title: The BDNF Val66Met polymorphism modulates sleep intensity: EEG frequency- and state-specificity.
abstract: OBJECTIVE
  EEG slow waves are the hallmark of deep NREM sleep and may reflect the restorative functions of sleep. Evidence suggests that increased sleep slow waves after sleep deprivation reflect plastic synaptic processes, and that brain-derived neurotrophic factor (BDNF) is causally involved in their homeostatic regulation. The functional Val66Met polymorphism of the gene encoding pro-BDNF causes impaired activity-dependent secretion of mature BDNF protein. We investigated whether this polymorphism contributes to the pronounced inter-individual variation in sleep slow wave activity (SWA) in humans.
  
  
  METHODS
  Sleep laboratory in temporal isolation unit.
  
  
  METHODS
  Eleven heterozygous Met allele carriers and 11 individually sex- and age-matched Val/Val homozygotes.
  
  
  METHODS
  Forty hours prolonged wakefulness.
  
  
  RESULTS
  Cognitive performance, subjective state, and waking and sleep EEG in baseline and after sleep deprivation were studied. Val/Val homozygotes showed better response accuracy than Met allele carriers on a verbal 2-back working memory task. This difference did not reflect genotype-dependent differences in sleepiness, well-being, or sustained attention. In baseline and recovery nights, deep stage 4 sleep and NREM sleep intensity as quantified by EEG SWA (0.75-4.5 Hz) were higher in Val/Val compared to Val/Met genotype. Similar to sleep deprivation, the difference was most pronounced in the first NREM sleep episode. By contrast, increased activity in higher EEG frequencies (> 6 Hz) in wakefulness and REM sleep was distinct from the effects of prolonged wakefulness.
  
  
  CONCLUSIONS
  BDNF contributes to the regulation of sleep slow wave oscillations, suggesting that genetically determined variation in neuronal plasticity modulates NREM sleep intensity in humans.
authors.affiliation: Institute of Pharmacology and Toxicology, University of Zürich, Switzerland.
authors.forename: Valérie
authors.initials: V
authors.lastname: Bachmann
authors.forename: Carina
authors.initials: C
authors.lastname: Klein
authors.forename: Sereina
authors.initials: S
authors.lastname: Bodenmann
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Schäfer
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Berger
authors.forename: Peter
authors.initials: P
authors.lastname: Brugger
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Landolt
mesh_terms: D000328:Adult; D001143:Arousal / Q000235:genetics; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D016022:Case-Control Studies; D004569:Electroencephalography; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008568:Memory / Q000502:physiology; D011110:Polymorphism, Genetic / Q000235:genetics*; D012892:Sleep Deprivation / Q000235:genetics* / Q000503:physiopathology* / Q000523:psychology; D012894:Sleep Stages / Q000235:genetics*; D013997:Time Factors; D055815:Young Adult
chemical_list: D019208:Brain-Derived Neurotrophic Factor