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Genetics and Alcoholism: Implications for Advanced Practice Psychiatric/Mental Health Nursing Rose M. Kutlenios This article uses the research findings on genetics and alcoholism as a basis for nursing practice. Alcoholism is a complex genetic disorder in which multiple genes and the environment interact and contribute to the disease process. Family, twin, and adoption studies have consistently shown the genetic influence on alcoholism. Animal and human studies are identifying biological and genetic markers for alcoholism. The results of these studies should direct nurses in assessing patients at risk, educating patients about the disease and the rationale for selected treatments, referring at-risk individuals to support groups, and using supportive therapy. Copyright © 1998 by W.B. Saunders Company
LCOHOLISM IS A disease with powerful negative effects that impact not only the individual afflicted but also society at large. Alcoholism is the third leading cause of death in the United States and often leads to other sequela, such as cirrhosis, which are also leading causes of death (Carson & Arnold, 1996). A significant number of automobile accidents, violent acts including murders, rapes, domestic violence, and suicide are committed by people using alcohol. The widespread effects of alcoholism necessitate its study with the goal of increasing treatment efficacy and thus reducing the cost to society. One of the promising research areas in biomedical science today is the focus on alcoholism and genetics. This article presents a brief overview of genetics, the results of genetic studies related to alcoholism, and the implications of these genetic studies for the psychiatric/mental health Advanced Practice Nurse (PMHAPN). This article therefore, shows how nursing practice strategies can be derived from
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From the Department of Nursing, Wheeling Jesuit University, Wheeling, W~. Address reprint requests to Rose M. Kutlenios, RN, PhD, CS, Department of Nursing, Wheeling Jesuit University, 316 Washington Ave, Wheeling, WV26003. Copyright © 1998 by W.B. Saunders Company
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biomedical research related to genetics and alcoholism. OVERVIEW OF GENETICS
Brief History of Genetics
Historically, the movement to study genetics was fueled by the conceptualizations of Charles Darwin and the works of Gregor Mendel in the midnineteenth century (Klug & Cummings, 1997). Darwin's theory of natural selection posited that organisms will survive if their heritable traits allow them to adapt to the environment. Over a long time these slight adaptations accumulated and resulted in the evolution of the human species. What was missing from Darwin's theory was the actual mode of heredity or genetic transmission. This gap in Darwin's theory was filled in by the works of Gregor Mendel, a monk who experimented with pea plants. One important law resulting from Mendel's research, the law of segregation, asserts that for each characteristic, there are two elements, one inherited from each parent (Plomin, DeFries, & McClearn, 1990). In today's terminology, Mendel's elements are called genes and the alternate form of the gene is an allele. Genes, comprised of DNA, are located on chromosomes found in cells. Mendelian genetics commonly refers to the inheritance of traits by single genes in
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either a dominant or a recessive pattern. In a dominant pattern, the trait is expressed in the presence of one gene; whereas in a recessive pattern, the trait is expressed only if both genes marking the trait are inherited (McClearn, 1993). Genotype refers to the specific genes present in an individual, and phenotype refers to the expression of the genes.
Molecular and Population Genetics Subsequent to the foundational work of Mendel, there has been an explosion in the study of genetics, leading to a variety of specialties relying on advanced technologies, mathematical tools for analysis, and sophisticated computer programs. Two of the specialities in which great strides have been made are molecular genetics and population genetics. Molecular genetics studies the structure and function of genes and has been especially useful in Mendelian disorders (single-gene disorders) in locating the disease gene on the chromosome, identifying the mutation causing the disease, cloning it, and producing the abnormal protein product of the disease. These techniques have led to the identification of the genes for cystic fibrosis, Huntington's disease, and Duchenne muscular dystrophy (Kaufmann, Johnson, & Pardes, 1996). Currently, a major genetic effort, the Human Genome Project, whose goal is to construct maps of the human genome identifying its 50,000 to 100,000 genes and providing a sequence of DNA (The National Human Genome Research Institute, 1997) is underway. In addition to molecular genetics, studies in population genetics have flourished using mathematical tools to analyze data from groups including the following designs, population studies, family studies, twin studies, adoption studies, and association studies (Moldin & Gottesman, 1995). Population studies examine the incidence and prevalence of diseases in the population. Family studies start with an affected person (proband) and then examine the rates of the disease in relatives. Twin studies compare the concordance rates between monozygotic twins, those who share the same genetic composition, and dizygotic twins, those whose genetic composition is similar to any sibling. Genetically transmitted diseases would have a higher concordance rate in monozygotic twins than in dizygotic twins. Adoption studies examine either affected individuals as probands and their adopted
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offspring or affected and unaffected adoptees as probands. One of the benefits of adoption studies is the ability to distinguish genetic from environmental factors. Association studies examine the association of disease markers with diseases. This is accomplished by comparing the frequency of the presence of the marker in affected persons with the frequency of the presence of the marker in unaffected persons either in the general population or in families. According to Hodge (1994) association tests " . . . determine whether the associated marker allele appears with the disease more often than expected by chance a l o n e . . . " (p. 320). Various quantitative methods, each with a separate goal, use data collected in family, twin, and adoption studies. These quantitative methods, of which the most common in genetic and alcoholism research is linkage analysis, require computers to handle the complexity of the data (Moldin & Gottesman, 1995). The goal of linkage analysis is to determine if a known genetic marker is located close to a disease susceptibility marker so that they cosegregate (are usually inherited together). By using pedigree data and applying the analytic tool, linkage analysis, the researcher may determine on what chromosome the disease is located. Devor (1994) explains the statistical indicator of the presence of linkage as the LOD score, which is " . . . the log of ratio of the likelihood of linkage and the likelihood of no linkage" (p. 1109). A LOD score of 3 or greater is evidence for linkage, and thus there would be strong evidence for the linkage of the genetic marker with the disease. RESULTS OF GENETIC STUDIES IN ALCOHOLISM
The Disease of Alcoholism Before the implications for genetics and alcoholism are discussed, a brief overview of the disease of alcoholism will be given. The American Psychiatric Association (1994) in DSM-IV lists the two disorders of alcohol use as alcohol dependence and alcohol abuse. The term alcoholism is not an accepted medical diagnosis, but is often used, even in the scientific literature, to connote both alcohol dependence and alcohol abuse. Alcohol dependence is a pattern of compulsive use despite adverse consequences and is characterized by physiological dependence on the drug alcohol. Symptoms of physiological dependence on alcohol are manifested by tolerance and/or withdrawal symp-
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toms. Individuals with alcohol dependence often desire or try unsuccessfully to reduce or eliminate alcohol consumption and frequently curtail important social or occupational activities because of alcohol use. The second alcohol use disorder, alcohol abuse, differs from alcohol dependence because the affected person does not exhibit compulsive behaviors, tolerance, or withdrawal symptoms. However, the symptoms of alcohol abuse do include continued use of alcohol despite repeated adverse consequences that may include failure to fulfill family, social, or work obligations, legal difficulties, and physical danger such as driving or operating machinery while under the influence of alcohol. Persons with alcohol abuse have persistent problems, such as arguments with family members and problems at work because of their continued abuse of alcohol. Alcohol dependence and alcohol abuse are quite different from alcohol use. According to the American Psychiatric Association (1994), as many as 90% of adult Americans have used alcohol and many of those have experienced an adverse consequence from their use. Most people learn from the event, do not repeat it, and therefore do not develop alcoholism.
