Research Highlights

Research News
Sunday, September 20, 2015

 In a commentary published in April in the journal Alcoholism: Clinical and Experimental Research, Raye Litten, Ph.D., and other NIAAA scientists describe the evolution of our understanding of the heterogeneity of alcohol use disorder (AUD), and outline new treatment and research regimes that follow from the recognition that alcohol problems are manifested along a continuum of severity, ranging from the occasional binge drinker to the chronic relapsing heavy drinker.

“Each patient develops an AUD based on his or her unique neurobiological makeup and lifetime experiences—a complex interaction of underlying genetic and environmental mechanisms,” write Dr. Litten and his colleagues. “This heterogeneity can be understood as a number of subphenotypes, each having its own unique profile of drinking pattern, motivation for drinking, alcohol-related consequences, and neurobiological underpinnings.”

“Not surprisingly,” they note, “a wide variety of clinically acceptable treatment outcomes are possible with AUD, including not only abstinence, but also low-risk drinking, and even some less-conservative forms of moderate drinking.”

A menu of effective treatment options is available today, including three FDA-approved medications to treat alcohol dependence—disulfiram, oral and injectable naltrexone, and acamprosate. A variety of behavioral therapies have also been shown to be effective. However, the authors note that due to the complex heterogeneity of AUD, no single treatment will work for every person with AUD. However, ongoing research progress in both the neurobiology and pharmacogenetics of AUD holds the promise of identifying biologically based AUD subtypes and the selection of treatments to target those subtypes.

“Neurobiological researchers have identified more than 30 molecular targets that appear to alter people’s craving or drinking behaviors,” they write, “and emerging knowledge of the neurobiology and neurocircuitry of AUD provides a framework for organizing targets.”

Dr. Litten and his colleagues say that current evidence allows alcohol addiction, in general, to be broken down into a three-stage cycle: binge–intoxication, withdrawal–negative affect, and preoccupation–anticipation.

“These three stages interact with and build on one another, becoming more intense, and ultimately leading to the pathological state known as addiction. Within this concept, AUD can be conceptualized as a disorder that involves elements of both impulsivity and compulsivity. As an individual moves from impulsivity to compulsivity, a shift occurs from positive rein-forcement to negative reinforcement driving the motivated behavior.”

To promote systematic research discovery efforts based on current knowledge, the NIAAA scientists propose a new framework, called Alcohol Addiction Research Domain Criteria, modeled after a program in use at the National Institute of Mental Health (NIMH). Such a system, they say, enables researchers to “drill down” to the core mechanisms underlying dysfunction, and link behavior and mood to their brain function, neural circuitry, neurotransmitters, and genes.

“The development of an alcohol addiction domain criteria-based framework to conceptualize research on AUD that probes the sources of the disorder could serve to organize and advance our understanding of alcohol addiction,” the authors conclude. “Identifying the major domains underlying AUD and how the profile of vulnerability to each domain varies among individuals, and over time, not only will be vital to understand the heterogeneity of the disorder, but will also enable us to tailor treatment effectively to the individual. This will substantially advance the field of personalized medicine, and foster the translation of findings from basic research into practical, clinical applications.”


Litten, R.Z.; Ryan, M.L.; Falk, D.E.; Reilly, M.; Fertig, J.B.; and Koob, G.F. Heterogeneity of alcohol use disorder: Understanding mechanisms to advance personalized treatment. Alcoholism: Clinical and Experimental Research 39(4):579–584, 2015. PMID: 25833016



Reprinted from the NIAAA Spectrum, Volume 7, Issue 3, September 2015.

Research News
Wednesday, February 17, 2016

Two to three brief training sessions can significantly increase pediatricians’ use of screening and brief interventions to help their patients with substance use and mental health problems, according to a large, 2-year trial supported by NIAAA. The study also found that pediatric practices can increase delivery of these services by adding behavioral health clinicians to their teams.

Mounting evidence supports the use of screening, brief intervention, and referral to treatment (SBIRT) in pediatric practices to reduce underage drinking and its harmful consequences. Pediatricians often report barriers to conducting SBIRT, however, including time constraints and a lack of training.

