NIAAA Funded Research



The highest rates of fetal alcohol spectrum disorders (FASD) in the world have been found in these South African (ZA) towns and their surrounding rural areas where comprehensive prevention research has been ongoing for the past four years. Epidemiology research preceded the prevention for a decade and it is also ongoing. Population-based rates of specific FASD diagnoses in the most recent wave already finalized for the prevention community (Wellington IV) were: 94 per 1,000 for fetal alcohol syndrome (FAS), 56 per 1,000 for partial fetal alcohol syndrome (PFAS), and 30 per 1,000 for alcohol-related neuro-developmental deficits (ARND). In another finalized wave of the comparison areas (BRAM I), the rates were even higher: 61, 46, and 30 per 1,000 respectively for FAS, PFAS, and ARND. Rates of FASD have been persistently high in this region, and our clinical team's ability to diagnose the full spectrum for children age 6-20 years is now proficient. Because of the high prevalence of FASD in these communities, and the extensive epidemiology studies ongoing there, prevention and intervention research can be effectively instituted and evaluated for efficacy.

Furthermore, new research trials and etiologic research can now be instituted in a systematic, productive, and potent manner for a refined understanding of FASD across the lifespan and to inform basic science. Improved understandings about the specific characteristics and patterns of FASD in these ZA populations have broad implications for public health in most every human population. With this continuation application, we seek to initiate: 1.) early intervention research (developmental and nutritional) for children as young as 24 months of age that may reduce or ameliorate many of the negative effects of prenatal alcohol exposure in an already-identified cohort of children (FASD and controls); 2.) a comparative study of results from alcohol biomarker (EtG and FAEE) tests and self-reported alcohol use in the prenatal period; and 3.) a detailed case control study of maternal nutrition in the prenatal period.

We will continue to research the developmental trajectory of FASD from birth to 7 years in the above cohort and recruit a new newborn cohort. Understandings from these younger children will add to data already collected in multiple, other, cross-sectional studies to inform us about FASD from birth to 23 years. All proposed research is both feasible and possible by continuing Institute of Medicine (IOM)-recommended prevention services and efficacy research, targeting especially the selected and indicated levels established and provided by our current team living and working in the communities. Finally, to fully evaluate the net effect of the comprehensive prevention over 9 years, we will repeat linked evaluation (community survey and in-school prevalence studies) to assess any impact the overall prevention model, particular prevention techniques, and participatory research may have had on risk factors for and actual rates of FASD.

Etiology, maintenance, and recovery from alcohol use disorder (AUD) are each highly heterogeneous processes, and variability in the clinical course of AUD poses challenges for the development of effective treatments. Recently proposed models of AUD heterogeneity are informed by neurobiological mechanisms underlying the development and maintenance of alcohol use. Different measures of reward/relief drinking have been used across studies, the construct validity of these measures has not been thoroughly assessed, and scoring guidelines to identify reward/relief drinkers do not exist. To address these methodological issues and gaps in the literature, the primary goal of the proposed project is to validate a brief measure of reward/relief drinking that can be easily administered and scored in clinical practice.  (Learn more)

Numerous evidence-based behavioral and pharmacological interventions have been developed and some have been adopted by alcohol treatment providers, however very little is known why specific treatments are effective (i.e., what are the mechanisms of behavior change in treatment) and which treatments are most effective for specific individuals. Despite an increased focus on mechanisms of behavior change among alcohol researchers over the past 15 years, many findings have not been replicated and an evidence-based understanding of why and for whom individual treatments for alcohol use disorder (AUD) are effective remains elusive. First, it is clear that AUD is heterogeneous in both etiology and outcomes following treatment, yet heterogeneity in mediators of AUD treatment has not been considered, mostly because of methodological limitations. In general, the mechanisms of behavior change following alcohol treatment are not well understood. Second, AUD treatment studies investigate multiple mechanisms of behavior change. One issue is a lack of understanding and methodological techniques to test which mechanism of behavior change is robust if it were to be replicated under a different set of conditions (e.g., different participants with different mechanisms of behavior change).

To address these gaps in understanding, this study will build an empirical knowledge base by identifying robust mechanisms of behavior change (i.e., do mechanisms replicate across different participants?) and by modeling heterogeneity in alcohol treatment (i.e., for whom it works/fails to work) through development and application of the state-of-the-art methodological techniques, extensive analyses of eleven existing randomized clinical trials for AUD, as well as simulation studies based on AUD clinical trial data. Candidate mechanisms of behavior change, based on prior studies and the dynamic model of relapse as a guiding theoretical model, will include self-efficacy, craving or urges to drink, mutual help involvement, social support, therapeutic alliance, client language, and coping responses. Results from the proposed study will inform an individualized approach to formulating treatment recommendations, clarify which treatment mechanisms (mediators) are most robust across studies, and directly inform clinical decision making. In addition, the proposed study will provide an extensive suite of data analytic tools that will be designed specifically to answer questions regarding (a) testing robustness of candidate mediators, and (b) testing mediation in the presence of heterogeneity. The analytic tools will accommodate features of data commonly observed in AUD clinical trials and will be accessible to substantive researchers with knowledge of regression and mediation. The ultimate goal of this study is to yield a better understanding of mechanisms of AUD treatment outcomes in order to inform precision medicine initiatives.

