Early morning executive functioning during sleep deprivation is compromised by a PERIOD3 polymorphism.
OBJECTIVE
To contrast the effects of total sleep deprivation (TSD) on executive and non-executive function in volunteers homozygous for either the short or long variant of a variable number tandem repeat polymorphism in PERIODS, which is a genetic marker for susceptibility to the negative effect of sleep loss on waking performance.


METHODS
Following two laboratory nights of baseline sleep, both groups underwent an approximately 40-hour constant routine, performing brief tests of executive, memory, attention, and motor function every 2 hours.


METHODS
Clinical Research Centre.


METHODS
Fourteen PER3(4/4) (homozygotes for shorter variant of the gene) and 10 PER3(5/5) (homozygotes for longer variant) healthy, young adults (mean 25.0 +/- 1.0 years).


METHODS
Total sleep deprivation (approximately 40 hours) following baseline sleep.


RESULTS
Hormonal assays established that melatonin levels, which reflect circadian phase, reached their midpoint around 04:00 in both genotypes. Cognitive performance deteriorated across the night, and was similar for both genotypes throughout, except 2-4 h after the midpoint of the melatonin rhythm. Only at this time-point and only on tests of executive function (e.g., 3-back, paced visual serial addition task) did PER3(5/5) participants perform reliably worse. Covariance analyses controlling for genotype dependent differences in homeostatic sleep pressure derived from principal component analysis of baseline sleep latency, slow wave sleep and wake after sleep onset largely removed these early morning differences in executive function.


CONCLUSIONS
This PER3 polymorphism differentially influences the effects of sleep deprivation on executive and non-executive function in the early morning. These effects appear to be mediated through homeostatic sleep pressure.
Groeger
John A
JA
Surrey Sleep Research Centre, Guildford, UK. j.groeger@surrey.ac.uk
Viola
Antoine U
AU
Lo
June C Y
JC
von Schantz
Malcolm
M
Archer
Simon N
SN
Dijk
Derk-Jan
DJ
D000328:Adult; D001143:Arousal / Q000235:genetics*; D001288:Attention / Q000502:physiology*; D002940:Circadian Rhythm / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D006706:Homeostasis / Q000235:genetics; D006720:Homozygote; D006801:Humans; D008297:Male; D008550:Melatonin / Q000097:blood; D011939:Mental Recall / Q000502:physiology*; D018598:Minisatellite Repeats / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D056950:Period Circadian Proteins; D011110:Polymorphism, Genetic / Q000235:genetics*; D011340:Problem Solving / Q000502:physiology*; D011597:Psychomotor Performance / Q000502:physiology*; D012892:Sleep Deprivation / Q000235:genetics* / Q000523:psychology; D014157:Transcription Factors / Q000235:genetics*; D055815:Young Adult
D005819:Genetic Markers; D009687:Nuclear Proteins; C512644:PER3 protein, human; D056950:Period Circadian Proteins; D014157:Transcription Factors; D008550:Melatonin