2013 Grant Project Profiles
ABMRF/The Foundation for Alcohol Research has played a major role in shaping the early careers of the most prominent alcohol researchers across North America. Since our founding in 1982, we have maximized our impact as a relatively small foundation by centering the grant program on novel research proposals put forth by the most promising investigators. Recently funded research projects which are described below offer an exciting opportunity to view the future through the studies currently underway by Foundation grantees.
Behavioral and Social Advisory Council
Charlotte A. Boettiger, Ph.D., University of North Carolina at Chapel Hill, “Neural circuit bases of impulsive choice in emerging adults and heavy drinking adults.”
It is well established that people with a history of alcohol abuse have a stronger tendency to choose smaller, immediate rewards over larger, delayed rewards relative to people with no history of substance abuse. We have recently found that two groups at risk for developing substance- use disorders share this tendency: late adolescents and heavy drinking adults who do not meet clinical criteria for a substance-use disorder. It is presently unknown whether this common behavioral tendency of these two high-risk groups reflects shared or unique underlying neurobiological mechanisms. As differing underlying causes may call for differing intervention strategies, answering this question may have important practical implications for treating and preventing alcoholism and other substance-use disorders. The proposed studies will use cognitive neuroscience tools, including functional magnetic resonance imaging (fMRI), to investigate the neurobiological bases of impulsive decision making in late adolescents and heavy drinking adults to address this question. We hope that this work will ultimately make a substantial contribution to our understanding of the causes of alcoholism and other substance-use disorders.
Julia Braverman, Ph.D., Cambridge Health Alliance, “The effect of tailoring a testimonial message on excessive drinking by personal relevance on implicit and explicit narrative persuasion.”
Research suggests that narrative persuasion (i.e., telling vivid stories to promote attitude change) might be an effective public health promotion technique. However, it is unclear whether making a narrative story more personally relevant increases its persuasiveness. This research program explores this possibility for excessive alcohol consumption. It is well known that alcohol abuse impairs various domains of life, e.g., health, social relationships, and career. The importance of these domains varies from person to person. Hence, some people are typically more concerned about their social relationships, whereas others pay more attention to their career, or health. We examine the effect of matching the message content to what individuals find most personally relevant with two experiments. For the first experiment, we will ask participants randomly assigned to read personally relevant, or not, stories about alcohol. We will determine whether matching personal relevance along three domains (relationships, career, or health) positively affects individuals’ psychological immersion into the story, alcohol-related attitudes, and self-reported drinking. For the second experiment, we will use a priming technique to make a specific domain temporarily more salient (i.e., “activated”) to an individual. This will allow us to investigate if induced relevance to self can yield similarly positive alcohol-related health outcomes.
Abby Goldstein, Ph.D., University of Toronto, “Examination of a developmental model of alcohol use and alcohol problems in emerging adulthood.”
The purpose of this study is to better understand how attachment styles (i.e., a mental model of relationships that emerges from early relationships with caregivers), difficulties regulating emotions, and problems in interpersonal relationships influence drinking in emerging adulthood (ages 18-25), a period of increased risk for alcohol use and drinking problems. Difficulties in these areas are particularly important for emerging adults because early experiences with primary caregivers influence how individuals respond to distress, seek support, and connect with others during developmental transitions. To date, there is little research on the relationship between these variables in emerging adults, and no research on this topic has studied people from day-to-day. We will recruit 200 emerging adults (ages 18-24) and assess these relationships across one year and over 28 days using online daily diaries. We predict that emerging adults with insecure attachment styles will have problems with emotion regulation and interpersonal difficulties, which will contribute to increased alcohol use and problems over time. From day-to-day, we anticipate that people with emotion regulation difficulties will drink more alcohol and experience greater alcohol problems on days when they are in a negative mood, whereas those with interpersonal difficulties will consume more alcohol and experience greater alcohol problems on days when interpersonal stress is high. Findings from this study will have important implications for intervention, with the goal of identifying who would benefit most from treatment and establishing specific intervention targets.
Derek K. Iwamoto, Ph.D., University of Maryland, “The role of feminine norms on prospective alcohol use among underage Asian-American and Caucasian women.”
