstract: BACKGROUND
  Treatment outcome and brain laterality differ between early onset (<20 years) chronically (no well-being >2 months) depressed patients with atypical features (early/chronic atypical) and those with either later onset or less chronic illness (late/nonchronic atypical). Because hypothalamic-pituitary-adrenal (HPA) axis abnormalities have been hypothesized to distinguish atypical depression from melancholia, we examined whether HPA measures would also differentiate these two groups of depressed patients with atypical features.
  
  
  METHODS
  Three-hour afternoon cortisol levels, stimulation of cortisol by afternoon dextroamphetamine, and suppression of cortisol by dexamethasone were investigated in 85 depressed patients with atypical features. The latter group was divided into early/chronic atypical and late/nonchronic atypical based on chart review of course of illness.
  
  
  RESULTS
  Patients with early/chronic atypical had significantly lower mean 3 h afternoon cortisol levels (N=21) and 4:00 p.m. post-dexamethasone cortisol levels (N=20) than did those with late/nonchronic atypical (N=43 with afternoon cortisol; N=26 with post-dexamethasone cortisol). Post-dextroamphetamine cortisol levels were numerically higher in the early/chronic atypical group (N=15 vs. 19), but this failed to reach conventional significance (0.05<p<0.1). Arbitrary categorical distinctions of normal and abnormal did not separate these groups on any of the tests.
  
  
  CONCLUSIONS
  Lack of demonstrated reliability of the chart review and retrospective determination of atypical features and course of illness limit the generalizability of these findings.
  
  
  CONCLUSIONS
  These HPA data are consistent with earlier treatment and brain laterality findings that course of illness distinguishes biologically distinct groups within depressed patients with atypical features. The DSM should consider adding course of illness requirements to its criteria for atypical features.
authors.affiliation: New York State Psychiatric Institute, United States; Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA. jws6@columbia.edu
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Stewart
authors.forename: Frederic M
authors.initials: FM
authors.lastname: Quitkin
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: McGrath
authors.forename: Donald F
authors.initials: DF
authors.lastname: Klein
mesh_terms: D000328:Adult; D017668:Age of Onset; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology; D015897:Comorbidity; D003866:Depressive Disorder / Q000097:blood / Q000175:diagnosis* / Q000503:physiopathology; D003907:Dexamethasone / Q000494:pharmacology; D003913:Dextroamphetamine / Q000494:pharmacology; D003937:Diagnosis, Differential; D039721:Diagnostic and Statistical Manual of Mental Disorders; D019263:Dysthymic Disorder / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000097:blood* / Q000502:physiology; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D008297:Male; D001523:Mental Disorders / Q000175:diagnosis / Q000453:epidemiology; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D011569:Psychiatric Status Rating Scales / Q000706:statistics & numerical data
chemical_list: D003907:Dexamethasone; D003913:Dextroamphetamine; D006854:Hydrocortisone