A physiological dose of orally administered melatonin shifts circadian rhythms in humans according to a phase-response curve (PRC) that is nearly opposite in phase with the PRCs for light exposure: melatonin delays circadian rhythms when administered in the morning and advances them when administered in the afternoon or early evening. The human melatonin PRC provides critical information for using melatonin to treat circadian phase sleep and mood disorders, as well as maladaptation to shift work and transmeridional air travel. The human melatonin PRC also provides the strongest evidence to date for a function of endogenous melatonin and its suppression by light in augmenting entrainment of circadian rhythms by the light-dark cycle.

Melatonin shifts human circadian rhythms according to a phase-response curve.

A comparative method of studying the biological bases of personality compares human trait dimensions with likely animal models in terms of genetic determination and common biological correlates. The approach is applied to the trait of sensation seeking, which is defined on the human level by a questionnaire, reports of experience, and observations of behavior, and on the animal level by general activity, behavior in novel situations, and certain types of naturalistic behavior in animal colonies. Moderately high genetic determination has been found for human sensation seeking, and marked strain differences in rodents have been found in open-field behavior that may be related to basic differences in brain neurochemistry. Agonistic and sociable behaviors in both animals and humans and the trait measure of sensation seeking in humans have been related to certain common biological correlates such as gonadal hormones, monoamine oxidase (MAO), and augmenting of the cortical evoked potential.The monoamine systems in the rodent brain are involved in general activity, exploratory behavior, emotionality, socialization, dominance, sexual and consummately behaviors, and intracranial self-stimulation. Preliminary studies have related norepinephrine and enzymes involved in its production and degradation to human sensation seeking. A model is suggested that relates mood, behavioral activity, sociability, and clinical states to activity of the central catecholamine neurotransmitters and to neuroregulators and other transmitters that act in opposite ways on behavior or stabilize activity in the arousal systems. Stimulation and behavioral activity act on the catecholamine systems in a brain–behavior feedback loop. At optimal levels of catecholamine systems activity (CSA) mood is positive and activity and sociability are adaptive. At very low or very high levels of CSA mood is dysphoric, activity is restricted or stereotyped, and the organism is unsocial or aggressively antisocial. Novelty, in the absence of threat, may be rewarding through activation of noradrenergic neurons.

https://www.cambridge.org/core/services/aop-cambridge-core/content/view/S0140525X00018938

Sensation seeking: A comparative approach to a human trait

We examined effects of very low doses of melatonin (0.1-10 mg, orally) or placebo, administered at 1145 h, on sleep latency and duration, mood, performance, oral temperature, and changes in serum melatonin levels in 20 healthy male volunteers. A repeated-measure double-blind Latin square design was used. Subjects completed a battery of tests designed to assess mood and performance between 0930 and 1730 h. The sedative-like effects of melatonin were assessed by a simple sleep test: at 1330 h subjects were asked to hold a positive pressure switch in each hand and to relax with eyes closed while reclining in a quiet darkened room. Latency and duration of switch release, indicators of sleep, were measured. Areas under the time-melatonin concentration curve varied in proportion to the different melatonin doses ingested, and the 0.1- and 0.3-mg doses generated peak serum melatonin levels that were within the normal range of nocturnal melatonin levels in untreated people. All melatonin doses tested significantly increased sleep duration, as well as self-reported sleepiness and fatigue, relative to placebo. Moreover, all of the doses significantly decreased sleep-onset latency, oral temperature, and the number of correct responses on the Wilkinson auditory vigilance task. These data indicate that orally administered melatonin can be a highly potent hypnotic agent; they also suggest that the physiological increase in serum melatonin levels, which occurs around 2100 h daily, may constitute a signal initiating normal sleep onset.

https://www.pnas.org/content/pnas/91/5/1824.full.pdf

Effect of inducing nocturnal serum melatonin concentrations in daytime on sleep, mood, body temperature, and performance

