Binge drinking in adolescence may increase risk for anxiety later in life

March 11, 2019

Science Daily/University of Illinois at Chicago

Researchers have found that adolescent binge drinking, even if discontinued, increases the risk for anxiety later in life due to abnormal epigenetic programming.

A growing body of evidence supports the idea that alcohol exposure early in life has lasting effects on the brain and increases the risk of psychological problems in adulthood. Now, researchers at the University of Illinois at Chicago have found that adolescent binge drinking, even if discontinued, increases the risk for anxiety later in life due to abnormal epigenetic programming. The findings of the study, which was conducted in animals, was published in the journal Biological Psychiatry.

"Binge drinking early in life modifies the brain and changes connectivity in the brain, especially in the amygdala, which is involved in emotional regulation and anxiety, in ways we don't totally understand yet," said Subhash Pandey, professor of psychiatry in the UIC College of Medicine, director of the UIC Center for Alcohol Research in Epigenetics and lead author of the study. "But what we do know is that epigenetic changes are lasting, and increase susceptibility to psychological issues later in life, even if drinking that took place early in life is stopped."

"Epigenetics" refers to chemical changes to DNA, RNA, or specific proteins associated with chromosomes that change the activity of genes without changing the genes themselves. Epigenetic alterations are required for the normal development of the brain, but they can be modified in response to environmental or even social factors, such as alcohol and stress. These kinds of epigenetic alterations have been linked to changes in behavior and disease.

Adolescent rats were exposed to ethanol (a type of alcohol) for two days on and two days off or to the same protocol using saline for 14 days. All rats underwent an assessment for anxiety.

Pandey and his colleagues exposed adolescent rats to a regimen designed to mimic binge drinking. Those rats exhibited anxious behavior later in life, even if the binge drinking regimen stopped in late adolescence and the rats were allowed to mature to adulthood without any further exposure to alcohol.

These rats also had lower levels of a protein called Arc in the amygdala. Arc is important for the normal development of synaptic connections in the brain. Rats with less Arc also had about 40 percent fewer neuronal connections in the amygdala compared with rats that weren't exposed to alcohol.

"We believe that the decrease in Arc levels is caused by epigenetic changes that alter the expression of Arc, and an enhancer RNA, which modifies the expression of Arc. These changes are caused by adolescent alcohol exposure," said Pandey.

"Exposure to alcohol causes epigenetic reprogramming to occur, leading to molecular changes in the amygdala, which are long-lasting, even in the absence of more alcohol," said Pandey, who is also a senior research career scientist at the Jesse Brown VA Medical Center. "If the amygdala has deficits in its wiring or connectivity, and these modifications are long-lasting, the individual is at risk for psychological issues based on difficulties in regulating emotions, such as anxiety or depression and the development of alcohol use disorder later in life."

https://www.sciencedaily.com/releases/2019/03/190311125156.htm

Youth who have their first drink during puberty have higher levels of later drinking

May 18, 2013

Science Daily/Alcoholism: Clinical & Experimental Research

Research shows that the earlier the age at which youth take their first alcoholic drink, the greater the risk of developing alcohol problems. Thus, age at first drink (AFD) is generally considered a powerful predictor of progression to alcohol-related harm. A new study shows that individuals who have their first drink during puberty subsequently have higher drinking levels than do individuals with a post-pubertal drinking onset.

Results will be published in the October 2013 issue of Alcoholism: Clinical & Experimental Research and are currently available at Early View.

"Most teenagers have their first alcoholic drink during puberty, however, most research on the risks of early-onset alcohol use up to now has not focused on the pubertal stage during which the first alcoholic drink is consumed," said Miriam Schneider, leader of the Research Group Developmental Neuropsychopharmacology at the Central Institute of Mental Health, University of Heidelberg, as well as corresponding author for the study. "Common thinking in alcohol research was that the earlier adolescents begin, the more deleterious become their drinking habits. However, a closer look at the statistics revealed a peak risk of alcohol use disorders for those beginning at 12 to 14 years of age, while even earlier beginners seemed to have a slightly lower risk. Since timing of puberty is not a simple function of chronological age, and also greatly differs between the sexes, the pubertal phase at first drink may therefore represent a stronger and better indicator for subsequent alcohol-related problems than simply the age."

