2014 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.
Matthew Pearson, Ph.D., University of New Mexico, “Affective dynamics and alcohol outcomes: An ecological momentary assessment study.”
Although conventional wisdom and scientific theories alike posit relationships between mood/affect and alcohol use, the testing of affect regulation models of alcohol use is incomplete at best. Following a trend in numerous fields to more carefully examine affective dynamics, or the way in which affect changes and unfolds over time, the proposed study will examine multiple distinct statistical operationalizations of affective dynamics to 1) examine whether affective dynamics predict alcohol-related outcomes, and 2) compare and contrast the predictive validity of distinct operationalizations of affective dynamics. It is expected that affective dynamics variables will uniquely predict alcohol-related outcomes (above and beyond level of affect) including alcohol use, alcohol consequences, and alcohol-use disorder symptoms. It is also expected that affective instability measures (i.e., Mean Square of Successive Differences) that account for both affect variability and temporal dependency will have the strongest relationships with alcohol use and alcohol consequences. In addition to these primary aims, the present study will also be able to examine several secondary aims including what moderates these relationships between affective dynamics and alcohol outcomes (e.g., drinking motives, self-regulation), and how alcohol use may predict subsequent affective dynamics.
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.
Martin Plawecki, M.D., Indiana University, “Alcohol exposure rate control.”
The way some people consume alcohol–how much, how often, and how quickly–is riskier than others. While the definition of heavy or “at risk” drinking only includes quantity and frequency, the NIAAA also recommends against drinking too quickly when addressing binge drinking. Currently available procedures to study binge drinking are generally limited by safety concerns and cannot reliably control how quickly an individual becomes intoxicated. This research aims to overcome that inability through an intravenous alcohol delivery method that allows a subject to precisely control his/her rate of increase of breath alcohol concentration (BrAC). The subject can choose a new rate of BrAC change every three minutes, and we track their trajectories of BrAC and subjective perceptions throughout a 2-hour laboratory session. The short-term goal is to find out if binge drinkers prefer higher rates of increasing BrAC, compared to heavy but non-binge drinking control subjects. A successful outcome will validate a new laboratory measure that correlates well with binge drinking history and thus risk for developing an alcohol use disorder. We would then investigate the mechanisms underlying the phenomenon and develop interventions to reduce the rate at which binge drinkers self-administer alcohol.
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.
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.
Kazue Hashimoto-Torii, Ph.D., Children’s Research Institute, “Heterogeneous activation of stress response signaling in the brain by fetal alcohol exposure.”
The proposed study will test whether variation in activation of a stress responsive signaling among fetal brain cells explains variation in pathological outcomes of brains following prenatal alcohol exposure. To this end, we will first determine if heterogeneous activation of the stress responsive signaling is related to regionally specific vulnerability of brain cells to alcohol. Then we will produce a new reporter transgenic mouse model to identify the descendants of the fetal brain cells with higher level of the activation, allowing us to determine how the differences in activation level of the stress responsive signaling may affect eventually the pathophysiological status of the brain cells in mature brain.
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.
Brian N. Mathur, Ph.D., University of Maryland School of Medicine, “Ethanol modulation of nucleus accumbens inhibitory microcircuits.”
This research proposal investigates how ethanol exposure induces brain circuit remodeling to result in elevated ethanol consumption. The nucleus accumbens (NAc) is a brain region that strongly controls reward seeking. Motivated behavior for rewards such as ethanol is dependent upon plastic changes at neuronal synapses within the NAc that are controlled by endogenously released cannabinoids (endocannabinoids). In several brain regions, ethanol is known to increase endocannabinoid tone. Endocannabinoids signal through the cannabinoid type 1 receptor (CB1), a protein that mediates synaptic depression, a form of synaptic plasticity. CB1 is localized to a subpopulation of NAc neurons that powerfully inhibit NAc output. Thus, we hypothesize that CB1-mediated depression of inhibitory neuron synaptic transmission disinhibits the NAc to mediate ethanol elevated ethanol consumption over time. We will test how acute and chronic ethanol exposure interacts with the endocannabinoid system to remodel inhibitory synapses to promote ethanol reinforcement using electrophysiological, genetic, and behavioral techniques in mice. The results of this study may provide novel therapeutic strategies for the prevention of alcohol dependence.
Zoe McElligott, Ph.D., University of North Carolina at Chapel Hill, “Role of amygdalar neurotensin neurons in alcohol drinking.”
My research focuses on neuronal circuitry at the intersection of alcoholism and anxiety disorders. Previous work has shown that alcohol can modulate the activity of certain areas in the brain; however, most of these areas are complex mixes of cell types and scientists are only beginning to understand how these cells function under varying circumstances. My research suggests that neurons of one cell type, neurotensin neurons in a well-known anxiety center named the central nucleus of the amygdala, mediate rewarding properties of alcohol. In this proposal I will test the hypothesis that alcohol activates and modulates these neurons. Further, I will examine the effects of repeated exposure to alcohol on the physiology of these neurons. In addition to providing insights into brain microcircuitry related to alcoholism and anxiety disorders, this research will hopefully provide insight to potential new targets for the development of therapeutic treatments for alcoholism.
James J. Prisciandaro, Ph.D., Medical University of South Carolina, “An investigation of disturbances in glutamatergic neurotransmission in frequent heavy episodic drinkers.”
Heavy episodic drinking (consuming 4+/5+ alcoholic beverages, for women/men respectively, over a relatively brief period of time) disproportionately characterizes young adult alcohol consumption and is a major public health concern. Research in individuals with advanced alcohol dependence has demonstrated neurochemical disturbances (particularly involving the excitatory neurotransmitter, glutamate) that are highly dynamic during early abstinence from alcohol and that are directly implicated in compulsive alcohol use, craving, and risk of relapse. Demonstrating similar disturbances in young, frequent heavy episodic drinkers may provide greater insight into the transition between heavy young adult drinking and later, advanced alcohol dependence that could be used to predict and prevent this transition as well as to develop novel strategies to reduce the negative consequences of problematic drinking in young adults. The present study will repeatedly measure in vivo concentrations of neurochemicals implicated in alcohol dependence, including glutamate and gamma-Aminobutyric acid, using state of the art two-dimensional proton magnetic resonance spectroscopy in a group of frequent heavy episodic drinkers and a group of light drinker comparators following a discrete period of monitored abstinence from alcohol.
Please refer to the links below for grants project profiles from previous years: