Naturally occurring benzodiazepines may codetermine chronotypes

Determinants of individual differences in sleep-wake cycles and vigilance are being recognized as major factors of influence in both physical and mental health. Alterations of an accustomed circadian sleep-wake rhythm are commonly seen in the early stages of the majority of psychiatric disorders and, by themselves, predispose to significant morbidity even in the absence of an underlying illness. While it is well known that disruptions of sleep respond favourably to benzodiazepines, agents which have been prescribed for insomnia since their industrial synthesis in the early 1960s, little attention has been paid to putative central nervous system effects of naturally occurring benzodiazepines. These molecules were found in various nutritive plants and have been quantified in human brain and peripheral blood of drug-naive individuals at trace amounts. There is agreement that elevated concentrations of naturally occurring benzodiazepines participate in the complex pathophysiology of hepatic encephalopathy, a condition asssociated with progressive impairment of consciousness and, ultimately, coma. In the present study, we address the relationship between naturally occurring benzodiazepines and time-of-day effects on the behavior of healthy subjects.