"Usually this type of research has to be done retrospectively, and those studies are not very reliable," added Rainer Spanagel, head of the Institute of Psychopharmacology at the University of Heidelberg. "Prospective longitudinal studies like the one here … are able to provide reliable conclusions on such a clinically and highly relevant research question. Alternatively, animal studies can be very informative -- and which the researchers have also provided."

"Adolescents have their first drink at very different ages," explained Schneider. "It would be unethical to make adolescents have their first drink in the course of a study, so this variable requires a longitudinal epidemiological study or experimental animal research to assess drinking behavior. Also, the determination of the pubertal stage at AFD is not trivial; even our study had to rely on estimations. Third, it takes longitudinal studies to assess drinking data in early adulthood. Fourth, both drinking behavior and pubertal development can be traced back to common factors such as psychosocial adversity. Finally, while puberty and adolescence are overlapping time periods, with puberty being a part of adolescence, the terms cannot be used interchangeably. 'Puberty' refers to the time period during which sexual maturity is achieved. 'Adolescence' refers to the gradual period of behavioral and cognitive transition from childhood to adulthood, where adult behavioral abilities are acquired, and the boundaries of this period are not precisely defined. Girls complete puberty much earlier than boys, indicating a difference in timing of neurodevelopmental processes."

Schneider and her colleagues determined pubertal age at first drink in 283 young adults (152 females, 131 males) that were part of a larger epidemiological study. In addition, the participants' drinking behavior -- number of drinking days, amount of alcohol consumed, and hazardous drinking -- was assessed at ages 19, 22, and 23 years via interviews and questionnaires. Furthermore, a rodent study concurrently examined the effects of mid-puberty or adult alcohol exposure on voluntary alcohol consumption in later life by 20 male Wistar rats.

"Both studies revealed that those individuals that initiated alcohol consumption during puberty tended to drink more and also more frequently than those starting after puberty," said Schneider.

"In other words," said Spanagel, "this study indicates that the period of puberty might serve as a risk window for AFD. Results also show a higher Alcohol Use Disorders Identification Test (AUDIT) score later in life in those individuals who had their AFD in puberty. A higher AUDIT score is indicative of a high likelihood of hazardous or harmful alcohol consumption. This information is of great relevance for intervention programs. Even more interesting, neither pre-pubertal nor post-pubertal periods seem to serve as risk-time windows. Therefore, intervention programs should be directed selectively towards young people in puberty."

Both Schneider and Spanagel noted the influence of a high degree of brain development that occurs during puberty.

"Numerous neurodevelopmental alterations are taking place during puberty, such as maturational processes in cortical and limbic regions, which are characterized by both progressive and regressive changes such as myelination and synaptic pruning," said Schneider. "Typically, an overproduction of axons and synapses can be found during early puberty, followed by rapid pruning during later puberty, indicating that connections and communication between subcortical and cortical regions are in a highly transitional state during this period."

"Puberty is a phase in which the brain reward system undergoes major functional changes," said Spanagel. "For example, the endocannabinoid and dopamine systems are at their peak and these major neurobiological changes are reflected on the behavioral level; reward sensitivity is highest during puberty. Therefore, during puberty the brain is in a highly vulnerable state for any kind of reward, and drug rewards in particular. This high vulnerability might also affect reward seeking, or in this particular case, alcohol seeking and drinking behavior later in life."

"In summary," said Schneider, "puberty is a very critical developmental period due to ongoing neurodevelopmental processes in the brain. It is exactly during puberty that substances like drugs of abuse -- alcohol, cannabis, etc. -- may induce the most destructive and also persistent effects on the still developing brain, which may in some cases even result in neuropsychiatric disorders, such as schizophrenia or addictive disorders. Prevention work therefore needs to increase awareness of specific risks and vulnerability related to puberty."

https://www.sciencedaily.com/releases/2013/05/130518153740.htm

Vaping popular among teens; opioid misuse at historic lows

NIH's 2017 Monitoring the Future survey shows both vaping and marijuana are more popular than traditional cigarettes or pain reliever misuse

December 14, 2017

Science Daily/NIH/National Institute on Drug Abuse

Nearly one in three 12th graders report past year use of some kind of vaping device, raising concerns about the impact on their health. What they say is in the device, however, ranges from nicotine, to marijuana, to "just flavoring." The survey also suggests that use of hookahs and regular cigarettes is declining.