Alcoholism, a Complex Genetic Disorder What intrigues researchers and clinicians alike is the desire to determine what distinguishes the alcoholic from the average person who can drink in moderation, so that the disease can be prevented and treated. Results from genetic studies seem to hold a part of the key to solving the riddle. The genetic influences on alcoholism are not as easy to determine as was the case with cystic fibrosis or Huntington's disease. Unlike cystic fibrosis and Huntington's disease, which follow the Mendelian patterns of inheritance, alcoholism is thought to be a complex disorder as are most psychiatric disorders. Complex disorders are thought to be caused by a variety of factors and are not caused by a single gene disorder as is the case with Mendelian disorders. Complex disorders such as alcoholism push the limits of traditional molecular genetics and population genetics. The National Human Genome Research Institute (1997) lists four factors that make determining genetic influences in complex disorders difficult. The first factor is that many complex disorders such as alcoholism can occur solely from environmental factors with no genetic influence. The second factor is that complex disor-
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ders are not homogeneous; alcoholism is not one distinct disease. It is diagnosed based not on it etiological origin but on its behavioral symptoms. The third factor is that complex disorders are almost always caused by more than one gene, may involve the interaction of genes, and are impacted by environmental factors. The fourth factor is that inheriting a gene mutation does not necessarily lead to the development of the disease. However, the gene might also lead to a range of symptoms from mild to moderate impacted by other genes and environmental factors. In addition, Comings (1997) explains that single gene disorders are rare and that a single gene explains 95% to 100% of the variance in terms of whether the disease is present. On the other hand, complex disorders are common, may require the presence of five or more genes, and each gene explains only 1% to 10% of the variance regarding a spectrum of disorders. According to the National Human Genome Research Institute (1997), some examples of complex disorders in addition to alcoholism include Alzheimer's disease, autism, colon cancer, coronary artery disease, diabetes, hypertension, obesity, obsessive compulsive disorder, schizophrenia, and tourette syndrome. The research related to the genetic implications of alcoholism has been fraught with all the difficulties inherent in studying complex diseases. Even though observations of alcoholism running in families has been noted as far back as the Greek philosopher Aristotle (Noble, 1996), there is still no scientific consensus on the exact nature of the role of genetics in alcoholism. However, research does implicate genetics as an important influence in the development of alcoholism, and according to Anderson (1994), having a first-degree relative with alcoholism is a good predictor of the risk for the development of alcoholism. The risk of developing alcoholism in males who have a biological parent with alcoholism seems to be greater than the risk in females. In such situations, males have a four times greater risk than do other males with no alcoholic parent, whereas, females have a three times greater risk than do other females with no alcoholic parent (Blum, Sheridan, Chert, Wood, Braverman, Cull, & Comings, 1997).
Twin and Adoption Studies Twin and adoption studies gave early credence to the relevance of genetic influence in alcoholism. Even though the first studies were not conducted
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until the 1970s and there have been few large-scale twin and adoption studies, their results have been rather consistent in that adopted children of alcoholics have a higher risk than do other adopted children and that monozygotic twins have a higher concordance rate of alcoholism than do dizygotic twins. In a meta-analysis of twin and adoptive studies, Heath (1995) concluded that the importance of genetics in alcoholism has been consistent despite the time range for twins born anywhere from the 1920s to the 1960s and the differences in sampling methods and in diagnostic criteria used in determining alcoholism. Genetic Markers
Because the evidence supporting genetic influence from family, twin, and adoption studies has been strong, researchers have moved to trying to find the phenotypic markers and the putative genes implicated in alcoholism. A large number of studies using both animal and human models have been conducted. Animal studies use rodents, mice, or rats that are selectively bred for their responses to alcohol, such as alcohol preference and alcohol sensitivity. Phillips and Crabbe (1991) in a review of hundreds of rodent studies reported that most studies conclude that alcoholism is influenced by both polygenetic (more than one gene) and environmental factors and that alcohol preference can be altered in some inbred strains by the method of handling of the rodents. That rodents can be bred for their preference for alcohol supports the genetic influence. That alcohol preference can be altered by methods of handling the rodents supports the environmental influence. Other studies compare various physiological characteristics in rodents bred for opposite traits, such as either high or low sensitivity to alcohol. Of particular interest is the difference in various neurochemicals in these rodent lines. Consistent findings across many studies reported by Allan and Hand s (1991) are that alcohol preference is associated with low levels of brain serotonin and that there are genetic differences in the processing of endorphin peptides. This latter finding that rodents with preferences to alcohol show an increased response of the opioid system (endorphin peptides) to alcohol has led the way to the use of an opioid antagonist in treatment of alcoholism, the discussion of which will be later in this article (Froehlich, 1995). Cun'ently, strategies are also underway to map quantitative trait loci in
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mice strains bred for alcohol sensitivity (Buck, 1995). Rodent studies can provide fertile groundwork for laying the foundation of human studies especially from the linkage homology between mice and humans. Studies in humans thus far point to two promising areas in the study of alcoholism and genetic markers. These include genetic influences on the dopaminergic system and on aldehyde dehydrogenase (ALDH). The first genetic influence seems to increase the risk for alcoholism, whereas ALDH seems to decrease the risk. In terms of the dopaminergic system, a frequently studied gene in regards to alcoholism is the A1 allele of the dopamine D2 receptor gene (DRD2). Results of studies on this genetic factor have been contradictory mainly because of the difficulty of finding the best model for studying alcoholism, a complex disorder. Because many of the statistical tools used in traditional genetics rely on assumptions such as single-gene inheritance that complex disorders do not meet, their application to complex disorders has led to disappointing and contradictory results. Linkage analysis applied to alcoholism has been an example of this disappointment (Devor, 1994). Although association studies implicate this DRD2 gene, linkage analysis techniques have not. In a review of DRD2 studies (Blum et al., 1997), an explanation given for the failure of linkage analysis is that in computer simulations with disorders caused by four or more genes, the LOD scores were found to be negative even though association studies showed the marker to be significant. Several researchers (Blum et al., 1997; Devor, 1994; Hodge, 1994) favor the use of association studies over linkage analysis for complex disorders when the influence of any one given gene is not strong. Noble (1996) began studying the DRD2 gene by using DNA probes on the brains of 35 deceased, severe alcoholics and 35 nonalcoholics. The DRD2 gene was the only probe associated with alcoholism. Since then the A1 allele of the DRD2 gene has been associated with alcoholism in a variety of other studies across large samples. However, according to Blum et al. (1997) it is not associated with all forms of alcoholism but is most often associated with severe alcoholism. Further tests were performed to examine the expression of the A1 allele of the DRD2 gene in subjects. Noble (1996) reported that subjects with this gene had 30% fewer
