Risk Factors
Certain characteristics or factors make persons more likely to develop alcoholism; they include family history of the disorder, negative environment, emotional stress, access to alcohol, young age at first use, being in the age range of eighteen to twenty-nine, male gender, and low level of education. Persons of certain races or ethnic origins, the unmarried, and children of alcoholics are more likely to become dependent on alcohol. Mental disorders such as major depression, anxiety, bipolar disorder, and antisocial personality disorder (ASPD) are associated with the development of alcoholism and may also be hereditary. Antisocial personality disorder has been referred to as the most important risk factor for alcoholism.
Etiology and Genetics
Alcoholism is a relatively common chronic and relapsing disorder that results in significant health and social consequences. Alcohol has a relatively high addictive potential in the general population and is even higher in susceptible individuals. Several epidemiology studies have been conducted to attempt to categorize genes and characteristics related to alcohol dependence. However, much is still not known about this disease and the role of genetics in the development, course, and outcome of alcoholism.
Genes under investigation for their potential role in this disorder are typically grouped by involvement in the metabolism of alcohol, rewarding circuits, and response to alcohol dependence treatment. The enzymes responsible for hepatic alcohol metabolism are alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH); the corresponding candidate genes are ADH2*2, ADH3*1, and ALDH2*2. Protective genes (associated with reduced alcohol consumption) are ADHB*2 and are found in Asians and Israeli Jews, while ADH1C*2 appears to protect against complications related to alcoholism, such as cirrhosis and pancreatitis. Gamma-aminobutyric acid (GABA) receptors are the most important inhibitory receptors and are involved in the rewarding circuit; alcohol acts as an agonist or activator of the GABAA receptor. Scots, Germans, Native Americans, and Finns have variants of GABRA6 and GAD that are associated with alcoholism.
Alcohol increases the concentration of dopamine in the brain and is important in reinforcing its effects. A variant in the DRD2 gene of the dopamine D2 receptor may be a vulnerability gene for alcohol dependence; however, data are conflicting. Presence of the DAT1 gene (which codes for the dopamine transporter and is responsible for dopamine reuptake) is associated with worse outcomes during alcohol withdrawal, such as seizures. Many other genes are linked to physiologic markers and to the diagnosis of alcohol dependence, including HTT, CRF, CRF1, CYP2EI, GABRA1, COMT, and DRD1. Psychiatric illness and high-risk behaviors may also be genetically linked and direct persons to select environments associated with dependence.
The genes involved in the immune system and the biological clocks are also investigation for their roles in alcoholism. Research conducted in 2011 and 2012, for example, showed that inflammatory responses in the brain, which inhibit judgment, and disruptions to the circadian rhythm may increase the risk for alcohol dependence.
Another line of inquiry is the interaction between alcohol consumption and epigenetics, the way in which genes are expressed or suppressed. According to the National Institute on Alcohol Abuse and Alcoholism's 2013 report on epigenetics, researchers have found that alcohol use may impair or disrupt gene expression in the liver, gastrointestinal tract, and brain. Studies also suggest that it may play a part in the development of cancers of the liver, breast, respiratory tract, and digestive tract as well as in fetal alcohol syndrome.
Symptoms
Early behavioral symptoms of alcoholism include frequent intoxication, a pattern of heavy drinking, drinking alone or in secret, or drinking alcohol in high-risk situations (such as drinking and driving). Erratic or dramatic changes in behavior with alcohol consumption, “blacking out,” or not remembering events that occurred while drinking, may also be signs of the disorder. Symptoms of alcohol dependence may become worse over time. The physical symptoms of alcoholism are many and can include jaundice (yellowing of skin or eyes), hepatitis (enlarged liver), abdominal pain, nausea and vomiting, infections, malaise (not feeling well), weight loss, fluid retention, problems with memory, and anorexia (decreased eating). Laboratory analyses may reveal increased liver enzymes, low potassium levels, low hemoglobin and hematocrit (indicating anemia), and vitamin deficiencies.
Symptom expression of alcohol dependence may differ by culture and ethnicity, because people of different cultures may express physical and mental ailments differently. Ethnic and racial groups may respond differently to alcohol and medications used to treat alcohol dependence. Some groups may even enjoy greater protection against alcoholism as a result of their genetics. Certain ethnic groups may be more susceptible to alcoholism or related complications. For instance, vulnerability to cardiomyopathy and Wernicke-Korsakoff’s syndrome may be heritable and may vary by ethnicity. Latino men, for example, tend to show greater susceptibility to alcohol-related liver damage than do white men.
