Concentrations of 3 alpha-reduced neuroactive steroids and their precursors in plasma of patients with major depression and after clinical recovery

Background: There is preclinical and clinical evidence that plasma concentr ations of 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 alpha,5 alpha-tetrahydr oprogesterone; 3 alpha,5 alpha-THP), a neuroactive steroid thar is a positi ve allosteric modulator of the GABA(A) receptor, are altered in depression and normalize as a result of antidepressant treatment. However; no data are available on the concentrations of 3 alpha,21-dihydroxy-5 alpha-pregnan-20 -one (3 alpha,5 alpha-tetrahydrodeoxycorticosterone ; 3 alpha,5 alpha-THDOC ), another GABA ergic neuroactive steroid in depression. Methods: We studied nine depressed patients before and after treatment with various antidepressants and compared them to healthy matched control subje cts. Blood samples were quantified by means of a highly sensitive combined gas chromatography/mass spectrometry analysis. Results: Compared to control subjects, plasma concentrations of 3 alpha,5 a lpha-THDOC and its precursor 5 alpha-dihydrodeoxycorticosterone (5 alpha-DH DOC) were increased in depressed patients and were not significantly influe nced by antidepressant treatment. However; 3 alpha,5 alpha-THP plasma conce ntrations were decreased in depression and clinically effective antidepress ant treatment was accompanied by an increase of 3 alpha,5 alpha-THP concent rations in these patients. Conclusions: Our results provide the first evidence for a differential alte ration in the plasma concentrations of the 3 alpha-reduced neuroactive ster oids 3 alpha,5 alpha-THDOC and 3 alpha,5 alpha-THP in major depression, whi ch is only partially reversed by successful antidepressant treatment. Biol Psychiatry 1999;45:274-277 (C) 1999 Society of Biological Psychiatry.