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D2 binding sites and certain electrical activity changes related to information processing. The other interesting finding with this gene is that it is not specific for alcoholism in that it is associated with a variety of other disorders such as obesity with carbohydrate craving, pathological gambling, smoking, and other substance abuse (Blum et al, 1997). A mutation of the ALDH2 gene has been studied and repeatedly shown to reduce the risk of alcoholism in those who have it. ALDH is an enzyme that oxidizes acetaldehyde, a product of alcohol metabolism in the liver. People who have the mutated ALDH2 gene have a decreased ability to rid the body of acetaldehyde resulting in the uncomfortable symptoms of facial flushing, headache, and nausea with the consumption of alcohol (Devor, 1994). The protective gene is more common in people of Asian descent although it can be found in other ethnic groups. A study by Wall, Thomasson, and Ehlers (1996) showed the presence of varying symptom responses to an alcohol challenge in 50 Asian-American men who were genotyped for the different ALDH2 alleles. Other studies are in progress to unravel the genetic and environmental influences in alcoholism. One such study is the Collaborative Study on the Genetics of Alcoholism (COGA) as reported by Schuckit, Tsuang, Anthenelli, Tipp, and Nurnberger (1996). One factor that this study is addressing that may be associated with the later development of alcoholism is the level of reaction to alcohol challenges. In this study, the cortisol levels in response to an alcohol challenge were compared in sons of alcoholics and in matched controls. Results showed that the sons of alcoholics had a lower response to alcohol. In another part of COGA, Schuckit and Smith (1996) in an 8-year longitudinal study compared the rates of alcohol dependence and alcohol abuse in sons of alcoholics with those rates in a control group. None of the subjects had an alcohol disorder at the onset of the study. Results showed 8 years later that the sons of alcoholics had double the rates of both dependence and abuse as did the control group. Furthermore, having a low level of reaction to alcohol challenges at the beginning of the study was associated with actually developing alcoholism 8 years later. Ongoing portions of COGA hope to use some of these findings to direct molecular genetic studies. Another biological factor that has been associ-
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ated with alcoholism in repeated studies is the decreased activity of the enzyme monoamine oxidase (MAO), particularly the type MAOB (Devor, 1994). The results of a study by Devor, Abell, Hoffman, Tabakoff, and Clonninger (1994) show that decreased platelet MAOB activity is a marker for increased risk of alcoholism and that families in which alcoholism follows a particular course have a higher loading for this genetic risk. In these families, the alcoholism has an earlier onset, does not respond as well to treatment, has a higher comorbidity for disorders such as antisocial personality disorder, and is more prevalent in males. However, the impact of decreased MAOB activity on alcoholic behavior is not known or is its relevance to treatment known. Research on MAOB shows another area where future results may open doors for treatment options. IMPLICATIONS FOR THE PSYCHIATRIC/MENTAL HEALTH ADVANCED PRACTICE NURSE
The ultimate goal of the collective results of the preceding studies on genetics and alcoholism should be to lead to methods for the prevention and treatment of alcoholism. In terms of this goal, research is still in its infancy. A time in the future might be envisioned when all the genetic and environmental factors are sorted out so that these risk factors could be targeted for preventative programs. A time might also be envisioned when any given alcoholic could be genotyped so that interventions could be geared toward that person's specific physiological impairments. However, that time is not here. It is important for the nurse practitioner to examine the current findings for their utility in nursing practice. A known fact is that alcoholism is more prevalent in children of alcoholics. PMHAPNs can use this knowledge to treat the whole family, not just the alcoholic. Family members can be referred to groups analogous to Alcoholics Anonymous for the alcoholic, such as AL-ANON for the significant others, Adult Children of Alcoholics (ACOA) for adult children of alcoholics, and Alateen for teenage children of alcoholics. Many family members of alcoholics suffer from the stress of living with an alcoholic and try unsuccessfully to control the alcoholic's drinking. The above support groups use a modification of the twelve steps of Alcoholics Anonymous to teach family members that they are
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powerless over the alcoholic's drinking and that they need not be controlled by it. These support groups can help at-risk individuals learn how to cope with their own lives, and provide social support, which is a health-promoting factor, and thus reduce environmental risk factors. It is also important for the PMHAPN to use the knowledge that having a frst-degree relative with alcoholism is a predictor of increased risk for alcoholism. People at risk should be educated to the idea that they may be at greater risk for the development of alcoholism so that they can modify their environments to possibly reduce this risk. They need to know that increased risk does not mean that they are going to be an alcoholic; it does mean that the person may have a predisposition to this behavior if the person develops an alcoholic lifestyle. A person at risk can learn not to choose friends who drink excessively and to avoid using alcohol to numb unacceptable feelings or as a reward. A susceptible person can learn to accept responsibility for life choices. Family history of alcoholism should be part of the family history section of the nursing assessment in any patient along with the person's own alcohol use. A positive family history might alert the nurse to be more sensitive to assessing for alcohol abuse and genetically related disorders such as carbohydrate-craving obesity, gambling, and other substance abuse. Knowledge that the A1 allele of the DRD2 gene is associated with this particular spectrum of disorders provides the rationale for broadening the assessment beyond drinking behaviors. Early detection through a thorough nursing assessment can result in an earlier treatment and perhaps a better prognosis than delayed treatment would. This same research on the DRD2 gene might be useful in supportive therapy. If people with this gene have less of these dopamine receptors and, therefore, less ability to stimulate their pleasure centers, perhaps they could be taught other ways to release natural endorphins, such as physical activity. Perhaps a regular aerobic routine would prove beneficial, and its efficacy could be tested through clinical research. Results from the rodent studies related to the differing processing mechanisms of endorphin peptides have led to the treatment of alcohol recovery with an opiate antagonist Naltrexone (DupontPharma Co., Wilmington, DE). It is hypothesized that alcoholics metabolize alcohol differently so
