Goal 2: Diagnostics & Epidemiology
Improve Diagnosis and Tracking of Alcohol Misuse, Alcohol Use Disorder, and Alcohol-Related Consequences
Alcohol misuse remains a formidable public health problem. It is the fourth-leading preventable cause of death in the United States and the fifth-leading risk factor for death and disability worldwide.25 In addition to its adverse effects on individual health and well-being, alcohol misuse takes an enormous toll on families, communities, and society. Efforts to prevent and treat alcohol-related problems must be designed for each of these domains.
Changing patterns of alcohol consumption, shifts in the burden of alcohol-related disease, and shifts in the demographic composition of the United States pose new challenges for alcohol prevention and treatment. A recent study found an increase in mortality among white, middle-aged Americans primarily due to drug and alcohol overdoses, suicide, and cirrhosis and other chronic liver diseases. Although men are still more likely than women to drink alcohol and to drink more when they do, the magnitude of these differences is diminishing as binge and extreme binge alcohol use by women increases. This is particularly alarming, because women who drink are at higher risk for certain alcohol-related diseases, including alcoholic liver disease (ALD) and alcohol-related heart and muscle diseases, compared with men who drink. Moreover, drinking during pregnancy introduces a risk that a child will be born with a fetal alcohol spectrum disorder. By 2030, more than half of all Americans are projected to belong to racial or ethnic minority groups, and one in five Americans is projected to be age 65 or older.26 As noted above, some minority groups bear a disproportionate burden of alcohol-related problems, and older adults are at higher risk of unintentional alcohol-related injuries, are more likely to experience health problems exacerbated by drinking, and are more likely to take medications, many of which can have adverse interactions with alcohol. The ongoing military conflicts in Iraq and Afghanistan have also influenced patterns of alcohol-related disease: more than 2.1 million service members have been deployed since 2001,27 and those returning from combat duty face a dramatically increased risk of alcohol use disorder (AUD) and other mental health conditions.
To reduce the burden associated with alcohol misuse in these, and indeed in all, populations, it is essential to define the scope and magnitude of the problems and the factors that contribute to them. Therefore, NIAAA will continue to support research to identify behavioral and biological markers of alcohol use and alcohol-related conditions, develop and optimize methods for assessing these markers, and establish precise estimates of alcohol use, misuse, and related conditions.
To advance these goals, NIAAA will support the following objectives:
Objective 2a: Improve the diagnosis of alcohol use disorder
The fifth and current edition of the American Psychiatric Association’s Diagnostic and Statistical Manual of Mental Disorders (DSM-5) provides clinicians with a basis for diagnosing AUD as mild, moderate, or severe based on how many of 11 equally weighted symptoms a patient experiences.8 These symptoms are largely associated with adverse consequences of substance use, as well as indicators of alcohol tolerance, withdrawal, and escalating or uncontrolled use. When properly assessed, the DSM is a statistically reliable and valid tool for diagnosing substance use disorders (SUDs). Of note, the DSM criteria for AUD were derived from clinical experience and research with adults. Although clinicians do use these criteria to diagnose AUD in adolescents, concerns have been raised about applying them to this population.
Even among adults, the DSM-5 criteria do not reflect the complex and heterogeneous pathophysiology underlying AUD. A patient develops AUD based on a combination of his or her unique biological makeup and life experiences, and there is considerable variation in the way the disorder is expressed among individuals. Developing diagnostic measures that reflect the variation in AUD phenotypes may lead to new and improved treatments and better matching of treatments to patient needs.
NIAAA has proposed developing the Addictions Neuroclinical Assessment as a framework for classifying individual differences in AUD based on the genetic, neurobiological, and behavioral phenotypes corresponding to an individual’s disorder. (See “Addictions Neuroclinical Assessment.”) The Institute will support research to identify these phenotypes, or functional domains, and the biological mechanisms that give rise to them. Preclinical studies employing animal models of addiction will continue to be an important avenue for identifying these functional domains. Together with clinical studies, this work will provide a deeper understanding of the biological underpinnings of AUD. It will also provide a basis for identifying AUD biomarkers and specifying a panel of assessments that can be used to identify clinically relevant AUD subtypes, leading to tailored AUD treatment interventions and better outcomes for more people.
