Organization | NIAAA

Epidemiology of Alcohol Problems: Alcohol-Related Disparities Research Center

The Alcohol Research Group's Alcohol Research Center has contributed major conceptual and methodological advances for over 40 years. The Center studies the complex interactions between drinking patterns across the life-course, demographic characteristics, sociocultural and drinking contexts, community and policy factors, and alcohol-related problem and services outcomes, both in the general population and with attention to high-risk groups.

Environmental Approaches to Prevention Alcohol Research Center)

The Prevention Research Center's long-running Alcohol Research Center takes a multidisciplinary approach to prevention research that emphasizes integration across theories from the biological to the behavioral and social sciences to enhance understanding of the causal impacts of drinking environments on drinking patterns and problems. Over the past four decades the Center has led research into the development of community-based approaches to the prevention of alcohol abuse and related problems, focused upon assessments of the impacts of local, state and national alcohol policies on alcohol sales and population outcomes related to use (e.g., motor vehicle crashes and violence), and developed social ecological models of youth and adult use and problems that elucidate the impacts of environmental conditions on youth, young adult, and adult problems related to alcohol.  These contributions have directed research toward the fundamental contributions that alcohol and other drug environments make to population and individual risks for heavy alcohol use, abuse, problems and alcohol use disorders.

The Alcohol Policy Information System (APIS) is an online data resource that provides authoritative, detailed, and comparable information on alcohol-related policies at the state and federal levels in the United States based on primary legal research on the statutes and regulations. APIS was developed by DEPR to facilitate research on the effects and effectiveness of alcohol-related public policies. APIS provides detailed coverage, including exact effective dates and legal citations, for 36 specific policy topics in 10 categories. For every policy topic, APIS provides detailed comparison tables showing both up-to-date policy information and policy changes over time with exact effective dates. APIS also provides descriptive overviews, maps and charts, summaries of relevant federal law, and detailed explanatory notes. APIS also covers laws and regulations addressing cultivation, sale, and use of recreational (i.e., non-medical) cannabis in states that have legalized these activities. Special coverage is also provided of state policies affecting alcohol availability adopted in response to the COVID-19 pandemic.

Surveillance Reports periodically examine trends in apparent alcohol consumption, underage drinking among youth ages 12–20 years, and liver cirrhosis mortality in the United States. Alcohol Epidemiologic Data Reference Manuals are statistical compendia of alcohol-related data useful to researchers and others interested in alcohol problems. The Alcohol Epidemiologic Data Directory provides a listing of surveys and other relevant data suitable for epidemiologic research on alcohol. Most data sets described in this document are national in scope. In some cases, however, select specialized data sets may be included. Information on the availability of and access to the data sets is provided.

COGA is a comprehensive research project on the inherited aspects of alcohol use disorder (AUD) with the goal of identifying genes that influence an individual’s risk of developing alcohol problems, and understanding how that risk unfolds across the lifespan.

The INIAstress Consortium is made up of researchers across the country who study alcohol abuse and stress interactions in using cross-species and computational modeling approaches.

The INIA Neuroimmune Consortium is a multi-disciplinary, collaborative research consortium investigating immune and inflammatory pathways in the brain to discover new treatments for alcohol use disorder.

The (NADIA) Consortium studies the persistent effects of adolescent alcohol exposure on adults and explores the brain mechanisms that are at the root of these effects ultimately to inform and advance social and health care initiatives.

The 5-site NCANDA-A consortium examines effects of alcohol use on the developing adolescent brain, and examines brain characteristics that predict alcohol use problems. The consortium has developed a core battery, including structural and functional brain scans and cognitive testing, for use at all five sites.

To facilitate alcohol-related research, NIAAA is currently supporting the collection of autopsied human brain tissue from individuals with alcohol use disorder and from controls for distribution to qualified alcohol research investigators. Tissue collection and distribution is provided by the Brain Tissue Resource Center (BTRC), University of Sydney, Australia. The goal of the "brain bank" is to provide human brain tissue for the study of the neuropathology, neurobiology and neurogenetics of chronic alcohol consumption.

About the BTRC

BTRC is located in the Discipline of Pathology, University of Sydney, Australia, and is under the direction of Associate Professor Greg Sutherland. The purpose of the BTRC is to collect, characterize and distribute post-mortem human brain tissue to be used by neuroscience researchers for the study of alcohol-related brain disorders¹.

