Genetics of Adolescent Alcohol Use and Disorders : Part 3

by National Institute of Health

(Page 4 of 5)

Distribution Volume

One feature of puberty is the appearance of gender differentiation in body fat. Girls have increased fat as a percentage of body weight. Because ethanol is soluble in water, the distribution volume for ethanol is decreased in girls. Thus, girls experience higher blood alcohol concentrations when they receive an ethanol dose that is proportionate to BWt. In contrast, boys typically gain muscle mass and lose fat, increasing VD and thus reducing the BAC reached after they receive an ethanol dose proportionate to body weight.

Elimination of Alcohol

Women reportedly metabolize alcohol faster than do men, a difference that probably becomes evident over the period of pubertal development. Similarly, the reported variation in alcohol elimination associated with the menstrual period among women presumably develops over the same age range. Whether the gender difference is an effect of changes in males or females (or both) should be determinable in animals.

Absorption Rate and Bioavailability

Both the rate of alcohol absorption and bioavailability are largely influenced by prandial state (the quantity - and perhaps quality - of food recently ingested). Gender differences in this interaction, particularly as they may affect first-pass metabolism (the metabolism of alcohol in the stomach and its first passage through the liver), have been suggested by some but not all studies in adults. Nothing is known about pre- vs. post-pubertal changes.

Neurobiological Mechanisms of Adolescent
Alcohol Abuse and Dependence

Over the past 10 years, basic human and animal research has generated important new knowledge in the following areas: 1. identification of neurobiological and behavioral risk factors for alcohol abuse and dependence; 2. determination of the consequences of acute and chronic heavy drinking during adolescence on brain and behavioral maturation; 3. understanding of the neuropharmacological, neuroanatomical, hormonal, and behavioral mechanisms underlying the variable response to alcohol across developmental stages; and 4. assessment of the contribution of early alcohol exposure (during juvenile and adolescent periods) to excessive drinking and abnormal cognitive and social functioning in adulthood. Below is a summary of the current research findings on the neurobiological mechanisms involved in adolescent drinking.

Predisposition to Alcoholism

Neurobehavioral research in human adolescents has largely been limited to studies of neural risk markers in children with a positive family history of alcoholism. These investigations suggest that there are subtle heritable neurocognitive and neurophysiological abnormalities in children of recovering alcoholics which could be early indicators of risk for alcoholism. The most common finding is reduced P3 amplitude of the event-related potential in children with familial alcoholism. More recently, other neural risk factors that predate the onset of heavy drinking are being considered in at-risk youth, such as sleep electroencephalographic abnormalities and changes in brain structure and function. For example, it was found that youths with dense family histories of alcoholism show reduced right amygdala volumes, which correlate with P3 amplitudes. More importantly, the neurophysiological and neuroanatomical abnormalities may be most pronounced during the prepubertal and adolescent years. This latter finding underscores the importance of considering developmental phases when attempting to identify early risk markers for alcoholism.

Taken together, these studies indicate that subtle neural abnormalities may underlie the heritable aspects of alcohol use disorders. However, some studies suggest that family history of AUDs primarily affects brain functioning in people who also show conduct disorder, antisocial personality disorder, sensation seeking, behavioral undercontrol, difficult temperament, or poor impulse control. Understanding these brain characteristics helps us to appreciate the brain abnormalities that may be produced by personal alcohol involvement as opposed to features that are attributable to predrinking risk factors.

As discussed in the genetics section, animal models have been used to study heritable factors that contribute to alcoholism. The selectively bred alcohol-preferring and high alcohol drinking lines of rats are particularly good models for studying the neural mechanisms of early onset drinking because they readily consume alcohol in the postnatal weaning stage and attain adult levels of intake by adolescence. Even as early as adolescence, innate differences are observed in the P and HAD lines in several neurobiological markers that have been associated with a genetic susceptibility to high alcohol drinking.

Further, nonhuman primates with low levels of the serotonin metabolite 5-HIAA have been used to model key aspects of adolescent behavior, such as impulsiveness and aggressiveness, tolerance to alcohol's effects on initial exposure to alcohol, and the ability to drink excessive amounts of alcohol. Increased availability of serotonin transporters and low platelet monoamine oxidase activity also are thought to be traitlike markers in nonhuman primates associated with alcohol sensitivity and increased alcohol consumption.

This pattern of behavioral and biochemical markers is similar to that predisposing to early onset alcoholism in humans and is influenced by genotype-environment interactions. For example, recent studies in rhesus monkeys found that serotonin transporter genotype influences cerebrospinal fluid 5-HIAA levels as well as alcohol sensitivity, preference, and consumption, but only in animals exposed to early life stress. Thus, it is important to understand the relationships among environmental factors, genetic backgrounds, and neurobiological markers in predisposing an individual to alcoholism.

About the Author

NIH is the nation's medical research agency - making important medical discoveries that improve health and save lives. The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the primary Federal agency for conducting and supporting medical research.