Neuroactive steroids in responders and nonresponders to sleep deprivation

Evidence from preclinical and clinical studies indicates that concentrations of neuroactive steroids are altered in depression and normalize after antidepressant pharmacotherapy. However, data on the impact of sleep deprivation on concentrations of neuroactive steroids are not available. Therefore, 29 drug-free patients (12 men, 17 women) with 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 6-item version of the Hamilton Depression Scale (6-HAMD). Plasma samples were taken the day before and the day after PSD (day 0 and 1) and after one night of recovery sleep (day 2) at 8:00 AM. Samples were quantified for neuroactive steroids by means of a highly sensitive and specific combined gas chromatography/mass spectrometry analysis. PSD did not influence concentrations of neuroactive steroids in either PSD responders (n = 20) or nonresponders (n = 9). However, nonresponders showed significantly higher concentrations of 3 alpha,5 alpha-tetrahydroprogesterone, 3 alpha,5 beta-tetrahydroprogesterone, and dehydroepiandrosterone 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 in either responders or nonresponders.