Early alcohol exposure and its interaction with genetics may lead to problems in fetal and child development. Fetal alcohol syndrome
may result when a pregnant woman drinks even a moderate amount of alcohol. Exposure to alcohol in the womb can cause mild to severe facial and dental abnormalities, mental impairment, and bone and heart problems that become more obvious and problematic as the child grows. Vision, hearing, and attention problems are also common. Children of alcoholics also can have difficulties in learning, language, and temperament because of hereditary and environmental effects of growing up in an unstable home with an alcoholic parent. In sum, parents who drink may increase the likelihood that their children will develop alcoholism through both genetic and environmental factors.
Screening and Diagnosis
Various questionnaires are commonly used to screen a person for alcoholism. Questions typically ask about the amount of alcohol consumed, how often drinking occurs, how much time is spent thinking about drinking, if withdrawal occurs after stopping drinking, and effects of drinking on personal life and health. Most persons with alcoholism will deny having the disorder, and family and friends may be questioned to support the diagnosis. Alcohol dependence is rarely diagnosed in a routine office visit. Diagnosis typically follows after a major negative health or social event occurs, such as liver disease or a motor vehicle accident. After diagnosis, patients may be subgrouped into type-I or type-II alcoholism.
Alcoholism is considered a highly heritable condition. Heritability estimates range from 40 to 70 percent, as reported by V. Nieratscker, A. Batra, and A. J. Fallgatter in the Journal of Molecular Psychiatryin 2013. According to a 2012 twin study published in the journal Evidence-Based Mental Health, the incidence of alcoholism and heritability rates were similar for both sexes.
Treatment and Therapy
Three candidate genes for alcohol treatment response are OPRM1, HTT, and COMT. Currently, treatment for alcoholism includes the use of medications such as naltrexone (opioid antagonist), acamprosate (taurine analog), or disulfuram (alcohol deterrent). Whether persons will respond to a certain medication and how long they will abstain from alcohol use may vary based on genetic makeup. Psychotherapy and behavior modification are important parts of alcohol dependence treatment. Alcoholics Anonymous has a twelve-step support program for persons with alcohol dependence.
Continued study of the genes associated with different patterns of alcohol problems, protective genetic effects in populations with exceptionally low rates of alcoholism, and genetically based interventions (such as matching pharmacotherapies to different populations of individuals to forestall the development of the problem) are assured. The study of genetics and alcoholism is also likely to encourage growth in the field of ethnopharmacology, the study of how different therapeutic drugs differentially affect members of specific ethnic groups.
Prevention and Outcomes
The best way to prevent alcoholism is to avoid the use of alcohol. Alcoholism is associated with an increased risk of hepatitis, liver cancer, abuse of other substances (such as marijuana, cocaine, sedatives, and stimulants), sexually transmitted diseases and other infections, malnutrition, psychiatric illness, and premature death. Persons with alcohol dependence are more likely to gamble, smoke cigarettes, or engage in other risky behaviors.
The presence of alcohol in modern life may have genetic roots. Historically, it helped those who could tolerate its taste and effects to survive and be selected for when others who could not do so perished as a result of consuming contaminated water. Alcohol has a complex relationship to human life, and alcoholism will be studied for some time.
Bibliography
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National Institute on Alcohol Abuse and Alcoholism. "Epigenetics—A New Frontier for Alcohol Research." Alcohol Alert 86 (2013): n. pag. Web. 16 July 2014.
National Institute on Alcohol Abuse and Alcoholism. "The Genetics of Alcoholism." Alcohol Alert 84 (2012): n. pag. Web. 16 July 2014.
Nieratschker, Vanessa, Anil Batra, and Andreas J. Fallgatter. "Genetics and Epigenetics of Alcohol Dependence." Journal of Molecular Psychiatry 1.11 (2013): 1–6. PDF file.
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Strat, Yann L., Nicolas Ramoz, Gunter Schumann, and Philip Gorwood. “Molecular Genetics of Alcohol Dependence and Related Endophenotypes.” Current Genomics 9 (2008): 444–51. Print.
Young-Wolff, K. C., E. Chereji, and C. A. Prescott. "Heritability of Alcohol Dependence Is Similar in Women and Men." Evidence-Based Mental Health 15.3 (2012): 57. PDF file.
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