title: DHEA metabolism to the neurosteroid androsterone: a possible mechanism of DHEA's antidepressant action.
abstract: BACKGROUND
  Alterations in neurosteroid secretion have been implicated in the efficacy of antidepressants. In a previous study, the adrenal androgen DHEA, a precursor of the neurosteroid androsterone, produced antidepressant and libido-enhancing effects in patients with midlife depression. To investigate the mechanisms underlying DHEA's behavioral effects in this same patient group, we examined plasma levels of four additional neurosteroids implicated in the regulation of affective behavior.
  
  
  METHODS
  Blood samples were assayed for neurosteroids in men (n = 13) and women (n = 10) with midlife depression who previously participated in a crossover study in which DHEA and placebo were administered for 6 weeks each. Depression severity was measured by the Center for Epidemiologic Studies Depression Scale (CES-D). Plasma levels of androsterone (ADT), allopregnanolone, pregnanolone, and pregnenolone were measured by GC-MS at baseline and week 6 of each treatment phase. Data were analyzed with repeated measures analysis of variance (ANOVA-R) and Bonferroni t tests.
  
  
  RESULTS
  ADT levels (but not allopregnanolone, pregnanolone, and pregnenolone) increased after DHEA but not after placebo (F 2,42 = 3.3, p < 0.05). Post-DHEA ADT levels were higher in women than men [t 63 = 2.9, p < 0.05]. However, in both men and women who met criteria for clinical response on the CES-D, baseline ADT levels significantly increased post-DHEA, and the magnitude of the ADT increase post-DHEA treatment was similar in men and women. Consequently, it was the non-responders who accounted for the sex difference in post-DHEA plasma ADT levels, a difference that was driven by values in two women (the only female non-responders).
  
  
  CONCLUSIONS
  The small sample size notwithstanding, these data emphasize the potential behavioral relevance of ADT in humans, which may include contribution to the antidepressant effects of DHEA.
authors.affiliation: Behavioral Endocrinology Branch, National Institute of Mental Health, National Institutes of Health, Public Health Service, Department of Health & Human Services, Building 10, Room 25330, 10 Center Dr MSC 1277, Bethesda, MD, 20892-1277, USA.
authors.forename: Rivka
authors.initials: R
authors.lastname: Ben Dor
authors.forename: Christine E
authors.initials: CE
authors.lastname: Marx
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Shampine
authors.forename: David R
authors.initials: DR
authors.lastname: Rubinow
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Schmidt
mesh_terms: D000738:Androsterone / Q000097:blood*; D000928:Antidepressive Agents / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003687:Dehydroepiandrosterone / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000097:blood / Q000188:drug therapy; D003865:Major Depressive Disorder / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018377:Neurotransmitter Agents / Q000097:blood; D011280:Pregnanolone / Q000097:blood*; D011284:Pregnenolone / Q000097:blood*; D012737:Sex Factors; D016896:Treatment Outcome
chemical_list: D000928:Antidepressive Agents; D018377:Neurotransmitter Agents; D003687:Dehydroepiandrosterone; D011284:Pregnenolone; D011280:Pregnanolone; D000738:Androsterone