Pharmacopsychiatry

The process of normal aging is accompanied by changes in sleep- related endocrine activity. During aging, an increase in cortisol at its nadir and a decrease in renin and aldosterone concentration occur. In aged subjects, more time is spent awake and slow-wave sleep is reduced; there is a loss of sleep spindles and accordingly a loss of power in the sigma frequency range. Previous studies could show a close association between sleep architecture, especially slow-wave sleep, and activity in the glutamatergic and GABAergic system. Furthermore, recent studies could show that the natural N-methyl-D-aspartate (NMDA) antagonist and GABA(A) agonist Mg2+ seems to play a key role in the regulation of sleep and endocrine systems such as the HPA system and renin-angiotensin-aldosterone system (RAAS). Therefore, we examined the effect of Mg2+ in 12 elderly subjects (age range 60 - 80 years) on the sleep electroencephalogram (EEG) and nocturnal hormone secretion. A placebo-controlled, randomised crossover design with two treatment intervals of 20 days duration separated by 2 weeks washout was used. Mg2+ was administered as effervescent tablets in a creeping dose of 10 mmol and 20 mmol each for 3 days followed by 30 mmol for 14 days. At the end of each interval, a sleep EEG was recorded from 11 p.m. to 7 a.m. after one accommodation night. Blood samples were taken every 30 min between 8 p.m. and 10 p.m. and every 20 min between 10 p. m. and 7 a.m. to estimate ACTH, cortisol, renin and aldosterone plasma concentrations, and every hour for arginine-vasopressin (AVP) and angiotensin 11 (ATII) plasma concentrations. Mg2+ led to a significant increase in slow wave sleep (16.5 +/- 20.4 min vs. 10.1 +/- 15.4 min, p less than or equal to 0.05), delta power (47128.7 muV(2) +/- 21417.7 muV(2) vs. 37862.1 muV(2) 2 241.7 muV(2), p less than or equal to 0.05) and sigma power (1923.0 muV(2) +/- 1111.3 muV(2)vs. 1541.0 muV(2) +/- 1134.5 muV(2), p less than or equal to 0.05). Renin increased (3.7 +/- 2.3 ng/ml x min vs. 2.3 1.0 ng/ml x min, p < 0.05) during the total night and aldosterone (3.6 +/- 4.7 ng/ml x min vs. 1.1 0.9 ng/ml x min, p < 0.05) in the second half of the night, whereas cortisol (8.3 +/- 2.4 mug/ml x min vs. 11.8 +/- 3.8 mug/ml x min, p < 0.01) decreased significantly and AVP by trend in the first part of the night. ACTH and ATII were not altered. Our results suggest that Mg2+ partially reverses sleep EEG and nocturnal neuroendocrine changes occurring during aging. The similarities of the effect of Mg2+ and that of the related electrolyte Li+ furthermore supports the possible efficacy of Mg2+ as a mood stabiliz