The Science of Alcoholism
Around 75,000 people in the United States die every year as a result of diabetes,1 while about 85,000 deaths per year are directly related to alcohol use.2 Researchers estimated that the annual cost burden of alcohol use in the United States in 2006 was approximately $223 billion.2 Ten percent of deaths in working age adults occur as a result of excessive drinking.3
Despite these rather sobering statistics, binge drinking is a relative social norm in American colleges and beyond. It is difficult to predict which individuals will be able to leave their binge drinking behaviors behind them after college and which individuals will develop longstanding difficulties with alcohol use.
Psychiatrists use the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) to document various mental disorders. In the current edition of the DSM, the diagnoses “alcohol abuse disorder” and “alcohol dependence disorder” were subsumed under the diagnosis of “alcohol use disorder.”4 In this vein, we will subsume the varied, and oftentimes confusing, terms that have been used to describe various forms of alcohol abuse under the broader term “unhealthy alcohol use.”
The average American adult consumed 2.32 gallons of alcohol in 2014.5 Two-and-a-half milk jugs worth of alcohol spaced over a year may not seem like a lot, but keep in mind that this number represents the amount of pure ethanol consumed. Scientists consider a standard drink 12 ounces of beer, 5 ounces of wine, or 1.5 ounces of 80-proof liquor. When one converts the milk jugs full of pure ethanol into standard drinks one finds that the average American consumed almost 500 standard drinks in 2014; or around 9.5 drinks per week. Let’s keep this number in the back of our minds as we proceed.
How do doctors measure unhealthy alcohol use?
There are many different definitions of troubled drinking, but for the purposes of our discussion we will briefly examine “risky use” and “binge drinking.” Risky use has been defined as the amount of alcohol that poses a risk to an individual’s health. Men less than 65 years old are categorized as exhibiting risky use if they consume more than 14 drinks per week or more than 4 drinks on a given day.6 In women less than 65 years old the cutoff for risky use is more than 7 drinks per week or more than 3 drinks in a given day.6
More than one-quarter of American adults meet criteria for risky use.6 Individuals between the ages of 18 and 29 are more than 150% more likely to exhibit unhealthy alcohol use than those aged 30 to 44.7 Men are more than 200% more likely than females to experience unhealthy alcohol use.7
Binge drinking is defined as consuming an amount of alcohol in 2 hours such that your blood alcohol content (BAC) reaches 0.08% (the legal limit for driving). On average, consumption of 4 standard drinks in women and 5 in men over a 2 hour period will achieve this BAC.6
If we now recall that the average American consumes 9.5 standard drinks per week, then the scope of the alcohol problem begins to come into focus. The per capita consumption data does not allow for gender-specific estimates and is likely influenced by outliers, but the close proximity of average consumption and risky use values are concerning. In fact, data from a 2015 study suggests that almost 14% of adults in the United States meet criteria for alcohol use disorder in a given year.8
Is this problem unique to the United States?
In short, no. Historical data from 2004 reveals that almost 11% of adults in Eastern Europe, more than 5% of adults in Western European, and almost 4% of global adults suffered from an alcohol-use disorder in the studied twelve month period.9
Why can some individuals use alcohol responsibly while others exhibit unhealthy alcohol use?
Commensurate with the complexity of the human mind there are numerous contributing factors that lead to the development of unhealthy alcohol use. We will examine two theories that have gained support in the literature known as pharmacologic vulnerability and positive and negative affect regulation theory respectively. First, let’s examine the genetics of pharmacologic vulnerability.
Pharmacologic vulnerability refers to an individual’s unique reaction to alcohol as dictated by their genetic make up and the neurobiology that this encodes. Genes exhibit a strong influence on one’s susceptibility to unhealthy alcohol use, accounting for approximately 50% of an individual’s risk.10 To put this in perspective, the approximate genetic heritability is 50% for body mass index,11 40% for male pattern baldness,12 and 25% for longevity.13
In order to understand how our genes can make us vulnerable to unhealthy alcohol use we must first examine how alcohol creates its euphoric effects in the brain. There are five primary neurotransmitter systems that alcohol effects and we will examine each in turn.
