The teenage brain issue

The teenage brain, as many parents may attest, is amazing yet hard to fathom. “What were they thinking?!” is a frequent complaint. Adolescents have increased risk-taking, impulsivity, emotional turmoil, and novelty-seeking behavior compared to adults. Some of the erratic behavior is blamed on “raging hormones.” What the authors of the reviews of this issue all agree is that the teenage brain is undergoing an important and dramatic transition that leaves it vulnerable to a number of environmental influences that can push it into a negative trajectory. One review alerts us to the fact that the blood-brain barrier, that protects the brain from toxins, is still maturing until the age of 20 or more. Also, take care if the largely beneficial neurohormone melatonin is being considered for therapy for adolescents, because it may interfere with the pubertal changes in the brain. The environment of the teenage/adolescent brain is challenged with increasing independence from parental and school system influences. The social influences that a teenager is more receptive to are peer pressures and the media, which are not necessarily advantageous influences. The teen years are when exposure to marijuana, alcohol, and illicit drugs first begins. Marijuana is becoming legalized state-by-state for use in the USA, whether for medicinal or recreational purposes, and most teenagers believe it to be harmless. Several authors point to significant changes in brain structure and function after exposure to these substances, including marijuana, in adolescence. The authors also provide answers to help navigate through these vulnerable years to achieve a positive trajectory, for example avoid alcohol, junk food, energy drinks, and drugs, and engage in exercise and get adequate sleep. Just what mom has always said! The authors warn us that consumption of alcohol, junk food, energy drinks, drugs, and a combination of these can interfere with the dynamic remodeling of the adolescent brain. Some of these negative effects can persist into adulthood and result in permanent neurobehavioral deficits. This vulnerability of the teenage brain is much greater than for the fully mature adult brain. On the positive side, the teenage brain is resilient and, in the right environment that includes physical exercise, a healthy diet, and adequate sleep, it can blossom and reach its full potential. Analyses of modern brain imaging shows that parameters such as a size and activity of certain brain regions correlates with behavior. These results promise a future where assays may be used to predict susceptibility to destructive behaviors, such as suicide or drug addiction, that can be forstalled or prevented if caught early on. The authors recognize that the teen years are an opportunity to positively influence brain maturation and call for an expansion of investigations into this topic. Dr. Nagel and colleagues reveal advances in the study of the brain using advanced imaging techniques that can capture the activity as well as the structure of the brain and correlate certain signature patterns with mental illness or drug addiction. The adolescent brain is known to be going through dynamic remodeling that includes sequential myelination with the frontal cortex, site of executive functions, being one of the last regions to mature. The aim is to use brain imaging data to not only diagnose, but also predict problematic conditions, such as anxiety and depression, and destructive behavior, such as suicide and drug addiction, and head off these consequences with the appropriate therapeutic approaches. These data can also be used to test the efficacy of therapies. These aims may be closer than we think, thanks to larger studies and computer learning algorithms. Brain imaging may add a significant predictive value to analysis of adolescent behavior. Dr. Quintanilla and colleagues have laid out the effects of alcohol intake from low to high doses and the aftermath which includes hangover and withdrawal…then reveals the effect on the vulnerable mitochondria so crucial to brain function. These organelles are especially needed for the nervous system, which represents a heavy consumer of energy in the body. The teenage brain is especially vulnerable not only because it is in developmental flux, but also because hangover symptoms are milder in teenagers, thus leading to rapid resumption of alcohol intake, and the prevalent culture of binge social drinking to celebrate weekends. Dr. Reichelt and colleagues tell us that junk food isn't just bad for our cardiovascular health and weight, but also for our brains. Junk food is defined as “highly palatable and rewarding, but nutritionally poor” food. Adolescents who seem to crave and exist on junk food might be at particular risk for negative effects, because of key neurotransmitter systems are “under construction” in the brain at that time. These systems are responsible for “reward signaling” and “inhibition”, and their disruption can affect eating behavior and increase impulsivity into adulthood. Drs. Curran and Marczinski warn us about the potential negative effects of energy drinks on the teenage brain. The rise in energy drink consumption often mixed with alcohol by the teen population is alarming in the light of what animal studies are showing. While research in this field is still sparse, the findings are that the contents of energy drinks, caffeine, and taurine together or alone, while potentially beneficial to brain function of adults, is likely to be detrimental to the brain function of children and adolescents, especially when mixed with alcohol. Energy drinks are often taken with alcohol, with the idea that they will counteract the effects of drinking such as sleepiness. On the contrary, consequences of imbibing the mix of energy drinks and alcohol in young rats are memory loss, an increase in anxiety, and deficits in locomoter tests. These authors point to the many gaps in this important research that urgently need to be filled, as energy drink consumption continues to rise in our society, especially in youths. Dr. Herting and colleagues support that a solution to maintaining optimal brain health is exercise, but 81% of adolescents are not getting the recommended amount, 60 min moderate to vigorous exercise per day. Regular exercise is especially beneficial to teenagers because it sets the stage for healthy adulthood habits, improves “attention, planning, problem-solving, working memory, and inhibitory control” that lead to high academic performance and are necessary for a successful career. This long list of benefits should motivate getting teens off the sofa to exercise. Drs. Onaolapo and Onaolapo explain that melatonin, an endogenous neurohormone, can be beneficial when taken as a supplement for various disorders, but cautions that its use in children and adolescents should be conducted with care because melatonin could interfere with pubertal changes. The authors reveal the amazingly broad range of effects that melatonin has in addition to its role in controlling circadian and circannual rhythms, as an anti-oxidant, as a regulator of the immune system, and as a controller of diabetes to name a few. Nonetheless, its role in regulating hormonal changes that are dramatic in adolescence leads to the caution in its use. Dr. Knudsen and colleagues explain the development of an important barrier, the blood-brain barrier (BBB), that largely protects while allowing nutrients through, can also be part of the problem by converting compounds into more toxic versions. Relevant to the teenage brain, this key barrier is comprised of endothelial cells, pericytes, astrocytes, microglia and neurons, and their products does not achieve the adult structure/function until after 20 years of age. This means that the teenage brain is more vulnerable to certain toxins than the adult brain. This review covers all the known cell and molecular mechanisms that come into play as this important barrier forms in the embryonic brain. It even touches on the evolution of the BBB that seems to emerge early on. Cephalopods (e.g., octopi) seem to have the beginnings of a BBB. The authors emphasize that the BBB at each stage of development, though “immature”, is appropriate in its function in supporting the growth of the brain; thus, hurrying along its development would not be appropriate. Dr. Nock reveals the damage that drug exposure can inflict on young adult brains, and the potential for promoting exercise to help in preventing the use of drugs and treating drug addiction. This includes the use of marijuana that is widely thought to be harmless, and its use is becoming legalized state-by-state and soon to be legalized in the next country over, Canada. As with alcohol, opioids and other drugs, including marijuana, have a big negative impact on the structure and function of the adolescent brain that could be permanent. “Assisted exercise” is the mechanically assisted exercise that allows the individual to pedal 35% faster than their voluntary rate. This form of exercise seems to be even more effective than standard exercise regimens in steering young adults from substance use and abuse. Michiko Watanabe Department of Pediatrics, Case Western Reserve University, School of Medicine, Cleveland, Ohio Correspondence Michiko Watanabe, Department of Pediatrics, Case Western Reserve University, School of Medicine, Cleveland, Ohio. Email: Mxw13@case.edu

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