To facilitate the collection of human brain tissue by the BTRC, a prospective brain donor program, Using Our Brains, has been established. Through this voluntary program, participants agree to donate their brain to the TRC following their death. Potential donors also undergo annual medical and lifestyle evaluations. This enables the TRC to obtain more accurate and detailed descriptions of the medical histories of the brain tissue collected. Visit the Using Our Brains donor program website for additional information.

Human Tissue for Research

Australian researchers have worked with a substantial population of individuals affected by alcohol use disorder who do not also abuse other drugs, constituting a unique resource for investigators studying alcohol's long term effects on the brain. Since 1985, the BTRC at the University of Sydney has been developing a "brain bank," for which the Center is collecting human brain tissue at autopsy from alcohol-related, malnourished and control cases having confirmed clinical and pathological diagnoses. Diagnoses are confirmed by physician interviews, review of hospital medical records, questionnaires to next-of-kin, and from pathology, radiology and neuropsychology reports.

Investigators interested in alcohol research may submit a request for tissue to the BTRC. Brain tissue may be obtained as either fresh-frozen or formalin-fixed samples.

• Fresh-frozen tissue - At autopsy, one hemisphere is cut into ~10 mm coronal slices and regions of interested dissected; prefrontal cortex, anterior and posterior cingulate cortex, caudate putamen, rostral and caudal thalamus, basal forebrain, hippocampus, amygdala, primary visual cortex, cerebellum, midbrain, pons and medulla. All tissue is then frozen and stored at -80 ^oC.
• Formalin-fixed tissue – The contralateral hemisphere is fixed in 15% buffered formalin, embedded in agar, and sliced coronally at 3 mm intervals. Blocks of fixed brain tissue are prepared from superior frontal cortex, cingulate gyrus, parietal cortex, temporal cortex, occipital cortex, hippocampus, amygdala, thalamus and hypothalamus, basal ganglia, mamillary body, pons, medulla, cerebellum (lateral) and cerebellum (vermis). These are embedded in paraffin. All cortical blocks contain substantial amounts of white matter. The remaining tissue is stored in buffered formalin.

Further descriptions of the tissue available to investigators include the age, sex, post-mortem delay, pH of tissue and disease classification. Questions and inquiries concerning the BTRC and the availability of brain tissue may be directed through the BTRC website.

Requests for Human Tissue

Requests for brain samples should be directed to the BTRC Manager, Julia Stevens, at +61 2 8627 1668, julia.stevens@sydney.edu.au, or nswbtrc@sydney.edu.au. 

To receive tissue, investigators must have IRB or ethics approval for the use of human tissue as required by their parent institution. All tissue requests received by the BTRC are reviewed independently by an external Scientific Advisory Board (SAB). The SAB makes the final recommendation to NIAAA and the BTRC for the distribution of tissue.

Following the SAB recommendation and completion of the Material Transfer Agreement, the BTRC will supply to the investigator the requested tissue and appropriate documentation stripped of all personal identifiers. The Principal Investigator and Research Institution will be responsible for costs incurred for processing the samples e.g. consumables, shipping and compliance with U. S. Customs regulations for the importation of human tissue from foreign countries.

Brain tissue that is received from the BTRC is for the exclusive use of the Principal Investigator, and cannot be redistributed to other researchers without authorization from the BTRC. All material remains the property of the BTRC, and any remaining material must be returned on request. All unused tissue must be returned to the BTRC on completion of the research project.

The BTRC requires that the Principal Investigator provide an annual report of all presentations, disclosures, and publications arising from the use of the materials. The Principal Investigator also agrees to acknowledge the contribution of the Brain Tissue Resource Center (BTRC), and the support of the NIH Grant R28 AA12725 (NIAAA) and other funding agencies in all oral and written presentations, disclosures, and publications resulting from the use of the brain tissue.

References

1. Sheedy, D., Garrick, T., et al. 2008. An Australian brain bank: a critical investment with a high return! Cell Tissue Bank, 9, 205-16.

2. Sutherland, G.,Sheedy, D., et al 2016. The NSW Brain Tissue Resource Centre: Banking for alcohol and major neuropsychiatric disorders research. Alcohol, 52, 33-39.

