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Introduction The ABCB 1-gene product P-glycoprotein is an efflux pump in the blood-brain-barrier. Different alleles of the single nucleotide polymorphism (SNP) rs2032583 were associated with highly different treatment responses to antidepressants in a retrospective study suggesting a different activity of the P-glycoprotein resulting in different levels of antidepressant in the brain. Objectives/Aims To prospectively test whether escitalopram is associated with a stronger REM-sleep suppression in homozygote or heterozygote cytosine-carriers of that SNP than homozygote thymine-carriers, suggesting higher escitalopram brain levels in cytosine-carriers. Methods 10 male and 10 female healthy, young cytosine-carriers, 20 male and 10 female homozygote thymine-carriers received escitalopram 10mg/day for four days. Prior and after that period, polysomnography was recorded. Results At baseline, sleep in males was worse in cytosine-carriers than homozygote thymine-carriers as indicated, for example, by a significantly longer time awake (cytosine-carriers: 85±15 min; thymine-carriers: 44±6 min). Sleep in females did not differ between groups. In both groups, REM sleep was significantly reduced after treatment but there were no significant differences (cytosine-carriers: 78±5 min (baseline) to 46±4 min; thymine-carriers: 89±4 (baseline) to 49±5 min. All treatment effects of escitalopram on sleep (prolonged REM latency and sleep onset latency, increased non-REM-sleep, stage 2 sleep, stage 4 sleep, reduced REM sleep) did neither depend on sex nor genotype. Conclusions Sleep in males but not in females is relevantly influenced by the alleles of SNP rs2032583 of the ABCB1-gene. However, our hypothesis of a different REM sleep suppression due to different brain levels of escitalopram was not corroborated.

Within the vigilance regulation model the hyperactivity and sensation seeking observed in overtired children, ADHD and mania are interpreted as an autoregulatory attempt to stabilize vigilance (central nervous arousal) by increasing external stimulation. Correspondingly the withdrawal and sensation avoidance in major depression is interpreted as a reaction to a state of tonically high vigilance (1, 2). Using an EEG-based algorithm to classify automatically short EEG-segments into different vigilance stages as observed during the transition from active wakefulness to drowsiness and sleep onset (VIGALL), both patients with ADHD and mania show an unstable vigilance regulation with rapid drops to lower vigilance stages under quiet rest. The contrary was found in unmedicated patients with major depression (2). Studies will be presented supporting the validity of VIGALL (simulataneous EEG-fMRI and EEG/FDG-PET studies, as well as the neurophysiological, clinical and predictive validity of the vigilance regulation model of affective disorders. Among the far reaching consequences of the vigilance model is the question whether psychostimulants have similar beneficial effects in mania as observed in ADHD (3), an aspect which is presently studied in an international, randomized controlled trial (4).

IntroductionGhrelin showed antidepressant-like effects in mice. Furthermore, ghrelin influences sleep and the activity of hypothalamic-pituitary-adrenal (HPA) and somatotropic axis in healthy humans as indicated by increased cortisol and growth hormone (GH) plasma levels. Both sleep and the activity of these endocrine axes are disturbed in depression.ObjectiveTo study the effect of ghrelin on psychopathology, sleep and secretion of cortisol and GH in patients with major depression.MethodsDepressive symptoms as assessed by a validated self rating scale (’Befindlichkeits-Skala’, [well-being scale]), secretion profiles of cortisol and GH and sleep-EEGs were determined in 14 unmedicated patients with major depression (7 women) twice, receiving 50 μg ghrelin or placebo at 2200, 2300, 0000, and 0100 hours.ResultsOverall, depressive symptoms did not change significantly after ghrelin administration (placebo: 37 ± 8; ghrelin: 33 ± 10, p = 0.178). However, there was an improvement at trend level in men (placebo: 36 ± 9 to ghrelin: 30 ± 9, p = 0.093) but not in women. In men, ghrelin was associated with less time awake (placebo: 149.0 ± 11.1; ghrelin: 88.0±12.2 min, p = 0.029) and more non-REM sleep (placebo: 263.2 ± 24.1; ghrelin: 304.9 ± 14.1 min, p = 0.027), in women with less REM sleep (placebo: 108.6 ± 15.7; ghrelin: 74.1 ± 13.8 min, p = 0.031) and longer REM latency (placebo: 49.9 ± 6.5; ghrelin: 85.6 ± 14.1 min, p = 0.019). In both sexes, ghrelin caused strong transient increases of GH and cortisol.ConclusionOur study may provide an initial indication that ghrelin can exert antidepressant effects in patients with major depression. Ghrelin strongly affected sleep and secretion of GH and cortisol in a partly different way as previously reported in healthy subjects.

Sleep studies in patients with major depression receiving the new selective norepinephrine and serotonin reuptake inhibitor (SNRI) duloxetine are lacking. Therefore, polysomnography in 10 patients with major depression (7 males, 39.9+/-7.6 years, HAMD-21 score: 23.6+/-5.6) was recorded twice, before and after 7-14 days of treatment with duloxetine. Stage 3 sleep significantly (P