Nov. 8, 2007 — Teenagers and adults often don’t see eye to eye, and new brain research is now shedding light on some of the reasons why. Although adolescence is often characterized by increased independence and a desire for knowledge and exploration, it also is a time when brain changes can result in high-risk behaviors, addiction vulnerability, and mental illness, as different parts of the brain mature at different rates.
Recent imaging studies in humans show that brain development and connectivity are not complete until the late teens or early twenties. Combining these observations with those of experimental research, it is becoming clear that the status of both inhibitory and excitatory brain chemical systems, and connectivity between brain regions, is unique in teenagers. The teenage brain is significantly different from both the young child and the fully mature adult. In other words, the teenage brain is not just an adult brain with fewer miles on it!
The teenage brain may be more responsive to environmental stimuli and, although this may facilitate learning rates, it may also make this group more susceptible to negative stimuli, such as stress and substances of abuse and addiction. The research presented here highlights some important new advances in understanding the unique status of the teen brain.
In new research, animals exposed to either restraint stress or social isolation during puberty did not grow as fast as their unstressed counterparts and gained the least weight during adolescence, suggesting that these two kinds of stressors add up to worsen the overall effects of stress, says Russell Romeo, PhD, of Rockefeller University in New York, now at Barnard College, also in New York.
Using a behavioral test that measures how long it takes animals to give up in an aversive situation, Romeo found that animals that experienced stress during adolescence struggled less and gave up faster, suggesting that they were experiencing greater depressive-like learned helplessness behavior. Similar to the growth rates, animals experiencing both stressors exhibited the greatest level of depressive-like behavior.
Finally, measurements of corticosterone, a stress hormone, in the blood showed that animals exposed to stress during puberty had higher levels in adulthood. “We believe that stress during puberty, and not just long periods of stress, is what leads to these changes in depressive behaviors and physiological measures, as animals that were exposed to the same amount of stress, but after puberty, showed none of these changes,” Romeo says.
Many studies of adolescent boys and girls show that exposure to stress during puberty may contribute to an individual’s vulnerability to depression. In an effort to model how adolescent stress exposure affects neurobehavioral function in animals, Romeo and his colleagues investigated whether physical or psychological stressors experienced during puberty-for example, one hour of restraint stress every other day or social isolation-influence growth, depressive-like behaviors, and levels of stress hormones in adulthood.
Humans suffering from typical depression have three main symptoms: weight loss, feelings of learned helplessness, and elevated levels of stress hormones. Romeo’s studies in rats provide evidence that these symptoms of depression can be replicated in an animal model. They also provide a way to study stress-induced behavioral changes during adolescence and may help in the development of treatments or interventions to either prevent or reverse these behavioral and physiological problems.
Scientists also are researching how the developing brain responds differently to drugs of abuse such as stimulants and examining the periods during which adolescents are most vulnerable to addiction. Research shows that the teenage brain may be particularly vulnerable to the negative effects of drugs, including increased susceptibility to addiction later in life and emotional and behavioral difficulties, which could persist and become a lifelong disability.
A new study reveals that, with repeated binges, the drug ecstasy’s effect on social behavior grows more pronounced and lasts well beyond the active effects of the drug, says Jean Di Pirro, PhD, of Buffalo State College in New York. Moreover, repeated ecstasy binges cause long-term changes in body temperature regulation and levels of the brain chemicals serotonin and oxytocin. These results also suggest that binge use of ecstasy may not produce the increase in social behavior typically described by users. Reduced social contact and altered sensory experiences, such as reduced pain sensitivity, during adolescence may have serious implications for the development of normal adult social behavior and mental health.
“Animal models show unequivocally that ecstasy produces changes in the brain, like neurotoxicity of serotonin neurons, and behavior such as increased social avoidance that far outlast the immediate effects of the drug,” Di Pirro says.
In other research, scientists have found that adolescents maintain drug-related associations longer than adults, leading to a greater likelihood of relapse. Once adolescent animals learn to prefer environments previously paired with cocaine, they require 75 percent more time to lose these preferences compared with adults. These data suggest that during adolescence, drug exposure will lead to addiction that will be more difficult to treat by abstinence, says Heather Brenhouse, PhD, and her colleague S. L. Anderson, PhD, of Harvard Medical School and McLean Hospital in Belmont, Mass.
Adolescents also will resume drug-seeking behavior more strongly than adults when exposed to a small reminder dose of cocaine. Based on the adolescent’s greater propensity to form strong associations with rewarding stimuli, Brenhouse says, “extended treatment that involves substitution for different rewards, such as exercise or music, may be a more appropriate approach than adult-based rehabilitation of abstinence.”
“To our knowledge, this information provides the first preclinical evidence that during adolescence, drug exposure produces stronger memories for drug-paired cues and contexts than in adults. Furthermore, adolescents are more susceptible to relapse after less initial drug exposure,” says Brenhouse.
In the same manner that Pavlov’s famous dogs salivated in response to the sound of a bell, an addict will perform drug-seeking behaviors when he or she encounters cues previously paired with drug use. Normally, the ability to associate cues in the environment with pleasurable feelings ensures the survival of an infant, through childhood and beyond. During adolescence, however, the need arises to make one’s own decisions about what associations are important and worth remembering. Drugs of abuse pose an unnaturally high degree of stimulation to the reward system and may lock in a memory for its associated cues at the expense of other information.
“Adolescents therefore appear to hold stronger memories for these rewarding events, which may make extinction treatment more difficult and relapse more probable,” Brenhouse says.
“By understanding these processes during adolescence, we can identify unique targets for treatment and prevention of drug abuse and addiction during this critical stage of development,” says Brenhouse. “We believe that adolescents are more predisposed to process and store reward-related information differently, and therefore will require different addiction treatment strategies than adults.”
In other research, a new study shows an increase in the prevalence of frequent cannabis use among youngsters accompanied by a decrease in age of first use. Use starts at a younger age and more potent forms of the drug are now available, says Gerry Jager, PhD, of the Rudolf Magnus Institute of Neuroscience at the University Medical Center Utrecht, in the Netherlands.
Jager and her colleagues studied the consequences of frequent cannabis use during adolescence for memory, learning, and brain development, using functional magnetic resonance imaging (fMRI).
Several studies indicate that the severity of cannabis use on mental health and cognition is highly dependent on the age when cannabis use begins. The reason for this could be that 1) those who begin cannabis use early in adolescence are more likely to become heavily dependent; or that 2) the brain is still maturing and is vulnerable to persistent alterations in brain function. Thus, the effects of frequent cannabis use during adolescence could be more serious than during adulthood.
In an fMRI study, Jager’s lab examined 10 boys, aged 15 to 18 years, who were regular cannabis users, with use varying from once a week up to daily, for about two years. They were compared with nine non-using peers, matched for age, IQ scores, and alcohol use. All participants had to abstain from cannabis and alcohol for at least one week prior to testing to avoid any lingering effects of the drug. This was checked by testing urine samples for the presence of drug metabolites.
Subjects performed a memory task in an fMRI scanner, which showed that all subjects activated brain areas, including parts of the frontal and temporal lobes, that are well-known for their involvement in memory and in learning, says Jager.
The cannabis users activated the same brain regions as their non-using peers and performed the task equally well. However, the adolescent cannabis users displayed higher levels of activity than the controls. With task performance being normal, this could indicate that the brain has to work harder to maintain normal performance. It is unlikely that this effect is due to any lingering pharmacological effect of cannabis, as all of the adolescents were abstinent from cannabis for at least one week prior to scanning. Nevertheless, it remains to be seen whether the increased brain activity persists after more prolonged periods of abstinence.
Other research shows that the brain systems involved in reward processing are not yet fully developed in children and adolescents and that adolescents tend to behave in a more risky and impulsive manner than adults and children, says Jessica Cohen, MA, at the University of California, Los Angeles.
Moreover, adolescents tend to be more sensitive to the differences between various amounts of reward than children are, reinforcing the finding that neural areas sensitive to rewards are more fully developed in adolescents than in children. “This may help explain why adolescents tend to engage in risky activities that may result in immediate rewards more often than children,” Cohen says.
The findings come from an fMRI study involving 26 participants ranging in age from 10 to 19 years old. The group of children ranged from 10 to 12 years old, and the group of adolescents ranged from 14 to 19 years old. All participants played a computer game while pictures were taken of their brains in an fMRI machine.
All participants displayed activity in areas in the brain called the amygdala, ventral striatum, and medial prefrontal cortex on trials when they received rewards, as compared with those when they did not. Each of those areas has been associated in previous studies with increased activity when people are rewarded. Behaviorally, adolescents were more sensitive to different reward values than children were, as demonstrated by changes in the speed of responding to stimuli associated with different rewards in adolescents but not in children. Correlations with age were conducted with the neural data to determine if there were areas of the brain that portrayed the noted increased behavioral sensitivity to reward in adolescents.
An interesting relationship was observed in the striatum, an area associated with learning and receipt of reward. Some subregions within the striatum showed age-related changes in response to greater rewards and others to smaller rewards. “These results imply that the striatum may aid reward-related learning by increasing the sensitivity to both positive and negative differences in reward value, not only by increasing sensitivity to more rewarding stimuli,” says Cohen.
“Armed with the knowledge that adolescents are more sensitive to reward than younger children, yet realizing, based on previous studies, that their neural regions involved in self-control are not fully developed,” says Cohen, “may help clinicians understand why adolescents engage in potentially detrimental yet appealing risky behavior, such as substance abuse, and how better to teach and encourage more adaptive behavior.”
In summary, research is just beginning to shed light on how previous assumptions about the teen may be incorrect. At this time, the teenage demographic is the largest worldwide, and this population has unique educational, social, and emotional needs. Consideration of the effects of substance abuse and stress needs to take into account the possible greater consequences in the teen compared to the adult.
Much research on early brain development has translated to the field of early education, and that on the aging brain is having a major impact on developing therapeutic strategies for disorders such as dementia. However, the unique features of the teenage brain are only recently being recognized and will likely have major implications for educational and medical approaches to those in this age group.