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that more powerful opiate-like substances called endorphin peptides are formed and serve as powerful reinforcers of alcohol. Naltrexone blocks the effects of the endorphin and seems to reduce cravings in recovering alcoholics. According to a commentary by Gordis (1996), the combination of Naltrexone and counseling extended the time to the first drink and reduced the number of binge-type relapses in recovering alcoholics. This same information about the differing endorphin-processing mechanisms in alcoholics could be useful in the education of alcoholics. Often people with alcohol abuse problems have difficulty accepting the idea that they must be abstinent and think they can teach themselves to drink in moderation. The research pointing to a more powerful reinforcing opiate-like substance in the alcoholic who drinks could provide useful knowledge to help explain to the alcoholic why drinking in moderation is more than an issue of willpower. The PMHAPN can explain to patients with alcoholism how drinking in moderation to them may be similar to using heroin in moderation. Most people understand that heroin is a powerfully addictive drug, and this analogy might, therefore, prove a useful one for the alcoholic. An interesting observation about the protective nature of one specific allele of the ALDH2 gene is that this gene functions in the same manner as the drug disulfiram (Antabuse [Wyeth-Ayerst Laboratories, Philadelphia, PAl) that is sometimes used to help alcoholics maintain sobriety. Disulfiram inhibits ALDH thus blocking the metabolism of acetaldehyde, a product of alcohol metabolism (Townsend, 1995). The accumulation of acetaldehyde leads to uncomfortable reactions in the person on disulfiram who ingests alcohol just as it does in the person with the specific allele of the ALDH2 gene. One difference is that in the person on disulfiram, the reactions can be life threatening because of the very high accumulation of acetaldehyde. Perhaps, as part of the education of the patient prescribed disulfiram, the nurse can explain that a few people have a protective mechanism similar to that provided by the drug disulfiram. This explanation might help the person see this treatment as logical. The nurse can also use the growing body of knowledge on the genetic basis of alcoholism in both supportive therapy and community education targeted toward the nature of alcohol use disorders. These disorders have both a genetic and an environ-
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mental basis. The genetic basis supports the disease model of alcoholism that is in opposition to the model that purports it to be a moral problem or one of a character weakness. In supportive therapy the nurse can use the disease model to reinforce that alcoholism is a treatable disease and not a curable disease as are many chronic illnesses thought to also be complex genetic disorders such as hypertension and diabetes. Lifestyle changes can impact the progression of alcoholism just as they can impact the progression of hypertension and diabetes. This kind of knowledge can help the alcoholic better understand the disease and why lifelong compliance to treatment is advisable. Because alcoholism is a genetic disorder, the nurse might think of the possibility of genetic counseling. Other than educating children of alcoholics that they may be at a greater risk for developing alcoholism, there is no current advisable role for genetic counseling in relation to alcoholism. A significant principle of genetic counseling is that it is provided only on request, and the biggest constraint to genetic counseling related to alcoholism is the inability to provide even the most basic information such as the individual's specific risk (Hall, 1996). For diseases in which genetic counseling is appropriate, it is possible to do a test and provide an individualized assessment of recurrence risk. This is not possible for alcoholism. Another problem is that there is a combination of genetic and environmental factors in alcoholism, and it may be more important for an individual to know the environmental risks that can be manipulated than to know the genetic risks. Still another problem is that alcoholism is a disease with a late onset. Even if the recurrence risk at some future time could be predicted, what benefit would this knowledge provide? Unless there were a preventable treatment, the information to the person would not be very useful and might be harmful in terms of being a social stigma and possibly increasing insurance liability. The ethical implications would be enormous. The Committee on Assessing Genetic Risks (Andrews, Fullarton, Holtzman, & Motulsky, 1994, p. 106) " . . . recommends that, if predictive tests for mental disorders become a reality, results must be handled with stringent attention to protect an already vulnerable population." The committee also recommended expanding the graduate curriculum of nurses to include genetic counseling because health care practitioners, including nurses,
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are not sufficiently educated to provide this service, which might be frequently requested as genetic knowledge explodes and more specific tests become available. In summary, research supports that alcoholism is a complex genetic disorder with both multiple genetic and environmental influences. The literature reports much controversy over the appropriate designs and analytical tools with which to study the genetic influences of alcoholism. Research suggests that genetic markers may be associated with the varying types of the disorder and the severity of the disorders. Some of the markers that have repeated studies implicating them are the A1 allele of the DRD2 gene and a specific allele of the ALDH2 gene. In rodent studies there are differences in endorphin peptide processing in response to alcohol in some rodent strains. The P M H A P N can use the results of genetic research to assess and educate patients about the disease and the rationale for selected treatments, to refer at-risk individuals to support groups, and for supportive therapy. Genetic counseling based on any specificity of individual risk is not currently available, and nurses who may eventually become involved in this area should become educated to interpret future tests, provide genetic counseling, and be cognizant of the multiple inherent ethical implications.