The functional linkage between platelet MAO activity and psychopathology was explored by analyzing temperamental correlates in 40 male subjects by means of scales from the Eysenck Personality Questionnaire (EPQ), the Zuckerman Sensation Seeking Inventory, and the Karolinska Scales of Personality (KSP). Linear correlations were found with two sensation seeking scales, replicating earlier findings. However, nonlinear correlations predominated. Subjects with intermediate platelet MAO activity had higher scores in conformity scales and lower scores in anxiety and hostility scales than low and high MAO subgroups. Low MAO subjects showed a pattern of higher scores in KSP Impulsiveness, EPQ Neuroticism, and KSP Somatic Anxiety and Irritability and lower scores in KSP Socialization, in line with personality profiles found in alcoholics, psychopaths, and suicide attempters who also tend to have low platelet MAO activity. High MAO subjects scored lower in sensation seeking and conformity scales and higher in KSP Psychasthenia, Muscular Tension and Suspicion scales, consistent with clinical links between high platelet MAO activity and anxiety and paranoia.

Markers for vulnerability to psychopathology: Temperament traits associated with platelet MAO activity

In a survey of 541 diabetic males, aged 20–59 years, 190 (35%) had erectile impotence. Using linear logistic regression models for analysis the five most significant associations with impotence were age (p<0.001), treatment with either insulin or oral hypoglycaemic agents (p<0.001), retinopathy (p<0.001), symptomatic peripheral neuropathy (p<0.001) and symptomatic autonomic neuropathy (p<0.005). The greatest correlations were found in patients with severe microangiopathy, as demonstrated by proliferative retinopathy and symptomatic autonomic neuropathy. In addition the duration of diabetes and the presence of ischaemic heart disease, nephropathy and poor diabetic control may also be associated with diabetic impotence. It is concluded that diabetic impotence is still a common problem and may have a multifactorial aetiology.

/pdf/the-prevalence-of-diabetic-impotence-30jtyxyfux.pdf

The prevalence of diabetic impotence.

Platelet monoamine oxidase (MAO) activity and personality characteristics were correlated in a sample of 52 men (37 +/- SD 13 years) and 54 women (37 +/- SD 15 years) from a rural community. Personality characteristics were measured by using the Freiburger Personlichkeitsinventar (FPI-A). In males, weak but significant linear correlations (Pearson product-moment and Spearman rank correlations) were found between platelet MAO activity (p-tyramine and benzylamine as substrates) and the extraversion/introversion dimension. In the females, however, there were no consistent significant correlations between MAO activity and FPI test scores. Comparing the top and bottom 25% of the platelet MAO distribution resulted in a significant difference for the second order factor extraversion in the group of men but not in the group of women. The significant correlation between MAO and introversion could not be attributed to cigarette smoking, food consumption, alcohol, or drugs. In accord with previous biochemical-behavior research, it is suggested that reduced platelet MAO activity may, to some extent, reflect an impulsive personality type.

Correlation of platelet MAO activity with introversion: A study on a German rural population

There is no conclusive evidence supporting an interaction between the pineal gland and the hypothalamic-pituitary-adrenal axis. In this study, 11 healthy adults (six women, five men; aged 18-47 years) received a placebo the first night and 1 mg dexamethasone the next night at either 1800 or 2300 h. Administration of 1 mg of dexamethasone was followed by an attenuation of the nocturnal production of melatonin in 9 of 11 subjects. A significant reduction was found between melatonin plasma levels before and after dexamethasone at 0400 h (P less than 0.01, t test for dependent groups). It is suggested that dexamethasone affects nocturnal production of melatonin by means of mechanisms within the pineal gland.

Influence of dexamethasone on nocturnal melatonin production in healthy adult subjects.

