LAUSR

The odds ratio product (ORP), a continuous spectral EEG measure of sleep depth, increases in the transition to adolescence and with psychiatric/behavioral disorders; however, its association with cardiac physiology has been largely unexplored. Heart rate variability (HRV), a continuous spectral EKG measure of cardiac autonomic balance, includes HR oscillations at low frequencies (LF), the standard deviation between normal heart beats or R-R intervals (SDNN) and root mean square of successive differences between normal heartbeats (RMSSD), reflecting sympathetic vs. parasympathetic tone. We aimed to examine the longitudinal association of non-rapid eye movement (NREM) sleep ORP with 24-hour HRV in adolescents. We studied 606 children (Md=9y), of whom 418 were followed-up as adolescents (Md=16y) from the Penn State Child Cohort. We extracted ORP in NREM sleep and in the 9s following cortical arousals (ORP-9) from 9-hour, in-lab polysomnography (PSG), and frequency and time-domain HRV indices from 24-h Holter EKG monitoring immediately following PSG. We stratified 24-h HRV data into daytime and nighttime periods. Linear regression analyses examined the associations between change in ORP and ORP-9 with adolescent 24-h HRV indices, adjusting for age, race, sex, BMI, metabolic syndrome score, AHI, insomnia symptoms, actigraphy-TST, and childhood nighttime HRV indices. While there were no significant associations between ORP and HRV indices in childhood, there were significant longitudinal and cross-sectional associations in adolescence. Longitudinally, a greater increase in ORP since childhood was associated with lower nighttime Log-LF and SDNN in adolescence (both P< 0.05). Similar longitudinal associations were found for ORP-9, with the addition of higher daytime HR and lower daytime SDNN and RMSSD (all P< 0.05). Cross-sectionally, higher ORP and ORP-9 were associated with higher 24-h HR, yet lower Log-LF, SDNN or RMSSD, for both daytime and nighttime periods in adolescence (all P< 0.05). Greater developmental declines in sleep depth and increases in arousability during NREM sleep are associated with impaired cardiac autonomic balance in adolescence, independent of sleep apnea, insomnia or insufficient sleep. These data also suggest a coupling between fine-grain spectral measures of the sleeping brain and those of sympathetic/parasympathetic cardiac modulation, which may inform cardiovascular risk early in life. NIH (R01HL136587, R01MH118308, UL1TR000127)