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Allan, A.M. & Harris, R.A. (1991). Neurochemical studies of genetic differences in alcohol action. In J.C. Crabbe & R.A. Harris (Eds.). The genetic basis of alcohol and drug actions (pp. 105-152). New York, NY, Plenum. American PsychiatricAssociation. (1994). Diagnostic and statistical manual of mental disorders (4th ed.). Washington, DC, American Psychiatric Association. Anderson, V.E. (1994). Genes, behavior, and responsibility: Research perspectives. In M.S. Frankel & A.H. Teich (Eds.), The genetic frontier: Ethics, law, and policy (pp. 105-130). Washington, DC, American Association for the Advancement of Science. Andrews, L.B., Fullarton, J.E., Holzman, N.A., & Motulsky, A.G. (Eds.). (1994). Assessing genetic risks: Implications for health and social policy. Washington, DC: National Academy. Blum, L., Sheridan, RJ., Chert, C.H., Wood, R.C., Braverman, E.R., Cull, J.G., & Comings, D.E. (1997). The dopamine D2 receptor gene locus in reward deficiency syndrome: Meta-analysis. In K. Blum & E.R Noble (Eds.), Handbook of psychiatric genetics (pp. 407-432). New York, NY, CRC Press. Buck, K.J. (1995). Strategies for mapping and identifying quantitative trait loci specifying behavioral responses to
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alcohol. Alcoholism: Clinical and Experimental Research, 19(4), 795-801. Carson, V.B. & Arnold, E.N. (1996). The journey anesthetized by substance use. Mental health nursing: The nursepatient journey (pp. 793-839). Philadelphia, PA, Saunders. Comings, D.E. (1997). Polygenetie inheritance in psychiatric disorders. In K. Blum & E.R Noble (Eds.), Handbook of psychiatric genetics (pp. 235-260). New York, NY, CRC Press. Devor, E.J. (1994). A developmental-genetic model of alcoholism: Implications for genetic research. Journal of Consulting and Clinical Psychology, 62(6), 1108-1115. Devor, E.J., Abell, C.W., Hoffman, EL., Tabakoff, B., & Cloninger, C.R. (1994). Platelet M A t activity in type I and type II alcoholism. In T.E Babor, V. Heselbrock, R.E. Meyer, & W. Shoemaker (Eds.), Types of alcoholics: Evidence from clinical experimental, and genetic research (pp. 119-128). New York, NY, New York Academy of Sciences. Froehlich, J.C. (1995). Genetic factors in alcohol selfadministration. Journal of Clinical Psychiatry, 56 (supp 7), 15-23. Gordis, E. (1996). Alcohol research. Archives of General Psychiatry, 53(3), 199-201. Hall, L.L. (1996). The human implications of psychiatric genetics. In L.L. Hall (Ed.), Genetics and mental illness: Evolving issues for research and society (pp. 157-188). New York, NY, Plenum. Heath, A.C. (1995). Genetic influences on alcoholism risk: A review of adoption and twin studies. Alcohol Health & Research World, 19(3), 166-171. Hodge, S.E. (1994). What association analysis can and cannot tell us about the genetics of complex disease. American Journal of Medical Genetics, 54(4), 318-323. Kaufmann, C.A., Johnson, J.E., & Pardes, H. (1996). Evolution and revolution in psychiatric genetics. In L.L. Hall (Ed.),
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Genetics and mental illness: Evolving issues for research and society. (pp. 5-28). New York, NY, Plenum. Klug, W.S. & Cummings, M.R. (1997). Concepts of genetics (5th ed.). Upper Saddle River, NJ, Prentice Hall. McClearn, G.E. (1993). Behavioral genetics: The last century and the next. In R. Plomin & G.E. McClearn (Eds.), Nature nurture & psychology (pp. 27-51). Washington, DC, American Psychological Association. Moldin, S.O. & Gottesman, I.I. (1995). Population genetics in psychiatry. In H.I. Kaplan & B.J. Sadock (Eds.), Comprehensive textbook of psychiatry/Vl." Vol. 1 (6th ed., pp. 144-155). Baltimore, MD, Williams & Wilkens. The National Human Genome Research Institute (1997). The human genome project [On-line]. Available: http:// www.nhgri.nih.gov/HGP/. Noble, E.R (1996). The gene the rewards alcoholism. Scientific American: Science & Medicine, 3(2), 52-61. Phillips, T.J. & Crabbe, J.C. (1991). Behavioral studies of genetic differences in alcohol action. In J.C. Crabbe & R.A. Harris (Eds.), The genetic basis of alcohol and drug actions (pp. 25-104). New York, NY, Plenum. Plomin, R., DeFiles, J.C., & McClearn, G.E. (1990). Behavioral genetics: A primer (2nd ed.). New York, NY, Freeman. Schuckit, M.A. & Smith, T.L (1996). An 8-year follow-up of 450 sons of alcoholic and control subjects. Archives of General Psychiatry, 53(3), 202-210. Schuckit, M.A., Tsuang, J.W., Anthenelli, R.M., Tipp, J.E., & Nurnberger, J.I. (1996). Alcohol challenges in young men from alcoholic pedigrees and control families: A report from the COGA project. Journal of the Studies of Alcohol 57(4), 368-377. Townsend, M.C. (1995). Drug guide for psychiatric nursing (2nd ed.). Philadelphia, PA, Davis. Wall, T.L., Thomasson, H.R., & Ehlers, C.L. (1996). Investigatorobserved alcohol-indnced flushing but not self-report of flushing is a valid predictor of ALDH2 genotype. Journal of the Studies of Alcohol, 57(3), 267-272.
LCOHOLISM IS A disease with powerful negative effects that impact not only the individual afflicted but also society at large. Alcoholism is the third leading cause of death in the United States and often leads to other sequela, such as cirrhosis, which are also leading causes of death (Carson & Arnold, 1996). A significant number of automobile accidents, violent acts including murders, rapes, domestic violence, and suicide are committed by people using alcohol. The widespread effects of alcoholism necessitate its study with the goal of increasing treatment efficacy and thus reducing the cost to society. One of the promising research areas in biomedical science today is the focus on alcoholism and genetics. This article presents a brief overview of genetics, the results of genetic studies related to alcoholism, and the implications of these genetic studies for the psychiatric/mental health Advanced Practice Nurse (PMHAPN). This article therefore, shows how nursing practice strategies can be derived from
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From the Department of Nursing, Wheeling Jesuit University, Wheeling, W~. Address reprint requests to Rose M. Kutlenios, RN, PhD, CS, Department of Nursing, Wheeling Jesuit University, 316 Washington Ave, Wheeling, WV26003. Copyright © 1998 by W.B. Saunders Company
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biomedical research related to genetics and alcoholism. OVERVIEW OF GENETICS
Brief History of Genetics
Historically, the movement to study genetics was fueled by the conceptualizations of Charles Darwin and the works of Gregor Mendel in the midnineteenth century (Klug & Cummings, 1997). Darwin's theory of natural selection posited that organisms will survive if their heritable traits allow them to adapt to the environment. Over a long time these slight adaptations accumulated and resulted in the evolution of the human species. What was missing from Darwin's theory was the actual mode of heredity or genetic transmission. This gap in Darwin's theory was filled in by the works of Gregor Mendel, a monk who experimented with pea plants. One important law resulting from Mendel's research, the law of segregation, asserts that for each characteristic, there are two elements, one inherited from each parent (Plomin, DeFries, & McClearn, 1990). In today's terminology, Mendel's elements are called genes and the alternate form of the gene is an allele. Genes, comprised of DNA, are located on chromosomes found in cells. Mendelian genetics commonly refers to the inheritance of traits by single genes in
Archives of Psychiatric Nursing, Vol.Xll, No. 3 (June), 1998: pp 154-161
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either a dominant or a recessive pattern. In a dominant pattern, the trait is expressed in the presence of one gene; whereas in a recessive pattern, the trait is expressed only if both genes marking the trait are inherited (McClearn, 1993). Genotype refers to the specific genes present in an individual, and phenotype refers to the expression of the genes.
