Influence of sleep deprivation on neuroactive steroids in major depression

There is evidence from preclinical and clinical studies that concentrations of neuroactive steroids are altered in depression and normalize after antidepressant pharmacotherapy. However, no data are available concerning the impact of sleep deprivation on the concentrations of neuroactive steroids. A total of 29 drug-free patients (12 men, 17 women) suffering from major depression according to DSM-IV criteria were treated with partial sleep deprivation (PSD). Response to PSD was defined as a reduction of at least 30% according to the six-item version of the Hamilton depression scale (6-HAMD). Plasma samples were taken the day before and after PSD (days 0 and 1) and after one night of recovery sleep (day 2) at 8:00 am. The samples were quantified for neuroactive steroids by means of a highly sensitive and specific combined gas chromatography/mass spectrometry analysis. There was no influence of PSD on the concentrations of neuroactive steroids either in PSD responders (n=20) or in nonresponders (n=9). However, nonresponders showed significantly higher concentrations of 3alpha,5alpha-tetrahydroprogesterone (3alpha,5alpha-THP), 3alpha,5beta-tetrahydroprogesterone (3alpha,5beta-THP), and dehydroepiandrosterone (DHEA) before or after PSD compared to responders. In contrast to antidepressant drugs, which correct the dysequilibrium of neuroactive steroids in major depression within several weeks, PSD does not affect the concentrations of neuroactive steroids either in responders or in nonresponders.