Sleep and Inflammation During Adolescence

This article is authored by Brandon Williams and Danny Rahal and is part of the 2020 pre-graduate spotlight week. 

Adolescence is a period marked by significant biological and social changes, including pubertal changes and greater responsibility. In turn, many adolescents struggle to maintain a regular sleep schedule and do not get the recommended 8 to 10 hours of sleep per night (1). Whether it be due to trouble falling asleep, staying awake to study for a test, or scrolling through social media, many teenagers are losing out on their precious nighttime sleep. These deficits in sleep duration and quality can lead to social and behavioral issues. For example, high school students who sleep less often have decreased academic performance, as they had more trouble processing material and were more likely to struggle with an assignment (2-3). Moreover, lower grades in school may suggest poorer study habits. Students who are behind in school may turn to more late-night study sessions, further disrupting and worsening their sleep. There is no doubt that a sleepless night will leave you feeling tired the next day. However, in addition to mental health, can lower sleep duration affect biological markers of physical health? Recent research shows that an accumulation of sleepless nights may actually have adverse effects on health outcomes as early as during adolescence. 

One health outcome of interest is inflammation— the body’s natural response to injury to illness or injury. Have you ever had a rash that was swollen, red, and warm to the touch? If so, then you have first-hand experience with inflammation. This bodily response is unique in that high levels of inflammation are a risk factor for the development of chronic health issues—namely cardiovascular disease (CVD; 4-6). Interestingly, levels of inflammation also appear sensitive to changes in sleep behaviors. A reliable measure for inflammation throughout the body is the biomarker C-reactive protein (CRP). Increased levels of CRP in the blood predict the development of CVD, and clinical cutoffs have been established for physicians to implement health care treatment plans. CRP concentrations lower than 1.0 mg/L are categorized as low risk, 1.0 to 3.0 mg/L as intermediate risk, and greater than 3.0 mg/L as high risk for CVD in Western society (7). Teenagers usually do not develop any symptoms of CVD until adulthood, but progression of this disease is a lifelong process. High levels of CRP in early childhood could result in premature cardiovascular health issues—such as heart attack or stroke.

Researchers have spent a lot of time looking at both objective and subjective measures of sleep, trying to pinpoint which aspects of sleep relate to inflammation. Measures of subjective sleep assess how rested you feel and how well you believe you slept. Subjective sleep data are usually obtained through surveys or questionnaires. In contrast, measures of objective sleep assess how long you were physically asleep, as well as any variability in sleep patterns throughout a span of time. To measure objective sleep, researchers need to track participants’ activity using actigraphy. Actigraphy refers to the measure of people’s activity, which is especially helpful in sleep research because researchers can collect data regarding when participants go to bed, wake up, toss and turn in bed and get up to use the restroom.  In two different studies, researchers used actigraphy watches to measure objective sleep and found that shorter sleep duration is associated with higher levels of the inflammatory biomarker CRP in adolescents (6, 8). In adults, however, it seems that poor subjective sleep—rather than objective sleep— is more robustly associated with inflammation (9). These differences could be due to the biological and social changes taking place during the transition from childhood to adulthood. Although significant developmental changes take place during adolescence, very few studies have examined the associations between subjective sleep and inflammation in teenagers. 

So then, which measures of sleep are actually associated with inflammation in teenagers? Do any of these associations change with age? To answer these questions, researchers at Bryn Mawr College measured both objective and subjective indices of sleep in an ethnically diverse group of teenagers aged 14-18 years old living in the Los Angeles area (10). To objectively measure sleep duration, participants wore actigraphy watches at night. These devices track the amount of movement during nighttime sleep and their use has two major advantages: 1) these devices record small sleep disturbances and movements which are often not remembered and 2) they provide accurate information about sleep/wake times. People move much less when they sleep, so actigraphy enables researchers to identify when people actually fall asleep, wake up, and get out of bed. Even if you’re just waking up and still lying in bed, the actigraphy watches can detect subtle movements that indicate a waking state. These data were examined to evaluate how long adolescents slept during the night, as well as how their sleep patterns changed throughout the week. Participants also completed the Pittsburgh Sleep Quality Inventory, a widely used questionnaire that assesses subjective sleep quality over the past month. After tracking objective and subjective indices of sleep for eight nights, researchers took blood samples by pricking the adolescents’ fingers. They assayed these samples to identify the amount of inflammatory marker CRP in the blood, which serves as an index of inflammation throughout the body. Lastly, researchers collected demographic and health data to control for variables previously known to be associated with inflammation (i.e. sex, ethnicity, socioeconomic status, and body mass index).