To advance these goals, NIAAA will pursue research and related initiatives to:
- Develop a clinical assessment system using cognitive, behavioral, and biological (e.g., genetic, neuroimaging, and neuropsychological) measures to diagnose and classify individuals of all ages with AUD and other SUDs.
- Evaluate this clinical assessment against other frameworks for diagnosing AUD, tailoring treatment to the individual, and assessing recovery.
Objective 2b: Develop new approaches for diagnosing fetal alcohol spectrum disorders, enabling early interventions
The prevalence of fetal alcohol spectrum disorders (FASD) in the U.S. general population is estimated to be between 20 and 50 per 1,000 live births.28 Establishing more precise estimates of FASD is complex due to challenges assessing prenatal alcohol exposure and FASD. Although various alcohol biomarkers exist, they are not reliable enough to use as assays for prenatal alcohol exposure in everyday clinical practice. Work to identify and validate such markers continues. In addition, NIAAA supports research to improve FASD diagnosis. Many individuals with FASD have cognitive and behavioral problems that are also associated with other developmental disorders. Moreover, whereas people with fetal alcohol syndrome, the most clinically recognizable form of fetal alcohol spectrum disorder, typically have hallmark facial characteristics that facilitate its diagnosis, the facial features associated with other forms of FASD are often very subtle and may even be absent. Recently, NIAAA-funded researchers developed three-dimensional photography and computerized image analysis techniques that can enhance the detection of a broad range of alcohol-induced facial characteristics in children who were prenatally exposed to alcohol. This technology makes it possible to provide more accurate diagnoses of FASD and at an earlier age. It employs three-dimensional cameras routinely used in medical care and photographic images that could be sent for analysis to diagnostic centers anywhere in the world. This technology has the potential to enable widespread FASD screening and early intervention, including for children who do not have access to a clinician with the expertise to diagnose FASD. (See “Three-Dimensional Facial Imaging.”)
To improve the identification of prenatal alcohol exposure, the diagnosis of FASD, and early intervention with individuals affected by FASD, NIAAA will support studies to:
- Develop and evaluate pre- and postnatal assays to detect prenatal alcohol exposure and injury—including assays using metabolic and epigenetic biomarkers, in utero sonography, and neuroimaging—to facilitate early intervention and improve outcomes for individuals affected by prenatal alcohol exposure.
- Improve the sensitivity of three-dimensional photography and computerized image analysis and evaluate the use of this technology for detecting FASD in individuals of varying age, race, and ethnicity in a wider range of settings.
- Refine the understanding of the neurobehavioral phenotypes associated with FASD to improve diagnosis and distinguish individuals with FASD from those with other neurodevelopmental conditions.
- Establish more precise estimates of the prevalence of FASD in the United States to improve health outcomes for individuals with these disorders.
Objective 2c: Develop and evaluate measures to improve the diagnosis of alcohol-related organ damage, especially alcoholic liver disease, and assess its progression
Although the liver breaks down most of the alcohol a person consumes, this process generates dangerous metabolites and byproducts that can damage liver cells, promote inflammation, and weaken the body’s natural defenses. Advances in biomarker research and the development of technologies such as liver elastography, a noninvasive, ultrasound-based method of assessing liver disease, may facilitate earlier detection of alcohol-induced liver injury. Additional research is needed to refine these and other methods for diagnosing ALD and preventing its progression to more serious and potentially fatal conditions. In addition to ALD, chronic alcohol misuse is associated with damage to other organ systems and with other serious medical conditions. Attribution of a causative role for alcohol in many of these conditions is, however, often subject to considerable uncertainty, since the organ damage may occur with or without alcohol misuse. Nonetheless, organ damage is often exacerbated in those individuals with a history of problem drinking.
To improve the diagnosis of alcohol-related diseases and generate appropriate therapeutic strategies for them, NIAAA will support studies to:
- Develop and validate noninvasive methods of assessing organ injury to improve detection, and assess the status, of ALD.
- Identify biomarkers to distinguish alcoholic and nonalcoholic causes for disease and to monitor the progression of alcohol-related diseases and the effectiveness of treatments.
