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
Mouse Model Links Alcohol Intake to Marijuana-like Brain Compounds
January 21, 2003
Science Daily/NIH/National Institute On Alcohol Abuse And Alcoholism
Brain molecules similar to the active compound in marijuana help to regulate alcohol consumption, according to new reports by scientists at the National Institute on Alcohol Abuse and Alcoholism (NIAAA), Bethesda, Maryland, and a separate NIAAA-supported group at several New York state research institutions.
In studies conducted with a strain of mice known to have a high preference for alcohol, the scientists found greatly reduced alcohol intake in mice specially bred to lack CB1, the brain receptor for innate marijuana-like substances known as endocannabinoids. The effect was age dependent, the Bethesda group found. The New York scientists showed that the endocannabinoid system activates a brain region known as the nucleus accumbens, which plays a major role in mediating the rewarding effects of alcohol. Both groups had shown that alcohol intake among normal mice of the same alcohol-preferring strain could be reduced by treating the animals with a drug that blocks CB1 receptors in the brain.
The new reports appear in the early online versions of the Proceedings of the National Academy of Sciences, Volume 20, Number 3, at www.pnas.org and the Journal of Neurochemistry, Volume 24, Number 4, at www.blackwell-synergy.com/servlet/useragent?func=showIssues&code=jnc in the week beginning January 20, 2003 (specific dates to be determined).
"These are important findings," notes NIAAA Director Ting-Kai Li, M.D. "Implicating yet another neurochemical mechanism in alcohol consumption opens another potential avenue for the development of new pharmacologic agents to prevent and treat alcohol problems."
The brain's multiple communication pathways employ a wide variety of signaling molecules known as neurotransmitters to relay messages from one brain cell to another. Researchers have found that alcohol affects numerous neurotransmitters and that a variety of brain pathways are involved in alcohol abuse and dependence. Determining precisely how alcohol interacts with brain cells and affects brain chemistry is an ongoing focus of research. Knowledge gained through this research helps scientists develop drugs to diminish the desire to consume alcohol and to counteract alcohol's effects.
Since their discovery in the early 1990's, endocannabinoids and endocannabinoid receptors have been studied intensely by alcohol and drug abuse researchers. Recent animal studies have suggested that the so-called "endocannabinoid system" is involved in some of the pharmacologic effects of alcohol and in drinking behavior.
In one of the current studies, researchers led by George Kunos, M.D., Ph.D., Scientific Director of NIAAA's Division of Intramural Biological and Clinical Research, found that, among the normal, alcohol-preferring mice–that is, those with intact CB1 receptors–the animals' appetite for both alcohol and food decreased with age. This occurred even though levels of endocannabinoids and the density of CB1 receptors were found to be similar in the brains of young and old mice.
"Although unexpected," says Dr. Kunos, "the observed age-dependent decline in alcohol preference in mice parallels observations in humans, in that only some teenage binge drinkers become alcoholics as adults, and that the onset of alcoholism declines with age."
The researchers found a possible explanation for this phenomenon by comparing the efficiency of the signal sent by the CB1 receptors in different regions of the brain in young and old mice. In old mice, they found diminished CB1 signaling in an area known as the limbic forebrain. The part of the limbic forebrain known as the nucleus accumbens plays a major role in mediating the rewarding properties of alcohol and cannabinoids and also is thought to help regulate appetite. The nucleus accumbens exerts its effects through the release of the neurotransmitter dopamine. Alcohol ingestion typically elicits a robust release of dopamine from the nucleus accumbens.
The second report by NIAAA-supported scientists led by Basalingappa L. Hungund, Ph.D., of the New York State Psychiatric Institute and Nathan S. Kline Institute for Psychiatric Research in Orangeburg, New York, complements the findings of the Kunos research team. Dr. Hungund and colleagues found that, in addition to showing a dramatic reduction in alcohol intake, alcohol-preferring mice that lack CB1 receptors release no dopamine from the nucleus accumbens after they drink alcohol. In mice with intact CB1 receptors, the researchers were able to abolish alcohol-induced release of dopamine from the nucleus accumbens by treating the animals with a drug that blocks CB1 receptors.
"Our results," says coauthor Balapal Basavarajappa, Ph.D., "clearly suggest that the CB1 receptor system is involved in ethanol-induced dopamine release in the nucleus accumbens and indicate that activation of the limbic dopamine system is required for the reinforcing effects of alcohol. They further suggest an interaction between the cannabinoidergic and dopaminergic systems in the reinforcing properties of drugs of abuse, including alcohol."
"Taken together," adds Dr. Kunos, "these findings provide unequivocal evidence for the role of endocannabinoids and CB1 in alcohol drinking behavior in rodents, and suggest that the CB1 receptor may be a promising pharmacotherapy target."
The National Institute on Alcohol Abuse and Alcoholism, a component of the National Institutes of Health, U.S. Department of Health and Human Services, conducts and supports approximately 90 percent of U.S. research on the causes, consequences, prevention, and treatment of alcohol abuse, alcoholism, and alcohol problems. NIAAA disseminates research findings to scientists, practitioners, policy makers, and the general public.
https://www.sciencedaily.com/releases/2003/01/030121080758.htm