The degree of radiation-induced DNA strand breaks is altered by acute sleep deprivation and psychological stress and is associated with cognitive performance in humans

Study Objectives: Sleep deprivation is associated with impaired immune responses, cancer, and morbidity and mortality, and can degrade cognitive performance, although individual differences exist in such responses. Sleep deprivation induces DNA strand breaks and DNA base oxidation in animals, and psychological stress is associated with increased DNA damage in humans. It remains unknown whether sleep deprivation or psychological stress in humans affects DNA damage response from environmental stressors, and whether these responses predict cognitive performance during sleep deprivation. Methods: Sixteen healthy adults (ages 29-52 years; mean age +/- SD, 36.4 +/- 7.1 years; seven women) participated in a 5-day experiment involving two 8 hr time-in-bed (TIB) baseline nights, followed by 39 hr total sleep deprivation (TSD), and two 8-10 hr TIB recovery nights. A modified Trier Social Stress Test was conducted on the day after TSD. The Psychomotor Vigilance Test measured behavioral attention. DNA damage was assessed in blood cells collected at 5 time points, and blood cells were irradiated ex vivo. Results: TSD, alone or in combination with psychological stress, did not induce significant increases in DNA damage. By contrast, radiation-induced DNA damage decreased significantly in response to TSD, but increased back to baseline when combined with psychological stress. Cognitively vulnerable individuals had more radiation-induced DNA strand breaks before TSD, indicating their greater sensitivity to DNA damage from environmental stressors. Conclusions: Our results provide novel insights into the molecular consequences of sleep deprivation, psychological stress, and performance vulnerability. They are important for fields involving sleep loss, radiation exposure, and cognitive deficits, including cancer therapy, environmental toxicology, and space medicine. Statement of Significance Although sleep loss, by itself or in combination with psychological stress, does not increase DNA damage in human blood cells, DNA strand break levels from ex vivo cell irradiation are lower than baseline when participants are sleep deprived, and increase back to baseline levels when participants are sleep deprived and psychologically stressed. The level of radiation-induced DNA strand breaks is higher in the cells of individuals who are cognitively vulnerable to sleep loss, indicating that they are more sensitive to cellular DNA damage from environmental stressors. These results provide novel insights into the molecular processes induced by sleep deprivation, psychological stress, and cognitive performance deficits, and are significant for identifying biomarkers to predict vulnerability to sleep deprivation and for developing effective countermeasures.