Objective 2d: Track the prevalence, patterns, and trends of alcohol use, misuse, and alcohol use disorder; co-occurring conditions; and alcohol-related consequences across the lifespan
NIAAA has a long history of supporting rigorous epidemiological research to identify and track patterns of alcohol use and misuse, drinking-related outcomes, and individual and environmental variables that confer risk or resilience to these outcomes. NIAAA’s National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) is the largest and most comprehensive national survey conducted on patterns of alcohol use, AUD, and co-occurring mental and physical disabilities. First conducted in 2001, with subsequent surveys administered in 2004 and 2012, data collected through NESARC has had a profound impact on alcohol research and public health. Analyses of NESARC data showed that people who begin to drink at a young age are more likely to develop AUD later in life and at a younger age, experience more and longer episodes of AUD, and meet more diagnostic AUD criteria. Data from the most recent survey demonstrate that extreme binge drinking—drinking beyond the binge threshold—is increasing, and there has been a significant increase in AUD over the past decade.29
In addition to providing data on the distribution and determinants of alcohol-related consequences, epidemiologic research can inform interventions. Studies have demonstrated that alcohol policy interventions can have significant effects on public health outcomes. Every state has established a law against driving with a blood alcohol concentration (BAC) of 0.08 percent or above, and all states have adopted “zero tolerance” laws that mandate lower BAC levels for drivers younger than age 21. These laws, combined with other policies designed to deter driving after drinking, have helped reduce rates of alcohol-related traffic fatalities in the United States by 67 percent since 1982.30 (See “Alcohol- vs. Non–Alcohol-Related Traffic Fatalities in the United States.”) Among the policies with the best evidence of effectiveness is the minimum legal drinking age of 21. Since the early 1980s, 16- to 20-year-olds have experienced the greatest reduction in alcohol-related crashes, and the percent of high school seniors who engage in binge drinking has been cut in half.31 Research on how policy changes affect alcohol use and related outcomes continues to be important, particularly as new policies relevant to substance use are implemented. NIAAA’s Alcohol Policy Information System (APIS), a database that tracks alcohol-related policies at the State and Federal levels, facilitates research on the impact and effectiveness of these policies. APIS was recently expanded to include policies related to the recreational use of marijuana and drugged-driving laws.
To better understand the nature and scope of individual- and population-based differences in alcohol and other substance use, the outcomes associated with substance use, and the complex biopsychosocial factors that contribute to these outcomes, NIAAA will:
- Support epidemiologic research on patterns of alcohol use, alcohol misuse (including extreme binge drinking), and AUD; alcohol-related consequences; and treatment.
- Use epidemiologic data to identify and track populations that are differentially vulnerable to alcohol misuse, AUD, and other alcohol-related consequences.
- Support epidemiologic and systems science research to elucidate how biological and environmental determinants interact to impact alcohol misuse and related consequences.
- Support research to examine how substance use policies, including those relevant to substance use treatment and the changing legal status of marijuana, affect alcohol and other drug use and their consequences.
Addictions Neuroclinical Assessment
NIAAA has proposed developing an Addictions Neuroclinical Assessment (ANA) for assessing and classifying individual differences in key functional domains involved in alcohol use disorder (AUD): incentive salience, negative emotionality, and executive function. The ANA will include a multidimensional battery of tests, including genetic and other “omics” analyses, neuroimaging, and cognitive and behavioral assessments, designed to assess individual variation in each of these domains. The results of these assessments will be used to identify clinically relevant AUD subtypes and guide the provision of individually tailored AUD treatment strategies.
Three-Dimensional Facial Imaging
Researchers funded by NIAAA have developed three‐dimensional photography and computerized image analysis techniques that can enhance the detection of alcohol-induced facial features in children who were prenatally exposed to alcohol. Facial signatures captured through this method can be visualized as heat maps, such as the one shown here, which depicts differences in facial features between an individual with fetal alcohol syndrome (FAS) and age-matched control individuals. Red indicates where facial features are contracted, blue is where they are expanded, and green is where they are similar, in the individual with FAS compared to agematched controls. Image developed by Drs. Peter Hammond and Michael Suttie, Collaborative Initiative on Fetal Alcohol Spectrum Disorders.