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Individual differences in a clock gene predict decline of performance during sleep deprivation

March 09, 2007

People are known to differ markedly in their response to sleep deprivation, but the biological underpinnings of these differences have remained difficult to identify. Researchers have now found that a genetic difference in a so-called clock gene, PERIOD3, makes some people particularly sensitive to the effects of sleep deprivation. The findings, reported by Antoine Viola, Derk-Jan Dijk, and colleagues at the University of Surrey's Sleep Research Center, appear online this week in the journal Current Biology, published by Cell Press.

There are two variants of the PERIOD3 gene found in the human population, encoding either long or short versions of the corresponding protein. Each individual will possess two copies of the gene, either of which might be the long or short form. Previous work had indicated that the different forms of the gene appear to influence characteristic morning and evening activity levels—for example, "owl" versus "lark" tendencies.

In the new work, a multidisciplinary research team consisting of biological scientists and psychologists compared how individuals possessing only the longer gene variant and those possessing only the shorter one coped with being kept awake for two days, including the intervening night. The researchers found that although some participants struggled to stay awake, others experienced no problems with the task.

The results were most pronounced during the early hours of the morning (between 4 and 8 a.m.), during which individuals with the longer variant of the gene performed very poorly on tests for attention and working memory.

The authors point out that this early-morning period corresponds to stretches of time when shift workers struggle to stay awake, during which many accidents related to sleepiness occur. But the scientists also emphasize that the new research was conducted in the laboratory, and whether forms of the PERIOD3 gene also predict individual differences in the tolerance to night-shift work remains to be demonstrated.

An additional finding was that the effects of this gene on performance may be mediated by its effects on sleep. When the volunteers were allowed to sleep normally, those possessing only the longer form of the gene spent about 50% more of their time in slow-wave sleep, the deepest form of sleep. Slow-wave sleep is a marker of sleep need, and it is known that carrying a sleep debt makes it very difficult to stay awake and perform at night.

The findings highlight a possible role for clock genes in human sleep physiology and structure, and the influence these genes might have on performance by unrested individuals.

Cell Press