Researchers at Kaiser Permanente Northern California compared two practical ways to overcome these barriers and increase the delivery of SBIRT services in a trial involving about 50 pediatricians and 1,900 adolescents. One group of pediatricians was offered three 60-minute SBIRT training sessions then encouraged to conduct assessments and brief interventions when needed. A second group had one 60-minute training session, then was encouraged to assess and refer patients as needed for interventions by clinical psychologists “embedded” in their practices. For comparison, a third, “usual care” group had access to the same clinical guidelines and tools but no SBIRT training or psychologists in their practices.

The researchers found that, following SBIRT training, the pediatrician-only group was about 10 times more likely to conduct brief interventions with patients deemed at risk, compared with usual care pediatricians (16 percent for the trained group vs. 1.5 percent for usual care). In the pediatrician-plus-psychologist group, 24 percent of at-risk patients received brief interventions.

Although overall pediatrician attention to behavioral health concerns was still low following training, the researchers indicated that embedding behavioral health clinicians in primary care could be a cost-effective way to increase SBIRT delivery. Future analyses will examine patient outcomes and the cost-effectiveness of the two SBIRT delivery options.


Sterling, S.; Kline-Simon, A.H.; Satre, D.D.; Jones, A.; Mertens, J.; Wong, A.; and Weisner, C. Implementation of screening, brief intervention, and referral to treatment for adolescents in pediatric primary care: A cluster randomized trial. JAMA Pediatrics 169(11):e153145, 2015. PMID: 26523821


Reprinted from the NIAAA Spectrum, Volume 8, Issue 1, February 2016.

Research News
Saturday, February 20, 2016

Adults drank more alcohol in 2012–2013 than they did in 2001–2002, according to the most recent National Epidemiologic Survey on Alcohol and Related Conditions (NESARC). NESARC–III is a cross-sectional survey sponsored, designed, and directed by NIAAA and is the largest study ever conducted on the co-occurrence of alcohol use, drug use, and related psychiatric conditions.

To assess how drinking patterns have changed over time, researchers compared the NESARC–III data with that from Wave 1 NESARC. In both surveys, which had similar objectives and content areas, researchers assessed a large sample of U.S. adults through personal interviews conducted in participants’ homes. However, unlike Wave 1 NESARC, NESARC–III researchers collected saliva samples from participants for future DNA analyses.

Data analysis revealed that between 2001–2002 and 2012–2013, past-year drinking prevalence increased from 65.4 percent to 72.7 percent, and the prevalence of monthly binge drinking increased from 21.5 percent to 25.8 percent. Likewise, overall frequency of drinking increased from 83.5 days per year to 87.9 days per year. The authors of the study observed that these statistics, along with the increase in daily alcohol consumption (from 0.628 ounces to 0.751 ounces), indicate “a wetter drinking climate.”

One particularly striking finding was that African Americans experienced disproportionate increases in past-year drinking prevalence (from 53.2 percent to 66.1 percent) and past-month binge drinking prevalence (from 19 percent to 27.7 percent), as well as average daily volume (from 0.751 ounces to 1.033 ounces), compared with Caucasians. The authors suggest this may indicate disparities in treatment availability and/or treatment seeking.

Another notable finding was that percent increases in prevalence and overall drinking frequency were about twice as high for women as for men, prior to adjustment for sociodemographic differences. Adjusting for these differences, women demonstrated larger increases than men in all consumption measures. According to the authors, this finding may contribute to evidence of a closing gender gap in heavy drinking.

Looking ahead, scientists will continue to analyze the various waves of NESARC data to advance our understanding of drinking trends through comparison of survey results over time.

Dawson, D.A.; Goldstein, R.B.; Saha, T.D.; and Grant, B.F. Changes in alcohol consumption: United States, 2001-2002 to 2012-2013. Drug and Alcohol Dependence 148:56–61, 2015. PMID: 25620731


Reprinted from the NIAAA Spectrum, Volume 8, Issue 1, June 2016.

Research News
Friday, February 19, 2016

In a recent study, Cindy L. Ehlers, Ph.D., and colleagues examined the clinical course of alcohol use disorder (AUD)—as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM–5)—in a sample of young adult (ages 18–30) individuals of Mexican American (MA) and Native American (NA) descent.