Glutamate is a neurotransmitter central to learning and memory. Alcohol impairs the function of the glutamate system, explaining the memory loss associated with the black or brown outs experienced by those who abuse alcohol.14
Gamma-aminobutyric acid (GABA) functions as the key inhibitory neurotransmitter in the brain and is the target of the anxiety-reducing medications known as benzodiazepines (brand names include Valium and Xanax). Alcohol appears to enhance the effects of GABA in the brain.14
Dopamine is the body’s central neurotransmitter associated with reward and reinforcement. Alcohol increases the release of dopamine.14
The opioid system helps to reduce pain and to modulate mood. Alcohol enhances the release of the body’s own opioids.14
Serotonin helps to regulate mood as well as other core functions of daily living. Alcohol increases the release of serotonin.14
As we can see, alcohol has a wide range of effects that can be summed up as a decrease in glutamate activity and an increase in GABA, dopamine, opioid, and serotonin activity.
The body maintains homeostasis by using a series of enzymes manufactured primarily in the liver to metabolize alcohol. Alcohol is converted first into acetaldehyde by the enzyme alcohol dehydrogenase (ADH). Acetaldehyde is toxic to the body and is hypothesized to produce many of the “hangover” effects synonymous with excessive alcohol use. Acetaldehyde is then converted to acetic acid (the main component of vinegar) by acetaldehyde dehydrogenase (ALDH). Acetic acid can then be used by the body for general metabolic processes.
Interestingly, some people of East Asian heritage experience what is known as the alcohol flush reaction. Alcohol use, even in small amounts, will often lead to a reddening of the face as well as a sensitivity to the nausea and headache-inducing effects of the hangover syndrome. The alcohol flush reaction is driven by a gene variant of ADH that demonstrates increased activity and thus an increased rate of conversion of alcohol to the toxic metabolite acetaldehyde.15
Unfortunately, ALDH is often normal or sometimes even reduced (another gene variant) in this same population and acetaldehyde builds up at the metabolic choke point before the conversion to acetic acid. Interestingly, the drug Antabuse sometimes used to treat unhealthy alcohol use inhibits ALDH, increasing acetaldehyde and generating an aversive nausea and headache for the user who drinks.16
Returning to genetics, how do the five neurotransmitter systems help explain the 50% of unhealthy alcohol use risk that is attributed to one’s genes?
Given what we now know about ADH and the alcohol flush reaction, it may not be surprisingly to learn that individuals who experience the alcohol flush reaction have significantly lower rates of alcoholism as compared with those individuals who can tolerate higher quantities of alcohol. Thus, the genetics that encode the ADH protein influence the development of unhealthy alcohol use by either making the hangover effects better or worse depending on their level of functioning.15
Variant genes in serotonin and GABA regulation decrease an individual’s response to alcohol and increase one’s risk of developing unhealthy alcohol use. In other words, if the body requires and tolerates more alcohol to attain a given effect, it is more likely that the individual will go on to develop unhealthy alcohol use.15
So if you have normal ADH and the serotonin and GABA gene variants that decrease your response to alcohol does that guarantee that you will develop unhealthy alcohol use?
Genetics do play a fairly large role in conferring susceptibility to unhealthy alcohol use, but the fact that the risk is only partially explained by genetics tells use that the environment plays an important role as well. Gene-environment interactions are revealing themselves to be key etiological dyads in understanding human disease. Rather than a metaphorical on/off light switch of disease, genes appear to function as a dimmer switch that augments the effects of the environment on the disease process.
Another example of genetic susceptibility to unhealthy alcohol use is monoamine oxidase A (MAOA) enzyme variants. MAOA metabolizes norepinephrine, dopamine, and serotonin, reducing their availability in the brain. Thus, lower levels of MAOA correlate with higher available levels of norepinephrine, dopamine, and serotonin. As it turns out, higher levels of norepinephrine, dopamine, and serotonin predict an increased stress response and an increased risk of psychiatric disease, including unhealthy alcohol use.15
The proposed theory explaining this susceptibility cites the effects of high levels of norepinephrine, dopamine, and serotonin in the hippocampus of those individuals affected by low MAOA activity. The hippocampus is involved in the formulation and retrieval of memories. Studies have shown that increased levels of neurotransmitters increase the recording and subsequent retrieval of negative events.15
Another gene-environment dyad exists in the genes for the serotonin transporter (SERT). Certain genetic variants of the SERT gene confer a susceptibility to psychiatric disease including unhealthy alcohol use by increasing an individual’s vulnerability to stressful environmental conditions.15
Now that we have thoroughly examined the pharmacologic vulnerability to unhealthy alcohol use, let’s turn to positive and negative affect regulation.
