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 concentrations of 3 alpha-hydroxy-5 alpha-pregnan-20-one (3 Alpha,5 alpha-tetrahydroprogesterone; 3 Alpha,5 alpha-THP), a neuroactive steroid that is a positive allosteric modulator of the GABAA 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 subjects. 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 alpha-THDOC and its precursor 5 alpha-dihydrodeoxycorticosterone (5 alpha-DHDOC) were increased in depressed patients and were not significantly influenced by antidepressant treatment. However, 3 Alpha,5 alpha-THP plasma concentrations were decreased in Depression and clinically effective antidepressant treatment was accompanied by an increase of 3 Alpha,5 alpha-THP concentrations in these patients.

Conclusions: Our results provide the first evidence for a differential alteration in the plasma concentrations of the 3 alpha-reduced neuroactive Steroids 3 Alpha,5 alpha-THDOC and 3 Alpha,5 alpha-THP in major Depression, which is only partially reversed by successful antidepressant treatment.