The training program, initiated in 2010, has trained 26 pre- and postdoctoral trainees for careers in alcohol research. Support is provided for 4 pre-doctoral trainees, drawn from the Department of Psychology, and 3 post-doctoral trainees from disciplines relevant to the goals of the training program, such as psychology, sociology, psychiatry, social work, population health, and economics. The training program prepares future scientists to develop and test effective models for impacting change in alcohol use through improved approaches to treatment and indicated prevention, to conduct research on processes of change in drinking behavior, and to develop and test models to disseminate knowledge of effective interventions and change processes to diverse populations.  (Learn more)

High priority has been assigned to the investigation of what actually occurs in AA, with a special focus on identifying prescribed AA behaviors and processes that are predictive of drinking reduction. This study will generate, for the first time, a comprehensive and definitive process model of AA-related behavior change. This objective will be realized through the highly innovative use of EMA data collection among early AA affiliates. Aim 1 will determine if four MOBC identified by AA researchers mediate the linkage between three types of AA prescribed behaviors and drinking outcome. Noteworthy, these analyses will include the first rigorous testing of six of seven of Kazdin's (2007) criteria to confirm (or reject) that these four statistical mediators are MOBC. Aim 2 will investigate whether the actions of the AA active ingredients on mediators (a path) and the actions of the mediators (b path) are constant over time or, alternatively, if there are critical periods of influence. Last, aim 3 will determine if the four MOBC operate differently across distinct subpopulations.  (Learn more)

Alcohol use disorder (AUD) is a significant public health problem, yet treatments demonstrate only modest efficacy, likely due to the the profound phenotypic heterogeneity of AUD. In order to improve the efficacy of AUD treatments, it is imperative to better characterize this heterogeneity which may, in turn, elucidate clearer treatment targets for precision medicine approaches. This likely requires shifting conceptualizations of AUD away from clinical description and towards etiologic mechanisms, an approach embodied by the goals of some modern conceputalizations of AUD, such as the Addiction Research Domain Criteria (AARDoC) and Addictions Neuroclinical Assessment (ANA). However, current research suggests that AARDoC and ANA suffer from important shortcomings, including limited clinical efficiency, and may therefore benefit from further development, refinement, and validation. To address these shortcomings, the proposed project aims to (a) empirically test the models articulated by modern conceptual AUD etiological frameworks, including the ANA, and (b) derive a mechanism-based computerized adaptive test (CAT) assessment of AUD developed using principles of objective test construction and community-based participatory research strategies. First, a candidate set of self-report items indexing 13 etiologic domains articulated by the Etiologic, Theory-Based, Ontogenetic Hierarchical (ETOH) framework of AUD mechanisms, which serves as a recent extension of AARDoC/ANA, will be derived from the literature and two rounds of cognitive interviews will be used to refine the item set among a diverse group of participants (N = 50) with hazardous or harmful alcohol use. Next, items will be administered to a combined community and clinical sample (N = 1,200) to empirically test the structure of items and determine the best-fitting model.

Item response theory will then be used to calibrate the items for the purpose of building a CAT for each of the domains identified (e.g., reward, cognitive control, negative emotionality). Using the refined and calibrated item set and domain-specific CATs, data will be collected from an additional independent sample of heavy drinkers (N = 100). Ecological momentary assessment over 14 days and a follow-up assessment will also be conducted with the goal of evaluating the psychometric properties of the CATs in ecologically valid contexts and over time. Specifically, to determine if the domain-specific CATs demonstrate validity (e.g., convergent, discriminant, predictive) and reliability (e.g., test-retest) across diverse patient populations and sex/gender groups. All research aims will be conducted alongside and in consultation with individuals with lived experience of AUD to ensure the measure is acceptable, feasible, and adequately contextualized. This project is consistent with NIAAA's Strategic Plan, specifically Goal 1 (Identify mechanisms of alcohol-related pathology) and Goal 2 (Improve diagnosis and tracking of AUD). The resulting measure also has the potential to support progress towards Goal 4 (Develop and improve treatments for AUD) by facilitating the assessment of mechanisms that may serve as viable targets in AUD treatments, including behavioral and pharmacological interventions.  (Learn more)