The dramatic increase in alcohol misuse by underage (18-19) young adult women signals a growing similarity of alcohol-use patterns and behaviors to men. Alcohol use among Asian American women in particular has been escalating at an alarmingly high rate over the past decade. This presents an emerging public health concern as women often experience alcohol-related problems disproportionate to men’s level of use. It is essential to understand the gender socialization factors that contribute to this rise in alcohol use among Asian American women, with particular emphasis on the peak age of use during late adolescence. One important gender socialization factor, feminine norms, or expectations about how women are supposed to act, think, and feel may better explain why certain women drink more than others. Feminine norms appear to differ between Asian American and Caucasian women, and may be especially relevant to Asian women given that this group is often stereotyped as hyperfeminine-i.e., being viewed as “sexually exotic” and “submissive” by society. The aims of the study are to develop a core understanding of the key theory-driven feminine norms factors on prospective alcohol misuse and related problems, and to test the specificity of this model with 500 Asian Americans and Caucasian women by examining racial differences in predictors and patterns of alcohol misuse over the course of a year. Findings from this study will provide a more comprehensive theoretical understanding of similar and different developmental trajectories of risk between female Asian Americans (an under-studied population) and their Caucasian counterparts.
Sarah L. Pedersen, Ph.D., University of Pittsburgh, “Implicit alcohol cognitions and disinhibition: A pathway to alcohol problems.”
The decisions made while drinking directly influence the likelihood of experiencing alcohol-related problems, yet little research has examined this topic. The current study integrates two widely studied risk factors for alcohol use. First, I am examining alcohol cognitions or what one expects will happen when people drink alcohol. Research has highlighted the importance of studying not only these cognitions but also the processing system by which these cognitions are accessed. For example, relying on a “hot” or fast acting processing system may increase risk for heavy alcohol use because the individual does not rationally think through the negative consequences that could occur from heavy drinking. Second, I am examining disinhibition (impulsivity). The current study examines these constructs while participants are both sober and acutely intoxicated. The primary goal is to test if individuals who experience the most sensitivity to the disinhibiting effects of alcohol rely more on their “hot” cognitive processing system when making decisions while intoxicated within a given drinking event. This study will increase our understanding of risky decisions made while drinking (e.g., driving after drinking, drinking more than intended) that lead to problems and ultimately may inform intervention efforts for individuals with high levels of disinhibition.
Brian A. Primack, M.D., Ph.D., University of Pittsburgh, “Systematic analysis of alcohol-related content in social media.”
Prior research has shown links between watching alcohol-related content in traditional media—such as television, movies, and music—and having alcohol-related problems. However, little research has focused specifically on the content of internet audiovisual media. This is an important gap, because internet media are a highly accessible source of audio-visual information for impressionable adolescents and young adults. Internet media may be particularly influential because they combine the compelling production values of traditional media with personal involvement through discussion and commentary among viewers. Therefore, we will undertake a systematic analysis of alcohol-related content on YouTube, which is consistently the leading source of internet audio-visual information for our population of concern. We will focus on (1) the audiovisual content of the most popular alcohol-related videos; (2) accompanying viewership metrics such as the number of ‘likes’ and ‘dislikes’; and (3) commentary and discussion surrounding the videos. The knowledge we gain from this research will lay the foundation for definitive future studies assessing the impact of these new media messages on important alcohol-related problems, such as binge drinking and driving under the influence.
Tomoko Udo, Ph.D., Yale University, “Is ghrelin associated with alcohol craving and self-administration in alcohol-use disorders.”
Ghrelin, an appetite-stimulating hormone, has been suggested as a potential therapeutic target for alcohol use disorders (AUD). Preclinical studies report changes in ethanol consumption after pharmacological or genetic manipulation of ghrelin. In humans, ghrelin has been linked with alcohol craving and treatment outcomes, but the association of ghrelin levels with alcohol consumption remains unclear. Management of alcohol craving is an important component of AUD treatment, but medications are less likely to have clinical significance unless they facilitate abstinence or reduce harmful drinking. The proposed project will specifically address whether ghrelin is related to the risk for heavy drinking under heightened craving state in drinkers with AUD. This study will use a well-validated human alcohol self-administration paradigm that models alcohol consumption following a low dose of alcohol designed to increase craving for further alcohol consumption. We hypothesize that ghrelin is positively correlated with: 1) the number of drinks consumed during self-administration, 2) alcohol craving during the alcohol priming and self-administration sessions, and 3) the subjective reward effects of alcohol. The study will also explore the moderating role of sex and smoking status in the ghrelin-alcohol use relationship. Positive findings will provide a foundation to evaluate Phase II ghrelin antagonists for the treatment of AUD.
