title: Chronobiological hypothalamic-pituitary-thyroid axis status and antidepressant outcome in major depression.
abstract: BACKGROUND
  We previously demonstrated that the difference between 2300h and 0800h TSH response to protirelin (TRH) tests on the same day (ΔΔTSH test) is an improved measure in detecting hypothalamic-pituitary-thyroid (HPT) axis dysregulation in depression. This chronobiological index (1) is reduced in about three quarters of major depressed inpatients, and (2) is normalized after successful antidepressant treatment. In the present study, we examined whether early changes in HPT axis activity during the first 2 weeks of antidepressant treatment could be associated with subsequent outcome.
  
  
  METHODS
  The ΔΔTSH test was performed in 50 drug-free DSM-IV euthyroid major depressed inpatients and 50 hospitalized controls. After 2 weeks of antidepressant treatment the ΔΔTSH test was repeated in all inpatients. Antidepressant response was evaluated after 6 weeks of treatment.
  
  
  RESULTS
  At baseline, ΔΔTSH values were significantly lower in patients compared to controls and 38 patients (76%) showed reduced ΔΔTSH values (i.e., <2.5mU/L). After 2 weeks of antidepressant treatment, 20 patients showed ΔΔTSH normalization (among them 18 were subsequent remitters), while 18 patients did not normalize their ΔΔTSH (among them 15 were non-remitters) (p<0.00001). Among the 12 patients who had normal ΔΔTSH values at baseline, 8 out 9 who had still normal values after 2 weeks of treatment were remitters, while the 3 with worsening HPT axis function (i.e., reduced ΔΔTSH value after 2 weeks of treatment) were non-remitters (p<0.02). A logistic regression analysis revealed that ΔΔTSH levels after 2 weeks of treatment could predict the probability of remission (odds ratio [OR]=2.11, 95% confidence interval [CI]=1.31-3.41).
  
  
  CONCLUSIONS
  Our results suggest that after 2 weeks of antidepressant treatment: (1) chronobiological restoration of the HPT axis activity precedes clinical remission, and (2) alteration of the HPT axis is associated with treatment resistance.
authors.affiliation: Centre Hospitalier, Pole 8/9, Rouffach, France. Electronic address: f.duval@ch-rouffach.fr.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Duval
authors.affiliation: Centre Hospitalier, Pole 8/9, Rouffach, France.
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Mokrani
authors.affiliation: Centre Hospitalier, Pole 8/9, Rouffach, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Erb
authors.affiliation: Centre Hospitalier, Pole 8/9, Rouffach, France.
authors.forename: Felix
authors.initials: F
authors.lastname: Gonzalez Lopera
authors.affiliation: Centre Hospitalier, Pole 8/9, Rouffach, France.
authors.forename: Claudia
authors.initials: C
authors.lastname: Alexa
authors.affiliation: Centre Hospitalier, Pole 8/9, Rouffach, France.
authors.forename: Xenia
authors.initials: X
authors.lastname: Proudnikova
authors.affiliation: Centre Hospitalier, Pole 8/9, Rouffach, France.
authors.forename: Iuliana
authors.initials: I
authors.lastname: Butucaru
mesh_terms: D000328:Adult; D000928:Antidepressive Agents / Q000008:administration & dosage*; D016022:Case-Control Studies; D002909:Chronobiology Phenomena / Q000187:drug effects; D003865:Major Depressive Disorder / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010913:Pituitary-Adrenal System / Q000187:drug effects* / Q000378:metabolism; D011237:Predictive Value of Tests; D013972:Thyrotropin / Q000097:blood / Q000378:metabolism; D013973:Thyrotropin-Releasing Hormone / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D013973:Thyrotropin-Releasing Hormone; D013972:Thyrotropin
keywords: Antidepressant treatment outcome; Depression; Hypothalamic–pituitary–thyroid (HPT) axis; Thyroid hormones; Thyrotropin (TSH); Thyrotropin-releasing hormone (TRH) test