Alcohol misuse among young adults in the U.S. is a significant public health concern. Protective behavioral strategies (PBS) are cognitive-behavioral strategies used before, during, or immediately after drinking to reduce alcohol use, intoxication, and/or alcohol-related harms. Using PBS appears to be an effective means of harm-reduction, though PBS-based interventions are unlikely to have reached their full potential. Self-determination theory (SDT) is a general theory of human motivation that has been applied to understand a wide range of health-promoting behaviors, though its application to alcohol research has been limited. SDT proposes that there are different types of motivation that vary in the extent to which they are self-determined. Our objective is to use an ecological momentary assessment (EMA) design to investigate the tenets of SDT to better understand PBS use. (Learn more)

Although modestly effective treatments exist for alcohol use disorders (AUD), many individuals relapse to heavy alcohol use after completing treatment, suggesting the need for a better understanding of factors that contribute to successful outcomes. Whereas much of the focus in past studies has been on identifying what treatments work for AUDs, only recently has there been a focus on why particular treatments work, and the mechanisms by which treatment leads to changes in drinking. This focus on mechanisms of behavior change (MOBCs) has the potential to not only allow for an accumulation of knowledge about the process by which treatment leads to better outcomes, but also may lead to the development of new treatments or modifications of existing treatment approaches that target empirically supported mechanisms known to lead to change. Existing research has focused on potential mechanisms including alcohol cue reactivity, affect regulation, and behavioral control, but these constructs have largely been tested using self-report measures, and there is a noticeable paucity of studies that examine these mechanisms from a neurocognitive perspective. To address this gap in knowledge, the proposed study will examine MOBC at multiple levels including self-report, behavioral performance, and neural network engagement, with a focus on the function of the lateral and medial frontal control networks, striatal based reward networks, and amygdala networks underlying emotional reactivity.

One hundred eighty treatment-seeking individuals with an AUD will be randomized to receive either 8 weeks of Cognitive Behavioral Treatment (CBT) or Mindfulness Based Treatment (MBT) after receiving 4 weeks of a platform treatment that focuses on enhancing motivation to change. To establish the temporal relationship between changes in drinking and changes in these MOBCs, patients will be assessed at: (a) baseline; (b) four weeks into treatment; (c) immediately post-treatment; and (d) 9- and 15-months post-baseline. Self-report measures and behavioral tasks will be administered at monthly intervals during treatment; and fMRI will be collected at baseline, and at 3, and 9-months post baseline. Relationships between changes in drinking and changes in the proposed MOBCs will be examined using advanced mixed modeling techniques that have been pioneered by the research team. Further, the project will leverage data collected in a separate project examining MOBC in a non-treatment seeking sample using the same measures collected at similar timepoints. By identifying MOBCs of CBT or MBT that differentially contribute to changes in drinking, the proposed project will not only derive a deeper understanding of successful behavior change, but also may inform the development of novel treatments for AUD. In addition, by identifying neurocognitive factors predictive of successful change, it may be possible to utilize this knowledge to match specific treatments with particular patient neurocognitive profiles.

The alcohol and addiction research domain criteria (AARDoC) has been proposed to provide a framework for understanding the nature of alcohol use disorder (AUD) in terms of psychological and biological constructs that can be traced to a specific behavioral function with an underlying biological basis (e.g., neural dysfunction). The AARDoC proposes that AUD develops, progresses, and is maintained because of heightened incentive salience for alcohol, greater negative emotionality, and/or impairments in executive functioning and impulsivity. This study will build an empirical knowledge base regarding clinical assessments that could be used to identify the AARDoC constructs and will examine whether the AARDoC constructs are associated with a novel typology of alcohol recovery, defined by consumption and functioning, among individuals who receive alcohol treatment. To achieve the study aims, integrative data analysis of AARDoC constructs among more than 3600 individuals (n = 3,672) who participated in three publicly funded alcohol treatment studies will be examined. (Learn more)
There has been a broad movement in psychological science, stemming from the Research Domain Criteria initiative by the National Institute of Mental Health, to study the core features of mental disorders by integrating data across levels of information ("from genomics and circuits to behavior and self-report"). Given the vast heterogeneity among those with alcohol use disorders (AUD), there has been a recent call to establish a similar Alcohol and Addictions Research Domain Criteria (AARDoC). Investigators at the National Institute on Alcohol Abuse and Alcoholism have proposed the Addictions Neuroclinical Assessment (ANA) as an organizing framework for carrying out AARDoC research, with the goal of establishing a common assessment battery to be used by researchers and clinicians. The aims of the proposed research study will fill important gaps in the literature by validating the three ANA domains in a new and diverse sample of individuals with AUD (Aim 1), examining how the ANA domains relate to drinking behavior at baseline as well as how changes in ANA domains relate to changes in drinking over a three-month time period (Aim 2), and, as an exploratory aim, evaluating sex differences in ANA domains and sex differences in the relationship between drinking and ANA domains (Aim 3).  (Learn more)