Epidemiological studies demonstrate that the incidence of
multiple sclerosis (MS) is age-dependent being rare prior to age 10, unusual prior to age 15, with a peak in the mid 20s. It has been suggested that the manifestation of MS is dependent upon having passed through the pubertal period. In the present communication, I propose that critical changes in pineal
melatonin secretion, which occur in temporal relationship to the onset of puberty, are intimately related to the timing of onset of the clinical manifestations of MS. Specifically, it is suggested that the fall in
melatonin secretion during the prepubertal period, which may disrupt pineal-mediated
immunomodulation, may stimulate either the reactivation of the infective agent or increase the susceptibility to
infection during the pubertal period. Similarly, the rapid fall in
melatonin secretion just prior to delivery may account for the frequent occurrence of relapse in MS patients during the postpartum period. In contrast, pregnancy, which is associated with high
melatonin concentrations, is often accompanied by remission of symptoms. Thus, the presence of high
melatonin levels may provide a protective effect, while a decline in
melatonin secretion may increase the risk for the development and exacerbation of the disease. The
melatonin hypothesis of MS may explain other epidemiological and clinical phenomena associated with the disease such as the low incidence of MS in the black African and American populations, the inverse correlation with sun light and geomagnetic field exposure, the occurrence of relapses in relation to seasonal changes and fluctuations in mood, and the association of MS with affective illness and malignant disease. Therapeutically, this hypothesis implies that application of bright
light therapy or the use of other major synchronizers of circadian rhythms such as
sleep deprivation or application of external weak magnetic fields may be beneficial in the treatment and/or prophylaxis of relapses in the disease.