Melatonin and mental illness

Abstract There have been major advances in knowledge of the role of melatonin in body function and especially in mental illness. Originally isolated as a skin-lightening factor from the pineal gland, it is now known that at physiologic levels it has a key role in the regulation of circadian rhythms. At supraphysiologic levels it has been shown to have neuroprotective as well as cardioprotective effects. In this chapter the authors describe the regulation of melatonin and its relationship to circadian rhythm regulation. They then describe the interaction of melatonin with circadian rhythms and the sleep–wake cycle in major depressive disorder, bipolar depression, and seasonal affective disorder (SAD). An antidepressant has been introduced that represents a new class of antidepressant in that it also acts as an agonist at melatonin receptors and improves several sleep parameters. In seasonal affective disorder bright-light therapy has been shown to be an effective treatment: a treatment that is based on correcting a circadian rhythm misalignment as defined by examining the melatonin rhythm. Sleep–wake alterations in Alzheimer's disease are accompanied by major alterations in melatonin levels and in melatonin receptors in several brain regions. These findings raise the possibility that the melatonin decrease may be important not only for the rhythm disruption but might also have a role in the neurodegeneration itself. In autism spectrum disorders a decrease in melatonin levels along with the final enzyme in the melatonin synthetic pathway has been reported.