They found that overall, shorter sleep duration was not directly associated with higher levels of CRP. It seems like getting less sleep per night does not necessarily have any effects on inflammation during adolescence. They did, however, find that shorter sleep duration was associated with higher levels of CRP in adolescents ages 15 and under, specifically. These results suggest that the associations between objective sleep and inflammation change with age, in line with earlier findings that objective sleep is related to adolescent health and subjective sleep becomes more tied to health in adulthood (6, 8, 9). It may be that sleep duration is especially important during the rapid developmental changes occurring early in adolescence. As teenagers mature both biologically and socially, they may become less sensitive to the effects of shortened nighttime sleep and may become more sensitive to the quality of their sleep.

 In addition to measuring how long they slept, researchers also looked at sleep variability—how teenagers’ sleep duration changed throughout the week. High variability in sleep can be likened to getting normal sleep one night, staying up late to study the next night, and then sleeping extra-long the following night to compensate. Students often show greater variability if they stay up late doing their homework on weeknights and then compensate by sleeping in on the weekends. The researchers found that adolescents with greater nightly variability in sleep duration showed higher levels of CRP, regardless of age. This finding suggests that it might not be for the best to stay up late repeatedly. Such irregularity in sleep seems to have implications for systemic inflammation and the progression of CVD. Adolescents may be best served by prioritizing a consistent sleep schedule.

Lastly, subjective sleep was not associated with CRP levels. Therefore, the association with inflammation in adolescents seems to be present in objective measures rather than subjective measures of sleep. This, again, is in contrast to adults who show robust associations only in subjective measures of sleep. Thus, poor perceived sleep quality may have greater implications for physical health in adulthood.

So, what implications do these findings hold for teenagers’ daily lives? For one, a consistent bedtime may be the key to good health. After a busy week, we frequently adopt the habit of “catching up” on sleep. This irregularity in sleep duration, however, may be a key driving force for inflammation. Moreover, these findings provide insight to how the importance of sleep changes throughout the lifespan. Objective sleep may be particularly related to health for younger adolescents, whose biological systems are still developing, to get a full night’s sleep. In contrast, feeling well-rested and as though one is sleeping well may be more related to health in adults. This is why it is so important for parents to enforce a nightly bedtime for their children, even throughout the weekend. In the midst of school, extracurriculars, and hanging out with friends, teenagers should also attempt to prioritize sleep wherever possible. A consistent sleep schedule, along with a full night of restful sleep, just might be the recipe for reducing inflammation, and slowing the progression of cardiovascular disease during adolescence. 

References

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3.      Telzer, E. H., Fuligni, A. J., Lieberman, M. D., & Galván, A. (2013). The effects of poor quality sleep on brain function and risk taking in adolescence. Neuroimage, 71, 275-283. https://doi.org/10.1016/j.neuroimage.2013.01.025

4.      Lagrand, W. K., Visser, C. A., Hermens, W. T., Niessen, H. W., Verheugt, F. W., Wolbink, G. J., & Hack, C. E. (1999). C-reactive protein as a cardiovascular risk factor: more than an epiphenomenon?. Circulation, 100(1), 96-102. https://doi.org/10.1161/01.cir.100.1.96

5.      Ridker, P. M., Rifai, N., Rose, L., Buring, J. E., & Cook, N. R. (2002). Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events. New England Journal of Medicine, 347(20), 1557-1565. https://doi.org/10.1056/NEJMoa021993

6.      Hall, M. H., Lee, L., & Matthews, K. A. (2015). Sleep duration during the school week is associated with C-reactive protein risk groups in healthy adolescents. Sleep Medicine, 16(1), 73-78. https://dx.doi.org/10.1016%2Fj.sleep.2014.10.005

7.      Oda, E., Oohara, K., Abe, A., Veeraveedu, P. T., Watanabe, K., Kato, K., & Aizawa, Y. (2006). The optimal cut-off point of C-reactive protein as an optional component of metabolic syndrome in Japan. Circulation Journal, 70(4), 384-388.

8.      Larkin, E. K., Rosen, C. L., Kirchner, H. L., Storfer-Isser, A., Emancipator, J. L., Johnson, N. L., … & Redline, S. (2005). Variation of C-reactive protein levels in adolescents: association with sleep-disordered breathing and sleep duration. Circulation, 111(15), 1978-1984. https://doi.org/10.1161/01.CIR.0000161819.76138.5E

9.      Irwin, M. R. (2015). Why sleep is important for health: A psychoneuroimmunology perspective. Annual Review of Psychology, 66, 143-172.  https://dx.doi.org/10.1146%2Fannurev-psych-010213-115205

10.  Park, H., Tsai, K. M., Dahl, R. E., Irwin, M. R., McCreath, H., Seeman, T. E., & Fuligni, A. J. (2016). Sleep and inflammation during adolescence. Psychosomatic Medicine, 78(6), 677. doi: 10.1097/PSY.0000000000000340.