Numerous different foods and beverages contain the alkaloid caffeine, including coffee, tea, cola, ice tea, chocolate and energy drinks, which makes caffeine the most commonly ingested psychoactive drug worldwide [1
]. Caffeine is a non-specific, competitive antagonist of adenosine receptors [2
]. Adenosine effects on these receptors include the up-regulation of A1 receptors and the increase of adenosine inhibition, which reduces excitatory neurotransmission, and alertness affecting sleep homeostasis [3
]. The best-established marker of the homeostatic regulation of sleep is deep sleep slow-wave activity (SWA; 1–4.5 Hz) in the electroencephalogram (EEG) [4
]. SWA is tightly coupled to prior wakefulness duration [5
] and results from highly synchronized activity of cortical neurons [6
]. Caffeine is considered to powerfully stimulate our brain networks during waking and sleep.
How caffeine affects sleep regulation has primarily been investigated in adults [7
]. These studies show that even low doses of caffeine impact the build-up of sleep pressure by reducing SWA at the beginning of the night in adult populations. These studies also show that SWA is affected by caffeine intake that directly precedes sleep [8
] or that is consumed in the morning of the same day preceding sleep [9
]. Stimulant effects of caffeine in adults also include alterations in sleep continuity (i.e.
, reduced sleep efficiency and increased sleep latency) [8
]. While these studies show that caffeine strongly affects mature sleep brain physiology, no comparable studies exist during sensitive periods of brain development [11
, in childhood or adolescence).
Caffeine consumption has significantly increased among adolescents over the past years [12
]. Similar to adults, high caffeine intake in adolescents is associated with an increase of reported sleep difficulties, sleep disturbances, and morning tiredness [13
]. One emerging question is whether high caffeine consuming children and adolescents exhibit a concomitant reduction in objective sleep quality. Furthermore, considering the growing consumption frequency of caffeine in adolescents worldwide, it is surprising that no studies have objectively quantified effects of caffeine [8
] in children and adolescents through the gold-standard measure of sleep quality, i.e.
, EEG activity. Addressing this gap in knowledge becomes particularly relevant given that a growing body of epidemiological literature reports early sleep difficulties as predictors for later psychological, emotional and social problems [15
]. The aim of the present study was to investigate the effects of high caffeine consumption on sleep physiology and associations with sleep habits in young life.
We report effects of regular caffeine consumption on sleep behavior and brain activity during sleep in children and adolescents. In particular, we examined whether caffeine consumption is associated with altered sleep habits and brain activity during children’s and adolescents’ sleep as reported in adults [8
]. First, our findings show that regular caffeine consumption in young subjects is associated with later bedtimes and shorter time in bed. Second, caffeine-consuming subjects reveal reduced SWA and alpha activity with strongest effects over prefrontal, central and occipital regions. Finally, the SWA reduction appears mostly at the beginning of the night, which is consistent with findings in adults [8
]. Our results suggest that only minor changes occur in sleep architecture (i.e.
, sleep stages) and continuity and that regular caffeine consumption in adolescents may lead to later bedtimes and reduced sleep depth, as measured by SWA.
In adults, caffeine attenuates the build-up of sleep SWA during the day [8
] and thus reduces sleepiness. We consequently expected later bedtimes in young caffeine consumers, which was confirmed with the sleep diary data. Diaries were shown to be a tool equally reliable to actigraphy for the assessment of sleep (bedtimes, sleep start [35
]). At what time of the day caffeine was consumed was variable across subjects (e.g.
, see variability of latest caffeine intake, Table 2
), which may have contributed to individual differences in the effects of caffeine. Because habitual rise times did not differ between groups, the question arises whether caffeine consumers are chronically sleep restricted, which would increase tiredness and other symptoms associated with sleep loss, such as impairment of working memory or inhibitory control [36
]. We assumed that subjective statements about morning tiredness are a reliable inverse measure for being well rested, and similarly a short reaction time in the attention task. It is interesting that these measures did not differ between groups, which may imply that daily functioning is not affected by caffeine consumption. However, as our power analysis indicates (Table 2
), larger samples may reveal additional group differences. It is conceivable that the shortened time spent in bed may increase caffeine intake throughout the subsequent day to combat daytime sleepiness [39
]. Other studies, however, have reported increased morning tiredness in high caffeine consuming adolescents, compared to controls [13
]. However, caffeine consumption in terms of exact volume has not been computed in that study and a different quantification of subjective tiredness was used, a caveat when directly comparing outcomes between studies. It will be relevant in future studies to track daytime sleepiness throughout the day and examine interactions between sleepiness and acute caffeine intake. On the other hand, if caffeine consumers were chronically sleep deprived, they might have underestimated subjective tiredness, because sleep restricted adults are largely unaware of increasing cognitive deficits [37
Alpha activity revealed topographical effects similar to SWA when contrasting caffeine consumers with the control group. A close relationship between alpha and SWA is an often-observed phenomenon (i.e.