Positive and negative affect regulation can be thought of as an individual’s ability to attain happiness while managing discontent. We have previously discussed personality and the five factor model recalled by the OCEAN mnemonic (openness to experience, conscientiousness, extraversion, agreeableness, and neuroticism). Positive affect regulation roughly correlates with extraversion while negative affect regulation roughly correlates with conscientiousness and neuroticism.
As a refresher, one component of the extraversion domain in personality is the degree of positive affect. Also recall that conscientiousness indicates our ability to keep impulsivity in check while the neuroticism domain directly describes the degree of negative emotionality and susceptibility to stress.
As we discussed in the personality article, the heritability of personality is roughly 50%. Affect regulation is much more complex than a simple personality correlate, but the correlation can serve as a shortcut to understanding why a negative mood may affect one individual differently than another. The stress of socializing with strangers may lead an individual with low innate positive affect and high innate negative affect to augment their mood with alcohol, employing its euphoric and anxiolytic effects to mitigate stress.
We have covered a lot of ground in our attempt to explain vulnerabilities to unhealthy alcohol use so let’s try to sum up by describing the so-called perfect storm scenario of unhealthy alcohol use susceptibility.
Let’s imagine an individual with average ADH and ALDH function who metabolizes alcohol more or less normally. This same susceptible individual possesses gene variants of GABA and serotonin systems that decrease his or her response to alcohol, leading to an increased tolerance of its effects. Unfortunately, this individual also has decreased MAOA activity and dysfunctional SERT activity both of which lead to an increased negative psychological reaction to life stress. Further complicating this hypothetical individual’s prognosis is his or her relative deficit of innate happiness and overabundance of innate discontent. The summative effect of these factors would leave the hypothetical individual extremely vulnerable to the development of unhealthy alcohol use in the right environmental context.
The reader should note that the aforementioned perfect storm of vulnerability, minus variants in ADH and ALDH, has also been associated with various mental illnesses.
Okay, so we have examined the development of unhealthy alcohol use in depth, but what about the prognosis?
Unhealthy alcohol use can be treated with psychosocial and pharmacologic methods. Alcoholics anonymous is perhaps the best known psychosocial treatment for unhealthy alcohol use, but there are many other forms of treatment. There are numerous pharmacologic treatments available with variable levels of efficacy. The medication naltrexone has the most evidence at the moment and has been shown to reduce the risk of heavy drinking by about 15%.17 Naltrexone works by blocking opioid receptors and the resultant reinforcing euphoric effects associated with alcohol-stimulated receptor activation.18
Longitudinal studies of unhealthy alcohol use have demonstrated the intuitive positive correlation between the length of sobriety and risk of relapse. One study revealed that those with less than 1 year of sobriety had an almost 75% chance of relapse while those with greater than 5 years of sobriety had less than a 15% risk of relapse.19 Thus, after 5 years of sobriety your risk of relapse is reduced by 80%.
Another study revealed a similar trend, demonstrating that after 5 years of sobriety the risk of relapse is around 10% while after 15 years of sobriety the risk of relapse was less than 1%.20
So it seems that 5 years is a major milestone in an individual’s sobriety.19-22 One should note that the approximate 10-15% risk of relapse after 5 years of sobriety for an individual with a history of unhealthy alcohol use is similar to the 14% prevalence of unhealthy alcohol use in the US general population.8,19,20
Thus, after 5 years, the recovering alcoholic has successfully lowered his or her risk of redeveloping unhealthy alcohol use to that of an individual randomly sampled from the general population. Read a complete outline of the statistics here.
This is a striking observation and exemplifies the potential for recovery contained within even the darkest recesses of the unhealthy alcohol use disease. In spite of significant genetic loading, the human mind possesses enormous powers of will and intention that offers hope even in the bleakest of conditions.
- Health, United States, 2014: With special feature on adults aged 55–64. CDC.gov. http://www.cdc.gov/nchs/data/hus/hus14.pdf. Accessed June 18, 2016.
- Bouchery EE, Harwood HJ, Sacks JJ, Simon CJ, Brewer RD. Economic costs of excessive alcohol consumption in the U.S., 2006. Am J Prev Med. 2011;41(5):516-524. doi:10.1016/j.amepre.2011.06.045.