Face-to-face interviews using the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA) were conducted with 619 MA and 510 NA community-based participants recruited in southwest California. Of the total sample of 1,129 participants, 634 (56 percent) met criteria for a lifetime diagnosis of DSM–5 AUD. Mild AUD was found in 22 percent of participants, moderate AUD in 14 percent, and severe AUD in 20 percent. Further data analysis revealed that 70 percent of the NA men, 64 percent of the NA women, 56 percent of the MA men, and 42 percent of the MA women met the lifetime diagnostic criteria for AUD.

The researchers examined the clinical course of AUD, as defined by order and progression of 36 alcohol-related life events, within their MA and NA young adult sample. A comparison of these alcohol-related life experiences and their order of occurrence over time was made between male and female and between MA and NA participants. NAs reported more alcohol-related life events and at an earlier age than MAs. Otherwise, a high degree of similarity in clinical course was found between men and women and between MA and NA individuals. The researchers also analyzed their data across severity of DSM–5 AUD disorder (mild, moderate, or severe). The high degree of similarity in the clinical course for moderate and severe AUD and across genders was not found for mild AUD. This information suggests that mild AUD may not be part of the same clinical continuum as moderate and severe AUD for NA and MA populations.

It should be noted that this study was limited by the specificity of the participant sample, which means the results may not be generalizable to the population as a whole. However, the findings are significant because they are informative for understanding health disparities in the groups studied and because they provide some early insights into the new DSM–5 mild, moderate, and severe AUD categories.


Ehlers, C.L.; Stouffer, G.M.; Corey, L.; and Gilder, D.A. The clinical course of DSM-5 alcohol use disorders in young adult native and Mexican Americans. American Journal of Addiction 24(8):713–721, 2015. PMID: 26346282


Reprinted from the NIAAA Spectrum, Volume 8, Issue 1, February 2016.

Research News
Wednesday, June 22, 2016
Interventions to reduce anxiety and depression may help prevent relapse in individuals with chronic pain who are recovering from alcohol use disorder (AUD). This conclusion comes from a recent study in which investigators reanalyzed data collected from people with chronic pain who participated in one of two major clinical trials on alcohol treatment, one in the United States and one in the United Kingdom. Both trials included the collection of data that allowed the authors of the present study to look at the links between pain, negative affect, and relapse. In the present study, the researchers conducted a separate reanalysis for each of the two original studies.
People in recovery from AUD commonly have relapses to heavy drinking following a stretch of abstinence or cutting back. Previous research has shown that risk factors for relapse include stress, craving, and the “negative affect” states of anxiety and depression. Pain has not been widely studied as a risk factor, even though chronic pain is common and often self-managed with alcohol.
Based on their new analyses, the authors report that people with higher pain levels in both studies tended to have higher levels of negative affect and increased rates of relapse. The key finding, however, was that the participants’ levels of anxiety or depression in both studies predicted relapse better than their particular pain levels.
It is important to note that in the U.K. clinical trial, a high-intensity behavioral intervention called social behavior network therapy (SBNT) appeared to reduce the effects of pain on negative affect and relapse. Participants in that trial were randomly assigned to receive either SBNT, which helped build social networks that supported abstinence or reduced drinking, or a lower-intensity motivational enhancement therapy (MET). In the MET group, participants with greater pain scores at the end of treatment tended to have more heavy-drinking days 12 months later. In contrast, those in the SBNT group with greater pain scores at the end of treatment did not drink significantly more a year later, than those with lower pain scores. The authors suggest that the healthy social support system built by the SBNT group may have reduced the participants’ tendencies to drink heavily in response to pain or negative affect.
The analysis was designed to show associations among pain, negative affect, and alcohol use, but not whether one factor came before or caused another. The authors concluded that the findings lend support for the SBNT intervention as well as future research into the potential benefits of negative- affect treatments for people with AUD and chronic pain.
Witkiewitz, K.; McCallion, E.; Vowles, K.E.; Kirouac, M.; Frohe, T.; Maisto, S.A.; Hodgson, R.; Heather, N. Association between physical pain and alcohol treatment outcomes: The mediating role of negative affect. Journal of Consulting and Clinical Psychology 83(6)1044–1057, 2015. PMID: 2609837
Reprinted from the NIAAA Spectrum, Volume 8, Issue 2, June 2016.