Adolescence is a critical period for brain maturation involving a massive reorganization of cortical connectivity. An overproduction of cortical synapses during early development leads to a peak in synaptic density shortly before puberty, followed by the selective elimination of synapses during adolescence. This process is essential for optimizing the brain's connections to make it function more efficiently.

Slow wave activity (SWA) during non-rapid eye movement sleep has been proposed to reflect cortical maturation. An increase in the amplitude of the slow waves is associated with a more synchronous firing pattern among neurons. This synchronicity increases in pre-pubertal children, reaches a maximum at puberty and decreases during adolescence, mirroring the inverted U-shaped trajectory of synapse density.

Caffeine, whose consumption by adolescents has recently been increasing, is known to diminish the buildup of sleep pressure during wakefulness. Because SWA is the major electrophysiological marker of sleep pressure, Reto Huber (University Children's Hospital Zurich, Switzerland) hypothesized that caffeine might interfere with SWA, and thus the changes in synaptic density necessary for brain maturation.

Huber's team assessed sleep, behavior and electrophysiological markers of brain maturation in the juvenile rat (PLoS ONE 8, e72539; 2013). As in humans, SWA in the rat increased progressively during early development, reached a plateau during puberty and declined significantly afterward. The number of cortical synapses also declined with increased age after puberty. These changes were paralleled by behavioral changes assessed in a free exploration task: more mature animals showed increased exploration of a novel object. These findings confirmed that the rat serves as an appropriate model of the relationship between SWA during sleep and cortical maturation.

They next used this rat model to determine the effects of caffeine consumption in adolescence. After the rats reached puberty, one group was administered caffeine in their drinking water for 5 days. The caffeine-treated rats exhibited higher SWA over the next few days when compared to the non-treated rats, and the reduction in the number of synapses seen in the non-treated rats was diminished. Furthermore, the age-dependent increase in exploration seen in the non-treated rats was reduced in the caffeine-treated rats.

These findings suggest that caffeine consumption delays cortical maturation during a critical developmental period by interfering with SWA during sleep. Because the critical period of synapse elimination during adolescence is associated with psychiatric and mood disorders, increased caffeine consumption in adolescents may be linked to the higher incidences of schizophrenia and personality disorders in recent years.