Jacquelyn D. Wiersma, Ph.D., University of Arkansas, “Alcohol use and interpersonal relationships: Pathways from adolescence into young adulthood.”
Despite the many prevention efforts directed at reducing adolescent alcohol use, one area of research that has been ignored is the romantic partner context. Although experimenting with alcohol and romantic partnerships increases over adolescence, no research to date has examined adolescent drinking behaviors in the context of their romantic partnerships. Without such research, it is impossible to identify profiles of adolescent drinking partnerships, selection and socialization effects of romantic partners on alcohol use, and the influence of experience in drinking and adolescent romantic partnership on later young adult outcomes. The overarching goal of this project is to investigate the impact of alcohol use in adolescent romantic relationships and the implications that these drinking partnerships may have on young adult outcomes. Data come from The National Longitudinal Study of Adolescent Health (Add Health), a three-wave longitudinal survey of a nationally representative sample of adolescents continuing into young adulthood. The results will provide information about adolescent romantic drinking partnerships, factors associated with selection into these partnerships, and how these partnerships are associated with young adult behaviors. The results will provide a starting point from which to develop more focused and relevant peer and romantic-based interventions to reduce adolescents’ alcohol use.
Medical Advisory Council
Dian J. Chiang, M.D., M.P.H., Cleveland Clinic Foundation, “Complement system and polymorphisms in alcoholic steatohepatitis: From animal model to human.”
Alcoholic steatohepatits (ASH) is one of the leading causes of chronic liver diseases and liver fibrosis. There is little insight in the interaction of alcohol and host genomic profile to allow prediction of individual susceptibility to ethanol-induced liver injury. Further, the response to current treatment remains poor. A novel intervention strategy that would not only decrease inflammation, but also enhance tissue repair and preserve the ability of the patient to resist infections, is in great need. Emerging evidence supports the critical role of complement in both liver inflammation and regeneration. However, the control and coordination of these two complement-mediated processes remains largely unknown. The primary objectives of this proposal are to investigate the therapeutic effect and downstream mediators of C1 inhibitor in animal models of ethanol-induced liver injury and the mechanism by which complement modulates the response of hepatocytes to injury in hepatocytes. Further, we will determine the role of genetic polymorphisms affecting complement activation in the susceptibility and severity of ASH in patients. Cumulative genetic risk from variance in complement pathway and gene-gene interaction will be determined. The results will facilitate translation of the pre-clinical studies into development of individualized patient care in ASH.
Nicholas W. Gilpin, Ph.D., Louisiana State University HSC, “Role of melanocortin-4 receptors (MC4Rs) in chronic alcohol-induced changes in thermal sensitivity.”
Approximately 30% of Americans report chronic, recurrent, or long-lasting pain, and epidemiological studies suggest that between 20-50% of U.S. adults with chronic pain use alcohol to self-medicate. Alcohol reduces pain (i.e., produces analgesia) but this effect fades as tolerance develops with repeated alcohol use. On the other hand, alcohol withdrawal is defined by increases in sensitivity to painful stimuli (i.e., hyperalgesia). These factors set the stage for gradually increasing alcohol use coupled with gradually decreasing efficacy of alcohol in relieving pain, as well as worsened pain outcomes in the absence of alcohol. Melanocortin-4 receptors (MC4Rs) are found in the brains of humans and animals. Interestingly, activity at these receptors modulates alcohol drinking in rodents, and also modulates tolerance to the analgesic effects of opiates. The proposed experiments will use rodent models to explore: (1) how alcohol withdrawal alters sensitivity to a painful stimulus, (2) how the analgesic effects of alcohol are altered during alcohol dependence, and (3) the role of brain MC4Rs in hyperalgesia and excessive alcohol consumption during alcohol dependence. These experiments will provide the foundation for studies on the role of pain in excessive alcohol drinking, and studies of alcohol effects in the presence of chronic neuropathic pain.
Christopher Lapish, Ph.D., Indiana University, “Targeting the prefrontal cortical dopamine system in excessive drinking.”