The influence of various antidepressants on the morning levels of plasma melatonin was studied in human volunteers after acute and subchronic administration in weekly increasing doses over a period of three weeks. Two monoamine oxidase (MAO) inhibitors (tranylcypromine: irreversible type A and B; pirlindole: reversible type A), two reuptake inhibitors (maprotiline: selective for noradrenaline; fluvoxamine: selective for serotonin) and an alpha 1/alpha 2-adrenergic and serotonin S2-receptor antagonist (mianserin) were administered to groups of 4 to 7 healthy volunteers each. Two hours after a single oral dose at 9 a.m., at the end of each week and one week after the last dose, morning levels of melatonin were measured using a radioimmunological method. In addition, platelet MAO activity and the uptake of 14C-5-HT into platelets were determined. Plasma melatonin concentrations at 9 a.m. were significantly increased after the intake of 150 mg fluvoxamine the night before; whereas, administration of the same dose in the morning did not lead to increases in melatonin during the day. Following subchronic administration, plasma melatonin levels were significantly increased after the 1st (50 mg/day), 2nd (100 mg/day) and 3rd (150 mg/day) week of fluvoxamine intake in comparison to pre-drug levels. No changes in early morning levels of plasma melatonin were measured in the subjects receiving the other antidepressants, after acute as well as after subchronic administration. The results seem to indicate that following fluvoxamine intake at night, the early morning decline of melatonin is delayed. It is suggested that the underlying mechanism leading to a rise in morning melatonin levels cannot be explained solely on the basis of an inhibition of 5-HT reuptake and that other pharmacological properties of fluvoxamine may be involved.

The influence of acute and subchronic administration of various antidepressants on early morning melatonin plasma levels in healthy subjects: increases following fluvoxamine.

In a double-blind study, melatonin (50 mg) or placebo was administered daily to 25 subjects at 9 am or 7 pm for 1 week. Self-rated fatigue as evaluated by the Stanford Sleepiness Scale (SSS) was significantly increased during the 3 hours following melatonin intake in the morning, whereas, after administration in the evening, no difference between melatonin and placebo could be distinguished. Sleep onset latency slightly decreased in both melatonin groups without reaching statistical significance. No cumulative effects on sleep or behavior were observed. Twelve pituitary and peripheral hormones measured under baseline and partly (in the evening groups) under stimulated conditions before and after the trial did not change. The two most important conclusions are that: 1) the sedative potency of exogenous melatonin depends on the daily time of administration; and 2) the high pharmacological doses used for acute sedation do not seem to have cumulative effects after prolonged application.

Influence of subchronic intake of melatonin at various times of the day on fatigue and hormonal levels: a placebo-controlled, double-blind trial.

A method is described for the determination of unconjugated androstenediol (3β, 17β-dihydroxy-5-androstene) in peripheral plasma based on a competitive protein-binding technique. The procedure includes ether extraction and paper chromatography in the Bush A2 system. Sex steroid binding globulin is derived from patients under estrogen therapy suffering from a carcinoma of the prostate. Separation of bound and unbound androstenediol is carried out by ammonium sulfate precipitation. The precision of the method, evaluated by determining the coefficient of variation of analyses of pools of plasma, was 8.5% for plasma of men and 12.3% for plasma of women. Accuracy was satisfactory, the specificity was proved by mass spectrometry. The mean plasma androstenediol concentration in 19 normal men was 109.9 ± 42.6 (sd) ng/100 ml. In 11 normal women the mean was 61.5 ± 22.7 (sd) ng/100 ml. The difference between male and female values was significant. After stimulation with hCG, plasma androstenediol increased...

K. Demisch

Papers

Correlation of platelet MAO activity with introversion: A study on a German rural population

Influence of dexamethasone on nocturnal melatonin production in healthy adult subjects.

The influence of acute and subchronic administration of various antidepressants on early morning melatonin plasma levels in healthy subjects: increases following fluvoxamine.

Influence of subchronic intake of melatonin at various times of the day on fatigue and hormonal levels: a placebo-controlled, double-blind trial.

Studies about unconjugated androstenediol in human peripheral plasma