Molecular and Population Genetics Subsequent to the foundational work of Mendel, there has been an explosion in the study of genetics, leading to a variety of specialties relying on advanced technologies, mathematical tools for analysis, and sophisticated computer programs. Two of the specialities in which great strides have been made are molecular genetics and population genetics. Molecular genetics studies the structure and function of genes and has been especially useful in Mendelian disorders (single-gene disorders) in locating the disease gene on the chromosome, identifying the mutation causing the disease, cloning it, and producing the abnormal protein product of the disease. These techniques have led to the identification of the genes for cystic fibrosis, Huntington's disease, and Duchenne muscular dystrophy (Kaufmann, Johnson, & Pardes, 1996). Currently, a major genetic effort, the Human Genome Project, whose goal is to construct maps of the human genome identifying its 50,000 to 100,000 genes and providing a sequence of DNA (The National Human Genome Research Institute, 1997) is underway. In addition to molecular genetics, studies in population genetics have flourished using mathematical tools to analyze data from groups including the following designs, population studies, family studies, twin studies, adoption studies, and association studies (Moldin & Gottesman, 1995). Population studies examine the incidence and prevalence of diseases in the population. Family studies start with an affected person (proband) and then examine the rates of the disease in relatives. Twin studies compare the concordance rates between monozygotic twins, those who share the same genetic composition, and dizygotic twins, those whose genetic composition is similar to any sibling. Genetically transmitted diseases would have a higher concordance rate in monozygotic twins than in dizygotic twins. Adoption studies examine either affected individuals as probands and their adopted
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offspring or affected and unaffected adoptees as probands. One of the benefits of adoption studies is the ability to distinguish genetic from environmental factors. Association studies examine the association of disease markers with diseases. This is accomplished by comparing the frequency of the presence of the marker in affected persons with the frequency of the presence of the marker in unaffected persons either in the general population or in families. According to Hodge (1994) association tests " . . . determine whether the associated marker allele appears with the disease more often than expected by chance a l o n e . . . " (p. 320). Various quantitative methods, each with a separate goal, use data collected in family, twin, and adoption studies. These quantitative methods, of which the most common in genetic and alcoholism research is linkage analysis, require computers to handle the complexity of the data (Moldin & Gottesman, 1995). The goal of linkage analysis is to determine if a known genetic marker is located close to a disease susceptibility marker so that they cosegregate (are usually inherited together). By using pedigree data and applying the analytic tool, linkage analysis, the researcher may determine on what chromosome the disease is located. Devor (1994) explains the statistical indicator of the presence of linkage as the LOD score, which is " . . . the log of ratio of the likelihood of linkage and the likelihood of no linkage" (p. 1109). A LOD score of 3 or greater is evidence for linkage, and thus there would be strong evidence for the linkage of the genetic marker with the disease. RESULTS OF GENETIC STUDIES IN ALCOHOLISM
The Disease of Alcoholism Before the implications for genetics and alcoholism are discussed, a brief overview of the disease of alcoholism will be given. The American Psychiatric Association (1994) in DSM-IV lists the two disorders of alcohol use as alcohol dependence and alcohol abuse. The term alcoholism is not an accepted medical diagnosis, but is often used, even in the scientific literature, to connote both alcohol dependence and alcohol abuse. Alcohol dependence is a pattern of compulsive use despite adverse consequences and is characterized by physiological dependence on the drug alcohol. Symptoms of physiological dependence on alcohol are manifested by tolerance and/or withdrawal symp-
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toms. Individuals with alcohol dependence often desire or try unsuccessfully to reduce or eliminate alcohol consumption and frequently curtail important social or occupational activities because of alcohol use. The second alcohol use disorder, alcohol abuse, differs from alcohol dependence because the affected person does not exhibit compulsive behaviors, tolerance, or withdrawal symptoms. However, the symptoms of alcohol abuse do include continued use of alcohol despite repeated adverse consequences that may include failure to fulfill family, social, or work obligations, legal difficulties, and physical danger such as driving or operating machinery while under the influence of alcohol. Persons with alcohol abuse have persistent problems, such as arguments with family members and problems at work because of their continued abuse of alcohol. Alcohol dependence and alcohol abuse are quite different from alcohol use. According to the American Psychiatric Association (1994), as many as 90% of adult Americans have used alcohol and many of those have experienced an adverse consequence from their use. Most people learn from the event, do not repeat it, and therefore do not develop alcoholism.
Alcoholism, a Complex Genetic Disorder What intrigues researchers and clinicians alike is the desire to determine what distinguishes the alcoholic from the average person who can drink in moderation, so that the disease can be prevented and treated. Results from genetic studies seem to hold a part of the key to solving the riddle. The genetic influences on alcoholism are not as easy to determine as was the case with cystic fibrosis or Huntington's disease. Unlike cystic fibrosis and Huntington's disease, which follow the Mendelian patterns of inheritance, alcoholism is thought to be a complex disorder as are most psychiatric disorders. Complex disorders are thought to be caused by a variety of factors and are not caused by a single gene disorder as is the case with Mendelian disorders. Complex disorders such as alcoholism push the limits of traditional molecular genetics and population genetics. The National Human Genome Research Institute (1997) lists four factors that make determining genetic influences in complex disorders difficult. The first factor is that many complex disorders such as alcoholism can occur solely from environmental factors with no genetic influence. The second factor is that complex disor-
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ders are not homogeneous; alcoholism is not one distinct disease. It is diagnosed based not on it etiological origin but on its behavioral symptoms. The third factor is that complex disorders are almost always caused by more than one gene, may involve the interaction of genes, and are impacted by environmental factors. The fourth factor is that inheriting a gene mutation does not necessarily lead to the development of the disease. However, the gene might also lead to a range of symptoms from mild to moderate impacted by other genes and environmental factors. In addition, Comings (1997) explains that single gene disorders are rare and that a single gene explains 95% to 100% of the variance in terms of whether the disease is present. On the other hand, complex disorders are common, may require the presence of five or more genes, and each gene explains only 1% to 10% of the variance regarding a spectrum of disorders. According to the National Human Genome Research Institute (1997), some examples of complex disorders in addition to alcoholism include Alzheimer's disease, autism, colon cancer, coronary artery disease, diabetes, hypertension, obesity, obsessive compulsive disorder, schizophrenia, and tourette syndrome. The research related to the genetic implications of alcoholism has been fraught with all the difficulties inherent in studying complex diseases. Even though observations of alcoholism running in families has been noted as far back as the Greek philosopher Aristotle (Noble, 1996), there is still no scientific consensus on the exact nature of the role of genetics in alcoholism. However, research does implicate genetics as an important influence in the development of alcoholism, and according to Anderson (1994), having a first-degree relative with alcoholism is a good predictor of the risk for the development of alcoholism. The risk of developing alcoholism in males who have a biological parent with alcoholism seems to be greater than the risk in females. In such situations, males have a four times greater risk than do other males with no alcoholic parent, whereas, females have a three times greater risk than do other females with no alcoholic parent (Blum, Sheridan, Chert, Wood, Braverman, Cull, & Comings, 1997).