- Stahre, M. Contribution of excessive alcohol consumption to deaths and years of potential life lost in the United States. Preventing chronic disease. 2014;11.
- American Psychiatric Association. Diagnostic and statistical manual of mental disorders (DSM-5®). American Psychiatric Pub. 2013.
- Haughwout, S. P., LaVallee, R. A., & Castle, M. I. J. P. Surveillance Report #104 Apparent Per Capita Alcohol Consumption: National, State, and Regional Trends, 1977-2014. NIH.gov. 2015.
- US Department of Health and Human Services, & US Department of Health and Human Services. Helping patients who drink too much: a clinician’s guide. National Institutes of Health. National Institute on Alcohol Abuse and Alcoholism. NIH Publication. 2005;(07-3769).
- Hasin, D. S., Stinson, F. S., Ogburn, E., & Grant, B. F. Prevalence, correlates, disability, and comorbidity of DSM-IV alcohol abuse and dependence in the United States: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Archives of general psychiatry. 2007;64(7), 830-842.
- Grant, B. F., Goldstein, R. B., Saha, T. D., Chou, S. P., Jung, J., Zhang, H., … & Hasin, D. S. Epidemiology of DSM-5 alcohol use disorder: results from the National Epidemiologic Survey on Alcohol and Related Conditions III. JAMA psychiatry. 2015;72(8), 757-766.
- Rehm, J., Mathers, C., Popova, S., Thavorncharoensap, M., Teerawattananon, Y., & Patra, J. Global burden of disease and injury and economic cost attributable to alcohol use and alcohol-use disorders. The Lancet. 2009;373(9682), 2223-2233.
- Prescott, C. A., & Kendler, K. S. Genetic and environmental contributions to alcohol abuse and dependence in a population-based sample of male twins. American Journal of Psychiatry. 1999.
- Silventoinen, K., Magnusson, P. K., Tynelius, P., Kaprio, J., & Rasmussen, F. Heritability of body size and muscle strength in young adulthood: a study of one million Swedish men. Genetic epidemiology. 2008;32(4), 341-349.
- Adhikari, K., Fontanil, T., Cal, S., Mendoza-Revilla, J., Fuentes-Guajardo, M., Chacón-Duque, J. C., … & Jaramillo, C. A genome-wide association scan in admixed Latin Americans identifies loci influencing facial and scalp hair features. Nature communications. 2016;7.
- Herskind, A. M., McGue, M., Holm, N. V., Sörensen, T. I., Harvald, B., & Vaupel, J. W. The heritability of human longevity: a population-based study of 2872 Danish twin pairs born 1870–1900. Human genetics. 1996;97(3), 319-323.
- Chastain, G. Alcohol, neurotransmitter systems, and behavior. The Journal of general psychology. 2006;133(4), 329-335.
- Ducci, F., & Goldman, D. Genetic approaches to addiction: genes and alcohol. Addiction. 2008;103(9), 1414-1428.
- Thomasson, H. R., Crabb, D. W., Edenberg, H. J., & Li, T. K. Alcohol and aldehyde dehydrogenase polymorphisms and alcoholism. Behavior genetics. 1993;23(2), 131-136.
- Rösner, S., Hackl-Herrwerth, A., Leucht, S., Vecchi, S., Srisurapanont, M., & Soyka, M. Opioid antagonists for alcohol dependence. Cochrane Database Syst Rev. 2010;12.
- Maisel, N. C., Blodgett, J. C., Wilbourne, P. L., Humphreys, K., & Finney, J. W. Meta‐analysis of naltrexone and acamprosate for treating alcohol use disorders: when are these medications most helpful?. Addiction. 2013;108(2), 275-293.
- Dennis, M. L., Foss, M. A., & Scott, C. K. An eight-year perspective on the relationship between the duration of abstinence and other aspects of recovery. Evaluation Review. 2007;31(6), 585-612.
- Vaillant, G. E. A 60‐year follow‐up of alcoholic men. Addiction. 2003;98(8), 1043-1051.
- Vaillant, G. E. A long-term follow-up of male alcohol abuse. Archives of General Psychiatry. 1996;53(3), 243-249.
- Dawson, D. A., Goldstein, R. B., & Grant, B. F. Rates and Correlates of Relapse Among Individuals in Remission From DSM‐IV Alcohol Dependence: A 3‐Year Follow‐Up. Alcoholism: Clinical and Experimental Research. 2007;31(12), 2036-2045.