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Nocturnal melatonin secretion and polysomnographic sleep patterns were investigated in ten patients with chronic primary insomnia (age 41.3 +/- 9.5 years) and in five healthy subject, (age 27.2 +/- 0.7 years) after either a single intravenous administration of 25 mg doxepin or placebo in a randomized, double blind, and cross-over setting. In the patient group a third session was performed after a three-week open oral treatment with 25 mg doxepin daily. The single-dose administration of doxepin did not affect plasma melatonin concentrations in either the patients on the healthy subjects. After three weeks of oral doxepin intake by the patients, the area under the curve of total nocturnal plasma melatonin concentration was significantly increased by 26% and the peak values were increased by 30%. Both after the single i.v. treatment as well as after long-term oral administration, doxepin also significantly improved sleep latency, total sleep time, and sleep efficiency in the insomniacs as well as the healthy subjects, whereas the nocturnal wake time was decreased. These findings indicate that this tricyclic antidepressant not only improves sleep and but also preserves the secretion of a hormone which is believed to play a special role in the circadian sleep-wake rhythm. Long-term doxepin treatment of chronic insomniac patients not only improves sleep but also restores nocturnal melatonin secretion in these patients.

An initial sample of 120 healthy young men was screened by a personality questionnaire and 15 subjects each with highest and lowest scores respectively on emotionality (emotionally labile, EL subjects and emotionally stable, ES subjects) were recruited for a study on the relationship between the degree of emotionality and the basal secretion of stress-sensitive hormones during nighttime. The nocturnal urinary excretion of cortisol, testosterone, adrenaline, noradrenaline and melatonin was measured over a period of 5 consecutive nights. The average amounts of each hormone excreted per night were not different between the two extreme groups. The variability of the excretion during the 5 nights of cortisol and testosterone, but not of adrenaline, noradrenaline and melatonin, was significantly higher in EL compared to ES subjects. The larger fluctuations in the nocturnal secretion of these two (and no other) hormones in EL subjects indicate that emotional lability is associated with a more labile regulation of cortisol and testosterone secretion. The observed intraindividual variability of basal stress hormone secretion may contribute to the vast interindividual variability noticed in psychoneuroendocrine stress research, especially in emotionally labile subjects.

Persisting alterations in monoaminergic innervation patterns have been observed following various environmental manipulations and neuro-psychopharmacological treatments during fetal or early postnatal life. The present study investigates the question how differences in initial growth conditions at birth might interfere with subsequent development of both serotonergic and noradrenergic innervation in the rat frontal cortex (FC) and brain stem. For this purpose, newborn rat littermates were divided into two groups, a low and a high birth weight group, and the densities of both serotonin (5-HT) and norepinephrine (NE) transporters in the FC and brain stem were analyzed at adulthood. 5-HT transporter density in the FC was significantly higher in the high birth weight group as compared with the low birth weight group. No significant differences were observed between both groups in the density of 5-HT transporters in the brain stem and in the densities of NE transporters in FC and brain stem. It is discussed that differences in birth weight may affect the postnatal development of 5-HT projections to the frontal cortex.