BDNF VAL66MET polymorphism impacts alertness and performance in shift workers

Introduction: Night shift work typically occurs under conditions of circadian misalignment and sleep restriction, resulting in impaired performance and alertness. There is inter-individual variability in the degree of impairment consequent to shift work, though little is known about the genetic factors that confer resistance or vulnerability. Brain Derived Neurotrophic Factor (BDNF) is a potent modulator of sleep-wake homeostasis and contains a common functional polymorphism in its pro-domain (val66met). The present study examined whether the val66met polymorphism explained inter-individual variability in shift work tolerance as measured by the psychomotor vigilance task (PVT) and electroencephalographic (EEG) correlates of alertness. Methods: Forty-eight night shift workers completed an in-laboratory, simulated night shift and were genotyped for the val66met polymorphism (TaqMan assay; rs6265). Participants completed the auditory PVT and the Karolinska Drowsiness Test (KDT) during the shift. Results: Genotyping of val66met identified 27 val/val homozygotes (19 males; age 32.5±9.5) and 21 met allele carriers (12 males; age 31.3±9.0). Both mean reaction time and attentional lapses increased as a function of time into the simulated night shift, reflecting a general worsening of performance (both p<0.001). The val66met polymorphism moderated this effect such that met allele carriers showed larger increases in mean reaction time and attentional lapses across the night shift, relative to the val homozygotes (both p<0.05). EEG power spectrum analysis revealed a three-way interaction between val66met genotype, time into shift and EEG frequency (p<0.001). Relative to baseline, met-carriers show greater elevation in delta (0.5–4.5Hz) power and a greater reduction in alpha (8.5–12.5Hz) and beta (20- 30Hz) power at the end of shift, compared to val homozygotes (all p<0.001). Conclusion: Our results demonstrate a heightened vulnerability to the effects of shift work among met allele carriers, relative to val homozygotes. The ability to predict an individual’s vulnerability to shift work from genetic data may be utilised in the targeting of those who would benefit most from alertness impairment countermeasures. Support (If Any): Australian National Health and Medical Research Council (NHMRC) Project Grant: 545871.