, “alpha-delta”) that is characterized as alpha waves superimposed on slow waves [40
]. The alpha-delta relationship has been discussed in the context of the perception of sleep depth and the estimation of sleep time, however with controversy in the literature [40
]. Our finding that alpha and SWA group differences were topographically similar further supports the alpha-delta link, but it remains to be investigated whether reduced alpha power in caffeine consumers accounts for perceived sleep quality and duration in children and adolescents.
The stimulatory effect of caffeine is central. The action of the adenosine antagonist affects mainly sleep quality and the cardiovascular system [1
]. By doing so, caffeine modulates the cAMP signaling pathway [2
], which plays a key role in neural function [42
]. Adenosine accumulation, on the other hand, was suggested to prevent neurodegeneration [43
]. It is thus likely that caffeine affects neuronal plasticity. Numerous studies illustrate the importance of sleep SWA for neuronal plasticity [44
] and the caffeine induced reduction of SWA may affect synaptic plasticity during cortical maturation. Alternative pathways of action are also conceivable: Caffeine may impact plasticity via microglia, which play a key role in synaptic pruning [46
]. Chronic caffeine ingestion impacts microglia morphology and density [47
]. A further potential interference of caffeine with synaptic plasticity might originate from the blocked activation of the actin binding protein Cofilin, which is central for synaptic plasticity mechanisms [48
]. No matter what mechanisms underlie the impact of caffeine on plasticity, further research is needed to understand whether and how caffeine consumption throughout the critical period of adolescence may ultimately alter cortical maturation.
Finally, our findings are also of practical relevance in the on-going discussion about adjusting school start times to adolescent’s needs [49
]. Given that rise times are determined by school schedules, later school start times may allow caffeine consumers to be comparably well rested through compensating for later bedtimes and potentially worse sleep quality (increased subjectively reported and objectively measured wakefulness after sleep onset). Conversely, one problem of this view is the fact that caffeine consumers do not seem to compensate for reduced time in bed with increased sleep duration at weekends (no difference of time in bed between week days and weekend days). Thus, sleep need might generally be reduced in caffeine consuming children and adolescents. Additional support for this hypothesis comes from our finding that caffeine consumers exhibit reduced SWA, the best-established physiological marker of sleep need [50
]. SWA levels at the beginning of the night were lower in caffeine consumers compared to controls, but converge to equivalence in the morning hours. This convergence is in line with the subjective perception of groups being equally rested (no group difference in “tiredness”). However, considering that sleep is involved in plastic processes of neural networks [51
], it remains to be examined whether such an adaptive response to caffeine consumption that results in reduced sleep, affects development. Alternatively, we cannot exclude the possibility that children and adolescents with less deep sleep and a lifestyle involving later bedtimes have more social demands and are more prone to consume high amounts of caffeine [52
]. These data are critical for gaining insight into the possible vulnerability of the developing brain through extensive caffeine consumption. Additionally, it is possible that caffeine consumers exhibit a reduced capacity for the state of deep sleep related to cortical hyperarousal, which can be induced through caffeine [53
]. Yet, we did not find group differences in wake after sleep onset, nor did we find increased beta activity, which was proposed to reflect a cortical hyperarousal in the context of insomnia [54
]. However, these findings need to be interpreted in the context of limitations. The cross-sectional nature of the data and the rather small sample size does not allow developmental conclusions and limits the statistical power of our study. Further, the nature of the study design does not allow to address causality, and prospective examinations are required that investigate mediators that may be driving the correlation between caffeine consumption and sleep (e.g.
, social context, lifestyle, time point of caffeine intake). However, because no correlative relationship was found between bedtime and the individual extent of SWA, it is unlikely that bedtime has caused the effect of reduced SWA in a homeostatic manner.