These findings come from the 2017 Monitoring the Future (MTF) survey of eighth, 10th and 12th graders in schools nationwide, reported today by the director of the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health, along with scientists from the University of Michigan, who conduct the annual research. The survey asks teens about "any vaping" to measure their use of electronic vaporizers. It is important to note that some research suggests that many teens don't actually know what is in the device they are using, and even if they read the label, not all labeling is consistent or accurate.

The survey shows that 27.8 percent of high school seniors reported "vaping" in the year prior to the survey, which was taken in the beginning of 2017. When asked what they thought was in the mist they inhaled the last time they used the vaping device, 51.8 percent of 12th graders said, "just flavoring," 32.8 percent said "nicotine," and 11.1 percent said "marijuana" or "hash oil." The survey also asks about vaping with specific substances during the past month, with more than one in ten 12th graders saying they use nicotine, and about one in twenty reporting using marijuana in the device.

"We are especially concerned because the survey shows that some of the teens using these devices are first-time nicotine users," said Nora D. Volkow, M.D., director of NIDA. "Recent research suggests that some of them could move on to regular cigarette smoking, so it is critical that we intervene with evidence-based efforts to prevent youth from using these products."

The survey also indicates that while opioid overdose rates remain high among adults, teens are misusing opioid pain medications less frequently than a decade ago, and are at historic lows with some of the commonly used pain medications. For example, past year misuse of the opioid pain reliever Vicodin among high school seniors dropped to its lowest point since the survey began measuring it in 2002, and it is now at just 2 percent. This compares to last year's 2.9 percent, and reflects a long-term decline from a peak of 10.5 percent in 2003.

In overall pain medication misuse, described as "narcotics other than heroin" in the survey, past year misuse has dropped significantly among 12th graders since its survey peak in 2004 -- to 4.2 percent from 9.5 percent. Interestingly, teens also think these drugs are not as easy to get as they used to be. Only 35.8 percent of 12th graders said they were easily available in the 2017 survey, compared to more than 54 percent in 2010.

"The decline in both the misuse and perceived availability of opioid medications may reflect recent public health initiatives to discourage opioid misuse to address this crisis," added Volkow. "However, with each new class of teens entering the challenging years of middle and high school, we must remain vigilant in our prevention efforts targeting young people, the adults who nurture and influence them, and the health care providers who treat them."

The 2017 survey also confirms the recent trend that daily marijuana use has become as, or more, popular than daily cigarette smoking among teens, representing a dramatic flip in use between these two drugs since the survey began in 1975. In the past decade, daily marijuana use among 12th graders has remained relatively consistent, but daily cigarette smoking has dropped.

When combining responses in all three grades, data suggest past year marijuana use is up slightly to 23.9 percent, from 22.6 percent last year, but similar to 2015 rates (23.7 percent). However, because overall marijuana rates remain stable, researchers continue to carefully monitor any potential trends as they emerge. The survey indicates that significantly fewer teens now disapprove of regular marijuana use, with 64.7 percent of 12th graders voicing disapproval, compared to 68.5 percent last year. The survey reports that high school seniors in states with medical marijuana laws are more likely to have vaped marijuana and consumed marijuana edibles than their counterparts without such laws. For example, survey data suggests that 16.7 percent of 12th graders in states with medical marijuana laws report consuming edibles, compared to 8.3 percent in states without such laws.

Inhalant use -- the one category of drug use that is typically higher among younger students -- is back up to 2015 levels among eighth graders, measured at 4.7 percent, compared to 3.8 percent in 2016. However, rates are still low, showing a significant decline from peak rates in 1995, when 12.8 percent of eighth graders reported using an inhalant to get high in the past year.

Overall, illicit drug use other than marijuana and inhalants, remains the lowest in the history of the survey in all three grades, with 13.3 percent of 12th graders reporting past year use, compared to 9.4 percent of 10th graders and 5.8 percent of eighth graders. These successes underscore the importance of continuing evidence-based prevention programs targeting children approaching their teenage years.

After years of steady decline, binge drinking appears to have leveled off this year, and public health researchers will be closely watching these behaviors in the coming years. However, rates are still down significantly from the survey's peak years. Binge drinking is defined as having five or more drinks in a row sometime in the last two weeks.