Twin and Adoption Studies Twin and adoption studies gave early credence to the relevance of genetic influence in alcoholism. Even though the first studies were not conducted
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until the 1970s and there have been few large-scale twin and adoption studies, their results have been rather consistent in that adopted children of alcoholics have a higher risk than do other adopted children and that monozygotic twins have a higher concordance rate of alcoholism than do dizygotic twins. In a meta-analysis of twin and adoptive studies, Heath (1995) concluded that the importance of genetics in alcoholism has been consistent despite the time range for twins born anywhere from the 1920s to the 1960s and the differences in sampling methods and in diagnostic criteria used in determining alcoholism. Genetic Markers
Because the evidence supporting genetic influence from family, twin, and adoption studies has been strong, researchers have moved to trying to find the phenotypic markers and the putative genes implicated in alcoholism. A large number of studies using both animal and human models have been conducted. Animal studies use rodents, mice, or rats that are selectively bred for their responses to alcohol, such as alcohol preference and alcohol sensitivity. Phillips and Crabbe (1991) in a review of hundreds of rodent studies reported that most studies conclude that alcoholism is influenced by both polygenetic (more than one gene) and environmental factors and that alcohol preference can be altered in some inbred strains by the method of handling of the rodents. That rodents can be bred for their preference for alcohol supports the genetic influence. That alcohol preference can be altered by methods of handling the rodents supports the environmental influence. Other studies compare various physiological characteristics in rodents bred for opposite traits, such as either high or low sensitivity to alcohol. Of particular interest is the difference in various neurochemicals in these rodent lines. Consistent findings across many studies reported by Allan and Hand s (1991) are that alcohol preference is associated with low levels of brain serotonin and that there are genetic differences in the processing of endorphin peptides. This latter finding that rodents with preferences to alcohol show an increased response of the opioid system (endorphin peptides) to alcohol has led the way to the use of an opioid antagonist in treatment of alcoholism, the discussion of which will be later in this article (Froehlich, 1995). Cun'ently, strategies are also underway to map quantitative trait loci in
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mice strains bred for alcohol sensitivity (Buck, 1995). Rodent studies can provide fertile groundwork for laying the foundation of human studies especially from the linkage homology between mice and humans. Studies in humans thus far point to two promising areas in the study of alcoholism and genetic markers. These include genetic influences on the dopaminergic system and on aldehyde dehydrogenase (ALDH). The first genetic influence seems to increase the risk for alcoholism, whereas ALDH seems to decrease the risk. In terms of the dopaminergic system, a frequently studied gene in regards to alcoholism is the A1 allele of the dopamine D2 receptor gene (DRD2). Results of studies on this genetic factor have been contradictory mainly because of the difficulty of finding the best model for studying alcoholism, a complex disorder. Because many of the statistical tools used in traditional genetics rely on assumptions such as single-gene inheritance that complex disorders do not meet, their application to complex disorders has led to disappointing and contradictory results. Linkage analysis applied to alcoholism has been an example of this disappointment (Devor, 1994). Although association studies implicate this DRD2 gene, linkage analysis techniques have not. In a review of DRD2 studies (Blum et al., 1997), an explanation given for the failure of linkage analysis is that in computer simulations with disorders caused by four or more genes, the LOD scores were found to be negative even though association studies showed the marker to be significant. Several researchers (Blum et al., 1997; Devor, 1994; Hodge, 1994) favor the use of association studies over linkage analysis for complex disorders when the influence of any one given gene is not strong. Noble (1996) began studying the DRD2 gene by using DNA probes on the brains of 35 deceased, severe alcoholics and 35 nonalcoholics. The DRD2 gene was the only probe associated with alcoholism. Since then the A1 allele of the DRD2 gene has been associated with alcoholism in a variety of other studies across large samples. However, according to Blum et al. (1997) it is not associated with all forms of alcoholism but is most often associated with severe alcoholism. Further tests were performed to examine the expression of the A1 allele of the DRD2 gene in subjects. Noble (1996) reported that subjects with this gene had 30% fewer
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D2 binding sites and certain electrical activity changes related to information processing. The other interesting finding with this gene is that it is not specific for alcoholism in that it is associated with a variety of other disorders such as obesity with carbohydrate craving, pathological gambling, smoking, and other substance abuse (Blum et al, 1997). A mutation of the ALDH2 gene has been studied and repeatedly shown to reduce the risk of alcoholism in those who have it. ALDH is an enzyme that oxidizes acetaldehyde, a product of alcohol metabolism in the liver. People who have the mutated ALDH2 gene have a decreased ability to rid the body of acetaldehyde resulting in the uncomfortable symptoms of facial flushing, headache, and nausea with the consumption of alcohol (Devor, 1994). The protective gene is more common in people of Asian descent although it can be found in other ethnic groups. A study by Wall, Thomasson, and Ehlers (1996) showed the presence of varying symptom responses to an alcohol challenge in 50 Asian-American men who were genotyped for the different ALDH2 alleles. Other studies are in progress to unravel the genetic and environmental influences in alcoholism. One such study is the Collaborative Study on the Genetics of Alcoholism (COGA) as reported by Schuckit, Tsuang, Anthenelli, Tipp, and Nurnberger (1996). One factor that this study is addressing that may be associated with the later development of alcoholism is the level of reaction to alcohol challenges. In this study, the cortisol levels in response to an alcohol challenge were compared in sons of alcoholics and in matched controls. Results showed that the sons of alcoholics had a lower response to alcohol. In another part of COGA, Schuckit and Smith (1996) in an 8-year longitudinal study compared the rates of alcohol dependence and alcohol abuse in sons of alcoholics with those rates in a control group. None of the subjects had an alcohol disorder at the onset of the study. Results showed 8 years later that the sons of alcoholics had double the rates of both dependence and abuse as did the control group. Furthermore, having a low level of reaction to alcohol challenges at the beginning of the study was associated with actually developing alcoholism 8 years later. Ongoing portions of COGA hope to use some of these findings to direct molecular genetic studies. Another biological factor that has been associ-
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ated with alcoholism in repeated studies is the decreased activity of the enzyme monoamine oxidase (MAO), particularly the type MAOB (Devor, 1994). The results of a study by Devor, Abell, Hoffman, Tabakoff, and Clonninger (1994) show that decreased platelet MAOB activity is a marker for increased risk of alcoholism and that families in which alcoholism follows a particular course have a higher loading for this genetic risk. In these families, the alcoholism has an earlier onset, does not respond as well to treatment, has a higher comorbidity for disorders such as antisocial personality disorder, and is more prevalent in males. However, the impact of decreased MAOB activity on alcoholic behavior is not known or is its relevance to treatment known. Research on MAOB shows another area where future results may open doors for treatment options. IMPLICATIONS FOR THE PSYCHIATRIC/MENTAL HEALTH ADVANCED PRACTICE NURSE
The ultimate goal of the collective results of the preceding studies on genetics and alcoholism should be to lead to methods for the prevention and treatment of alcoholism. In terms of this goal, research is still in its infancy. A time in the future might be envisioned when all the genetic and environmental factors are sorted out so that these risk factors could be targeted for preventative programs. A time might also be envisioned when any given alcoholic could be genotyped so that interventions could be geared toward that person's specific physiological impairments. However, that time is not here. It is important for the nurse practitioner to examine the current findings for their utility in nursing practice. A known fact is that alcoholism is more prevalent in children of alcoholics. PMHAPNs can use this knowledge to treat the whole family, not just the alcoholic. Family members can be referred to groups analogous to Alcoholics Anonymous for the alcoholic, such as AL-ANON for the significant others, Adult Children of Alcoholics (ACOA) for adult children of alcoholics, and Alateen for teenage children of alcoholics. Many family members of alcoholics suffer from the stress of living with an alcoholic and try unsuccessfully to control the alcoholic's drinking. The above support groups use a modification of the twelve steps of Alcoholics Anonymous to teach family members that they are
