Sex differences in the circadian regulation of sleep and waking cognition in humans
Significance Circadian rhythms affect our physiology and psychology, in health and disease. Most of our knowledge about the human circadian timing system is based on research in men. Some circadian characteristics, such as the intrinsic frequency of the circadian clock and the amplitude of the melatonin rhythm, have been shown to differ between men and women. Whether the circadian regulation of mental functions differs between men and women is unknown. Here we show that circadian rhythmicity in mental functions exhibits sex differences so that the night time impairment in cognitive performance is greater in women than in men. These findings are significant in view of shift work related cognitive deficits and disturbances of mood, which are more prevalent in women. The sleep wake cycle and circadian rhythmicity both contribute to brain function, but whether this contribution differs between men and women and how it varies across cognitive domains and subjective dimensions has not been established. We examined the circadian and sleep wake dependent regulation of cognition in 16 men and 18 women in a forced desynchrony protocol and quantified the separate contributions of circadian phase, prior sleep, and elapsed time awake on cognition and sleep. The largest circadian effects were observed for reported sleepiness, mood, and reported effort; the effects on working memory and temporal processing were smaller. Although these effects were seen in both men and women, there were quantitative differences. The amplitude of the circadian modulation was larger in women in 11 of 39 performance measures so that their performance was more impaired in the early morning hours. Principal components analysis of the performance measures yielded three factors, accuracy, effort, and speed, which reflect core performance characteristics in a range of cognitive tasks and therefore are likely to be important for everyday performance. The largest circadian modulation was observed for effort, whereas accuracy exhibited the largest sex difference in circadian modulation. The sex differences in the circadian modulation of cognition could not be explained by sex differences in the circadian amplitude of plasma melatonin and electroencephalographic slow wave activity. These data establish the impact of circadian rhythmicity and sex on waking cognition and have implications for understanding the regulation of brain function, cognition, and affect in shift work, jetlag, and aging.
Proceedings of the National Academy of Sciences