"While binge drinking among eighth, 10th, and 12th grade students remains well below the levels seen a decade ago, the downward trend in binge drinking appears to have slowed somewhat in recent years," said George F. Koob, Ph.D., director of the National Institute on Alcohol Abuse and Alcoholism. "This may signal a need for more emphasis on alcohol prevention strategies in this age group."

Monitoring the Future has been conducted by researchers at the Institute for Social Research at the University of Michigan at Ann Arbor since 1975, expanding the study periodically to include additional grades and topic areas. It is the only large-scale federal government survey that releases findings the same year the data is collected.

Other highlights from the 2017 survey:

Illegal and Illicit Drugs:

·     Reported heroin and methamphetamine use remain very low among the nation's teens at less than 0.5 percent in past year measures.

·     Cocaine use remains low in teen students. For example, 12th graders report past year use at 2.7 percent, after a peak of 6.2 percent in 1999.

·     Past year use of anabolic steroids, which peaked at 2.5 percent among the nation's 12th graders in 2004, is now at 1.1 percent.

·     Past year use of LSD among 12th graders is at 3.3 percent, reflecting a modest but significant increase in the past five years. Use still remains lower compared to its peak in 1996 of 8.8 percent.

·     Past year use of K2/Spice, referred to as "synthetic marijuana" in the survey, was reported at 3.7 percent among 12th graders, down from 11.3 percent five years ago. There was a significant drop in past year use among eighth graders, from 2.7 percent in 2016 to 2 percent this year.

Other Prescription Drugs:

Reflecting an historic low, high school seniors reported past year misuse of the prescription opioid Oxycontin at 2.7 percent, compared to 5.5 percent at its peak in 2005.

Misuse of prescription stimulants, commonly prescribed for ADHD symptoms, is mostly stable compared to last year, with 5.5 percent of 12th graders reporting past year misuse of Adderall. In fact, this represents a significant drop for this age group from five years ago when misuse peaked at 7.6 percent.

Past year misuse of the therapeutic stimulant Ritalin among 12th graders is at 1.3 percent, nearly a record low since 2001 when it was first measured at 5.1 percent. There was a significant decline this year among eighth graders' past year misuse, reported at 0.4 percent in 2017, down from 0.8 percent last year, and significantly down from 2.9 in 2001. Other Tobacco Products:

Hookah smoking has dropped for the second year in a row with 10.1 percent of seniors reporting past year use compared to 13 percent last year, down from 22.9 percent in 2014. The survey began measuring hookah smoking in 2010.

As for little cigars, 13.3 percent of high school seniors say they smoked little cigars in the past year, from a peak of 23.1 percent in 2010, when it was first included in the survey.

Attitudes and Availability:

The survey also measures attitudes about drug use, including perceived availability and harmfulness, as well as disapproval of specific drugs. Generally, attitudes grow more favorable towards drug use as teens get older.

·     In 2017, 79.8 percent of eighth graders said they disapprove of regularly vaping nicotine, but that number drops to 71.8 percent among 12th graders.

·     Only 14.1 percent of 12th graders see "great risk" in smoking marijuana occasionally, down from 17.1 percent last year and a staggering drop from 40.6 percent in 1991, but similar to rates when the survey was started in 1975 (18.1 percent).

·     There was a significant change in how eighth graders view K2/Spice (which the survey calls "synthetic marijuana"). In 2017, 23 percent said trying it once or twice would put users at great risk, compared to 27.5 percent in 2016.

·     The survey indicated that 23.3 percent of 10th graders say it is easy to get tranquilizers, up from 20.5 percent last year.

Overall, 43,703 students from 360 public and private schools participated in this year's MTF survey. Since 1975, the survey has measured how teens report their drug, alcohol, and cigarette use and related attitudes in 12th graders nationwide. Eighth and 10th graders were added to the survey in 1991. Survey participants generally report their drug use behaviors across three time periods: lifetime, past year, and past month. Questions are also asked about daily cigarette and marijuana use. NIDA has provided funding for the survey since its inception to a team of investigators at the University of Michigan at Ann Arbor, currently led by Dr. Richard Miech. MTF is funded under grant number DA001411.

https://www.sciencedaily.com/releases/2017/12/171214092235.htm