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powerless over the alcoholic's drinking and that they need not be controlled by it. These support groups can help at-risk individuals learn how to cope with their own lives, and provide social support, which is a health-promoting factor, and thus reduce environmental risk factors. It is also important for the PMHAPN to use the knowledge that having a frst-degree relative with alcoholism is a predictor of increased risk for alcoholism. People at risk should be educated to the idea that they may be at greater risk for the development of alcoholism so that they can modify their environments to possibly reduce this risk. They need to know that increased risk does not mean that they are going to be an alcoholic; it does mean that the person may have a predisposition to this behavior if the person develops an alcoholic lifestyle. A person at risk can learn not to choose friends who drink excessively and to avoid using alcohol to numb unacceptable feelings or as a reward. A susceptible person can learn to accept responsibility for life choices. Family history of alcoholism should be part of the family history section of the nursing assessment in any patient along with the person's own alcohol use. A positive family history might alert the nurse to be more sensitive to assessing for alcohol abuse and genetically related disorders such as carbohydrate-craving obesity, gambling, and other substance abuse. Knowledge that the A1 allele of the DRD2 gene is associated with this particular spectrum of disorders provides the rationale for broadening the assessment beyond drinking behaviors. Early detection through a thorough nursing assessment can result in an earlier treatment and perhaps a better prognosis than delayed treatment would. This same research on the DRD2 gene might be useful in supportive therapy. If people with this gene have less of these dopamine receptors and, therefore, less ability to stimulate their pleasure centers, perhaps they could be taught other ways to release natural endorphins, such as physical activity. Perhaps a regular aerobic routine would prove beneficial, and its efficacy could be tested through clinical research. Results from the rodent studies related to the differing processing mechanisms of endorphin peptides have led to the treatment of alcohol recovery with an opiate antagonist Naltrexone (DupontPharma Co., Wilmington, DE). It is hypothesized that alcoholics metabolize alcohol differently so
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that more powerful opiate-like substances called endorphin peptides are formed and serve as powerful reinforcers of alcohol. Naltrexone blocks the effects of the endorphin and seems to reduce cravings in recovering alcoholics. According to a commentary by Gordis (1996), the combination of Naltrexone and counseling extended the time to the first drink and reduced the number of binge-type relapses in recovering alcoholics. This same information about the differing endorphin-processing mechanisms in alcoholics could be useful in the education of alcoholics. Often people with alcohol abuse problems have difficulty accepting the idea that they must be abstinent and think they can teach themselves to drink in moderation. The research pointing to a more powerful reinforcing opiate-like substance in the alcoholic who drinks could provide useful knowledge to help explain to the alcoholic why drinking in moderation is more than an issue of willpower. The PMHAPN can explain to patients with alcoholism how drinking in moderation to them may be similar to using heroin in moderation. Most people understand that heroin is a powerfully addictive drug, and this analogy might, therefore, prove a useful one for the alcoholic. An interesting observation about the protective nature of one specific allele of the ALDH2 gene is that this gene functions in the same manner as the drug disulfiram (Antabuse [Wyeth-Ayerst Laboratories, Philadelphia, PAl) that is sometimes used to help alcoholics maintain sobriety. Disulfiram inhibits ALDH thus blocking the metabolism of acetaldehyde, a product of alcohol metabolism (Townsend, 1995). The accumulation of acetaldehyde leads to uncomfortable reactions in the person on disulfiram who ingests alcohol just as it does in the person with the specific allele of the ALDH2 gene. One difference is that in the person on disulfiram, the reactions can be life threatening because of the very high accumulation of acetaldehyde. Perhaps, as part of the education of the patient prescribed disulfiram, the nurse can explain that a few people have a protective mechanism similar to that provided by the drug disulfiram. This explanation might help the person see this treatment as logical. The nurse can also use the growing body of knowledge on the genetic basis of alcoholism in both supportive therapy and community education targeted toward the nature of alcohol use disorders. These disorders have both a genetic and an environ-
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mental basis. The genetic basis supports the disease model of alcoholism that is in opposition to the model that purports it to be a moral problem or one of a character weakness. In supportive therapy the nurse can use the disease model to reinforce that alcoholism is a treatable disease and not a curable disease as are many chronic illnesses thought to also be complex genetic disorders such as hypertension and diabetes. Lifestyle changes can impact the progression of alcoholism just as they can impact the progression of hypertension and diabetes. This kind of knowledge can help the alcoholic better understand the disease and why lifelong compliance to treatment is advisable. Because alcoholism is a genetic disorder, the nurse might think of the possibility of genetic counseling. Other than educating children of alcoholics that they may be at a greater risk for developing alcoholism, there is no current advisable role for genetic counseling in relation to alcoholism. A significant principle of genetic counseling is that it is provided only on request, and the biggest constraint to genetic counseling related to alcoholism is the inability to provide even the most basic information such as the individual's specific risk (Hall, 1996). For diseases in which genetic counseling is appropriate, it is possible to do a test and provide an individualized assessment of recurrence risk. This is not possible for alcoholism. Another problem is that there is a combination of genetic and environmental factors in alcoholism, and it may be more important for an individual to know the environmental risks that can be manipulated than to know the genetic risks. Still another problem is that alcoholism is a disease with a late onset. Even if the recurrence risk at some future time could be predicted, what benefit would this knowledge provide? Unless there were a preventable treatment, the information to the person would not be very useful and might be harmful in terms of being a social stigma and possibly increasing insurance liability. The ethical implications would be enormous. The Committee on Assessing Genetic Risks (Andrews, Fullarton, Holtzman, & Motulsky, 1994, p. 106) " . . . recommends that, if predictive tests for mental disorders become a reality, results must be handled with stringent attention to protect an already vulnerable population." The committee also recommended expanding the graduate curriculum of nurses to include genetic counseling because health care practitioners, including nurses,
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are not sufficiently educated to provide this service, which might be frequently requested as genetic knowledge explodes and more specific tests become available. In summary, research supports that alcoholism is a complex genetic disorder with both multiple genetic and environmental influences. The literature reports much controversy over the appropriate designs and analytical tools with which to study the genetic influences of alcoholism. Research suggests that genetic markers may be associated with the varying types of the disorder and the severity of the disorders. Some of the markers that have repeated studies implicating them are the A1 allele of the DRD2 gene and a specific allele of the ALDH2 gene. In rodent studies there are differences in endorphin peptide processing in response to alcohol in some rodent strains. The P M H A P N can use the results of genetic research to assess and educate patients about the disease and the rationale for selected treatments, to refer at-risk individuals to support groups, and for supportive therapy. Genetic counseling based on any specificity of individual risk is not currently available, and nurses who may eventually become involved in this area should become educated to interpret future tests, provide genetic counseling, and be cognizant of the multiple inherent ethical implications.
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