Understanding the changes in brain function that underlie alcoholism is critical for devising novel treatment strategies for this disease. The neurotransmitter dopamine plays a central role in guiding motivated behaviors and influences the ability of evolutionarily advanced brain regions, such as the prefrontal cortex, to integrate information. This is especially relevant for alcoholism as individuals in advanced stages of this disease exhibit an inappropriately large increase in brain activity in the prefrontal cortex when exposed to environmental stimuli that could potentially trigger relapse. This project will examine if targeting the prefrontal cortex dopamine system provides an effective way to mitigate alcohol-seeking behaviors. To this end, we will make real-time measurements of brain activity in validated preclinical rodent models of alcoholism that are seeking and drinking alcohol. With these data we will assess how communication between brain regions that interact with the prefrontal cortex are altered during these behaviors and determine if manipulating the dopamine system in this brain region suppresses excessive drinking. With this information we will better understand the changes in brain function that underlie excessive alcohol seeking and if the prefrontal cortex dopamine system presents a viable target for treatment development.
Mariana Lazo, Ph.D., M.D., Sc.M., Johns Hopkins University, “The role of moderate alcohol consumption in nonalcoholic fatty liver disease.”
Nonalcoholic fatty liver disease (NAFLD) is estimated to affect more than 30 million Americans. Although heavy alcohol consumption is a well-known cause of fatty liver, few small recent studies suggest that light or modest alcohol consumption may instead have protective effects. To date there are inconsistent expert opinions and clinical guidelines on acceptable doses and the safety of alcohol consumption among patients with fatty liver. The proposed project will examine the association between low-moderate alcohol consumption and NAFLD with more detail. We will investigate the role of patient level characteristics including sex, race, genetic predisposition and underlying medical co-morbidities as modifiers of the observed effects of alcohol on NAFLD. We hypothesize that while modest alcohol consumption is associated with lower risk of fatty liver, this benefit is not universal and is further influenced by demographic, genetic, medical, and lifestyle factors. Findings from this project will help the development of clinical guidelines for patients with NAFLD and provide information regarding preventive strategies among people at risk for NAFLD.
Christopher M. Snyder, Ph.D., Thomas Jefferson University, “Testing the impact of CMV infection on the progression of alcoholic liver disease.”
While most heavy drinkers develop fatty liver disease, the mechanisms driving progression to more severe diseases such as alcoholic hepatitis and cirrhosis are still unclear. Alcoholic hepatitis is a particularly severe inflammatory disease that develops in up to 35% of heavy drinkers. Interestingly, severe hepatitis is absent from animal models of alcohol consumption unless a secondary stressor is supplied, suggesting a role for environmental factors in disease progression. Cytomegalovirus (CMV) is a ubiquitous herpesvirus that infects the liver, among other organs, in approximately 60%-80% of Americans and most people in the world. CMV persists for life in its host by establishing latency (viral persistence without gene expression). However, CMV can periodically reactivate from latency, necessitating continuous immune surveillance to keep the host disease-free. Critically, CMV reactivation from latency is promoted by inflammation. Chronic alcohol consumption causes inflammation and simultaneously impairs immune function, both which might lead to CMV reactivation and exacerbated liver disease. Yet, the impact of CMV on alcohol-induced liver disease is unknown. The goal of this project is to determine whether chronic alcohol consumption leads to CMV reactivation using a mouse model and to test whether CMV contributes to the progression of alcoholic liver disease.
Lingjun Zuo, M.D., Ph.D., Yale University School of Medicine, “Post-GWAS search for risk loci for alcohol and nicotine co-dependence using third-generation sequencing.”
Individuals with alcohol and nicotine dependence continue to use alcohol and nicotine despite adverse consequences in health, job and family functions. Evidence demonstrates that genetic factors constitute a significant cause of alcohol and nicotine co-dependence. Dr. Zuo scanned the whole genome and narrowed the significant risk signals for alcohol and nicotine co-dependence to the IPO11-HTR1A region. This region is enriched with replicable significant association signals and functional signals in two European-origin populations. It is thus postulated that there is a causal variant(s) for this disorder in this region. Deep sequencing of this region is an important strategy to search for the causal variant(s). In this proposed study, Dr. Zuo will apply the 3rd-generation sequencing technology to sequence this region. This technology is a breakthrough evolution for the 2nd-generation sequencing and a cost effective, high-speed, superior-quality and powerful cutting edge technology. If this proposal is successful, this will represent substantial progress in the research field of the etiology of alcohol and nicotine dependence. Results are likely to have a significant impact on the understanding of variation in genes in alcohol and nicotine co-dependence, helping us to better understand the biological basis of this disorder.
Please refer to the links below for grants project profiles from previous years: