The Long-Term Effects of Adolescent Alcohol Exposure

Alcohol is the most widely used recreational drug in the world, and under-age alcohol use is a major worldwide public health issue. National surveys show that most people in the US begin to use alcohol during adolescence, with about three-quarters of 12^th graders reporting that they have tried it and one-quarter reporting that they have consumed five or more alcoholic drinks in a row within the past two weeks.

Adolescence is broadly defined as the transition between dependence upon, and relative independence from, parents or caregivers, characterized by dramatic physical changes signalling sexual maturation of the body–and, often, by impulsivity, poor decision-making, and risky behavior, including binge drinking, defined as intermittent exposure in which 5-20 alcoholic drinks are consumed each time.

It is also an extended period of heightened neuroplasticity, during which the prefrontal cortex–involved in so-called executive functions such as planning and decision-making–undergoes extensive synaptic pruning and myelination, processes which continue well into the third decade of life. Adolescence is a highly sensitive period, during which individuals are more sensitive to the effects of alcohol and other drugs, and also susceptible to addiction and mental illness.

We still know very little about how exposure to alcohol in adolescence affects brain development, or about the long-term effects on behavior. Researchers discussed the latest findings in this field in a symposium held during the annual meeting of the Society for Neuroscience in Chicago last month.

Adolescents respond to alcohol differently from adults, said psychologist Linda Spear of Binghampton University. They are more sensitive to alcohol’s rewarding effects, and to its effects on cognitive functions such as memory, but less so to its sedative effects, which are normally what signal adults to stop drinking. As a result, they are more likely to continue drinking until they black out.

Spear described research she has done as part of the Neurobiology of Adolescent Drinking in Adulthood (NADIA) Consortium, which shows that intermittent exposure to alcohol in adolescence causes the adolescent response to it to persist into adulthood, something the researchers now refer to as Adolescent Alcohol Syndrome. Thus, adolescents who abuse alcohol may be more likely to experience alcohol-related problems as adults.

Psychiatrist Scott Swartzwelder of Duke University described his research on how alcohol affects the hippocampus, a brain structure known to be critical for memory formation. (See: One Man’s Continuing Contribution to the Science of Memory) “A blackout is a pretty serious neurological insult, but we tend to make a joke out of it socially, and there are even movies based on the premise,” said Swartzwelder.

The latest study from his group shows that intermittent alcohol exposure during adolescence causes functional and structural changes in the hippocampus that persist into adulthood. This pattern of drinking increases the proportion of immature synaptic connections relative to mature ones in the hippocampus, and this enhances signalling, because immature synapses are more active, but it could also contribute to blackouts and other alcohol-induced memory deficits, and may have other consequences: “It can diminish memory function by saturating the circuits, and it may also predispose the circuits to excito-toxicity and epileptic seizures.”

Microglia are part of the altered composition of these synaptic connections. The brain’s resident immune cells, microglia respond to injury and infection by mopping up toxins and debris, and clear away unwanted synapses in the developing and mature brain in the same way. The involvement of microglia suggests that the adolescent brain responds to alcohol exposure as if it were an injury.

Pharmacologist Fulton Crews of the University of North Carolina Medical Center and colleagues showed in 2008 that brain tissue collected from adult alcoholics at post-mortem has significantly higher levels of activated microglia compared with tissue from non-alcoholics. More recently, his team has shown that adolescent binge drinking is associated with increased expression of neuroimmune genes in the prefrontal cortex, and that this, too, persists into adulthood. This further implicates neuroimmune processes, and also suggests they may contribute to the development of alcoholism.

Adolescent alcohol abuse is associated with reductions in brain volume, too. For example, one study showed that drinking regularly before age 15 is associated with a thinner prefrontal cortex, another that the hippocampus is significantly smaller in people with alcohol use disorders compared with non-abusers, and that this volume reduction is related to the age at which alcohol consumption began.

It’s not clear if such changes are a consequence of adolescent alcohol exposure, or if they represent pre-existing differences that make some people more vulnerable to alcohol abuse.

These changes also are increasingly being linked to alterations in the extensive myelination that takes place in the adolescent prefrontal cortex, said Heather Richardson of the University of Massachusetts in Amherst.

“There’s still quite a bit of brain development going on at this time, with white matter increasing during pre-adolescence and into the twenties,” said Richardson, “and the prefrontal cortex is one of the last places to be myelinated.”

Myelination, like pruning, is critical for proper maturation of the prefrontal cortex during late adolescence, but research shows that intermittent alcohol exposure during this period can significantly interfere with the process. Heavy drinking from an early age is associated with prefrontal cortex dysfunction and cognitive impairments, as well as higher prevalence of alcohol abuse in adulthood, and all of these have in turn been linked to alterations in the white matter of the frontal lobes.

Richardson described animal experiments performed in her lab that confirm the findings of these human studies; the binge-drinking regimes they administered to adolescent rodents dramatically reduced the number and thickness of white matter tracts in the prefrontal cortex, and also impaired the animals’ performance on a working memory task.

“Our data shows that alcohol causes a decrease in prefrontal myelin and that these effects go way beyond the initial exposure,” said Richardson. “We hypothesize that adolescent binge-drinking may actually increase vulnerability to alcohol use disorder by interfering with myelination in the prefrontal cortex.”