title: Cortisol metabolism in depressed patients and healthy controls.
abstract: BACKGROUND
  Chronic stress as well as major depressive disorders are associated with hypercortisolemia and impaired hypothalamic-pituitary-adrenocortical axis functioning. The aim of this study was to determine whether in major depression changes in the activity patterns of local modulators of glucocorticoid action might contribute to an increase in cortisol bioavailability and if they change during antidepressant treatment and clinical response.
  
  
  METHODS
  Concentrations of urinary total cortisol (UFF), urinary total cortisone (UFE), tetrahydrocortisone (THE), tetrahydrocortisol (THF) and allo-THF (5alpha-THF) were measured in 10-hour nocturnal urine samples of 19 depressed patients and 15 healthy controls. The activity of 11beta-hydroxysteroid dehydrogenases (11beta-HSD) as well as 5alpha- and 5beta-reductases was assessed by calculating the ratios of glucocorticoid metabolites. Patients were treated for 28 days with either mirtazapine or venlafaxine. Enzyme activity was observed during the course of treatment and compared to healthy controls. Responders to treatment were selected for this analysis.
  
  
  RESULTS
  Depressed patients showed reduced 5alpha-reductase activity manifested as a significantly lower amount of 5alpha-THF (102.8 +/- 167.2 vs. 194.6 +/- 165.8 microg, p = 0.019). The increase in the UFF/UFE ratio (0.73 +/- 0.32 vs. 0.29 +/- 0.13, p < 0.0001) indicates reduced activity of renal 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2). During pharmacological treatment, 5alpha-reductase activity in patients returned to the level of the control group, while the decrease in 11beta-HSD2 activity persisted until day 28.
  
  
  CONCLUSIONS
  Our results show changes in activity of intracellular modulators of steroid action in major depressive disorders, particularly a reduced activity of the intracellular cortisol-deactivating enzymes 5alpha-reductase and 11beta-HSD2. These changes suggest an increase in cortisol bioavailability within tissues.
authors.affiliation: Central Institute of Mental Health, J5, Mannheim, Germany. benedikt.roemer@zi-mannheim.de
authors.forename: Benedikt
authors.initials: B
authors.lastname: Römer
authors.forename: Sabina
authors.initials: S
authors.lastname: Lewicka
authors.forename: Daniel
authors.initials: D
authors.lastname: Kopf
authors.forename: Florian
authors.initials: F
authors.lastname: Lederbogen
authors.forename: Bettina
authors.initials: B
authors.lastname: Hamann
authors.forename: Maria
authors.initials: M
authors.lastname: Gilles
authors.forename: Claudia
authors.initials: C
authors.lastname: Schilling
authors.forename: Vera
authors.initials: V
authors.lastname: Onken
authors.forename: Pascal
authors.initials: P
authors.lastname: Frankhauser
authors.forename: Michael
authors.initials: M
authors.lastname: Deuschle
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018687:Antidepressive Agents, Second-Generation / Q000627:therapeutic use; D000929:Antidepressive Agents, Tricyclic / Q000627:therapeutic use; D003348:Cortisone / Q000652:urine; D003511:Cyclohexanols / Q000627:therapeutic use; D003865:Major Depressive Disorder / Q000188:drug therapy / Q000201:enzymology / Q000652:urine*; D005260:Female; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism* / Q000652:urine*; D008803:Mianserin / Q000031:analogs & derivatives / Q000627:therapeutic use; D008875:Middle Aged; D000078785:Mirtazapine; D013760:Tetrahydrocortisol / Q000031:analogs & derivatives / Q000652:urine; D013761:Tetrahydrocortisone / Q000652:urine; D000069470:Venlafaxine Hydrochloride; D055815:Young Adult
chemical_list: D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D003511:Cyclohexanols; D008803:Mianserin; C006461:allotetrahydrocortisol; D013761:Tetrahydrocortisone; D000069470:Venlafaxine Hydrochloride; D013760:Tetrahydrocortisol; D000078785:Mirtazapine; D003348:Cortisone; D006854:Hydrocortisone