Abstract
Specific, sensitive and direct RIAs for the measurement of melatonin and its major urinary metabolite, aMT6s have been developed and applied to investigations of the effects of depression, anorexia nervosa and antidepressant drug treatment upon melatonin secretion.A normal range of melatonin levels was defined from 24-hour plasma melatonin profiles collected from 81 healthy volunteers. In clinical studies controlled for the variables known to affect melatonin secretion, neither the amplitude nor timing of the melatonin rhythm was altered in endogenous (unipolar) depressed patients, whereas patients with seasonal affective disorder displayed elevated morning melatonin levels and greater interindividual variation in the timing and duration of melatonin secretion. Only in patients with anorexia nervosa were changes in amplitude of the melatonin rhythm observed. Increased nocturnal plasma melatonin and urinary aMT6s excretion were found in anorectics compared to healthy women of either normal or low body weight.The noradrenergic control of melatonin secretion in man was demonstrated by an acute stimulation of evening melatonin and aMT6s production in normal volunteers following treatment with specific noradrenaline uptake inhibitors, DMI and oxaprotiline. Furthermore, the administration of rolipram, a phosphodiesterase inhibitor, increased night-time urinary aMT6s excretion in normal subjects, suggesting that cyclic AMP may influence the production of melatonin in man.The role of the pineal as an index of β-adrenergic function was investigated. Chronic (3 weeks) DMI treatment stimulated nocturnal melatonin secretion in depressed patients although melatonin levels in normal subjects were no different from pretreatment values. In addition, repeated DMI injections (22 days) increased day- and night-time rat pineal melatonin concentrations in conjunction with a decrease in pineal and cortical β-adrenoceptor density. Contrary to some popular theories of antidepressant drug action our findings do not provide evidence for reduced noradrenergic neurotransmission during DMI therapy.Plasma melatonin and urinary aMT6s provide unique markers in psychiatric studies for rhythm disturbances and the effects of antidepressant drugs. It appears from the present studies that melatonin production, at least in the rat, is not a good index of antidepressant-induced changes in β-adrenergic receptors. Melatonin production probably reflects the functional status of the noradrenergic synapse in the pineal gland. Whether it has any relevance to central noradrenergic activity is open to question.