NIAAA Coordinators

Mark Egli, Ph.D., megli@mail.nih.gov
Director, Division of Neurosciences and Behavior

NIAAA Scientific Advisory Board (SAB) Members

Tatiana Foroud, Ph.D.
P. Michael Conneally Professor of Medical and Molecular Genetics
Chancellor's Professor
Director of Hereditary Genomics Division
Indiana University School of Medicine
Indianapolis, IN

Fulton T. Crews, Ph.D.
Professor and Director
Bowles Center for Alcohol Studies
University of North Carolina at Chapel Hill
Chapel Hill, NC 27599

R. Adron Harris, Ph.D.
Professor and Director
Waggoner Center for Alcohol & Addiction Research
University of Texas
Austin, TX 78713

The Medications Development Branch (MDB) plans, stimulates, develops, and supports pharmacotherapy research to AUD. This includes advancing promising medications through the drug development pipeline: identifying lead compounds and optimizing their structure for potency, stability, selectivity/specificity, bioavailability, testing for preclinical efficacy (e.g., alcohol animal models), completing IND requirements (pharmacokinetic evaluations, toxicology, and formulation/manufacturing), supporting phase 1 studies (pharmacokinetic evaluations, pharmacodynamics/target engagement, safety, alcohol interaction, and abuse liability), conducting human laboratory studies and clinical trials, and directing secondary analyses to improve methodology of pharmacotherapy clinical trials for the treatment of AUD. MDB is also committed to research precision medicine to predict favorable responders (both efficacy and safety) to a specific medication, alcohol/psychiatric comorbidity, especially post-traumatic stress disorder, internal and external collaborations to advance the development of medications for AUD, and training programs to assure that adequate numbers of highly competent scientists are engaged in current and future research on medications development.

High priority MDB activities include:

• Developing and testing novel and repurposed medications for the treatment of AUD
• Advancing precision medicine by identifying  subgroups who respond favorably to experimental compounds. This includes developing novel computational analytical approaches using a combination of patient characteristics and biomarkers; discovering new biomarkers is a high priority that includes the integration of “multi-omics” signature profiles involving expression of genes, RNA, proteins, and metabolites; brain endogenous metabolites, electrophysiological variation, individual cell imaging and other biological mechanisms such as hiPSC-based neuronal models
• Developing new pharmacological treatments to treat patients with AUD and psychiatric comorbidity (e.g., post-traumatic stress disorder)
• Stimulating research that develops and evaluates alcohol biosensors for the purpose of objectively measuring real-time alcohol intake
• Developing and implementing a standardized human laboratory paradigms program for screening/testing promising medications
• Promoting the initial evaluation of promising new compounds in human patients via the NIAAA SBIR Investigational New Drug (IND)-enabling program

The Treatment, Health Services, and Recovery Branch (THSRB) stimulates and supports research in broad categories such as health services, behavioral therapies and mechanisms of behavioral change, recovery, translational research, and innovative methods and technologies for AUD treatment and sustaining recovery. Other areas of interest include topics focusing on special-emphasis and underserved populations, including HIH-designated US health disparity populations, as well as those with co-occurring disorders, and fetal alcohol spectrum disorders (FASD). In all studies, at all levels from FASD to elderly, efforts are made to include participants that reflect the diversity of the population at large.  High priority THSRB activities include:

• Improving health services research: focusing on four main areas: 1) make evidence-based treatment more accessible to patients; 2) make treatment settings more appealing to patients; 3) make treatments more affordable; and 4) disseminate and implement evidence-based behavioral and pharmacological treatments into professional healthcare practices. Other areas include:
  • Improving access to evidence-based treatments by identifying and developing strategies to reduce the barriers (personal and structural) that prevent people with AUD and alcohol misuse from seeking and receiving appropriate care
  • Exploring the treatment gap as it relates to sex, age (from adolescence through older adulthood), race/ethnicity, socio-economic status, immigration status, and health literacy, and improving service delivery systems and innovations to facilitate access to care
  • Removing the stigma of AUD and integrate AUD treatment into mainstream health care
• Improving the effectiveness of behavioral interventions:
  • Evaluating evidence-based behavioral therapies in real world treatment settings
  • Disseminating clinical practice findings from mechanism of behavioral change studies that have shown promise in enhancing the effectiveness of behavioral therapies
  • Using dynamic and person-centered statistical modeling approaches to evaluate how heterogeneity impacts alcohol use behavior within specific AUD treatments
• Understanding the dynamics of post-treatment recovery (see NIAAA’s research definition of recovery) :
  • Explore the neurobiological, psychological, environmental, and social factors that influence post-treatment recovery
  • Determine trajectories of recovery in subgroups of people with different cultural and socioeconomic backgrounds, cognitive abilities, and medical histories
  • Identify factors associated with so-called natural recovery and how these factors can be applied to change the behavior of those in treatment
  • Explore continuing care treatments that aim to support long-term recovery   
• Understanding how the social determinants of health (i.e., environmental, social, cultural, and economic factors) influence outcomes and sustainability in health disparities:
  • Removing barriers that keep racial, ethnic, and sex minorities from seeking and receiving appropriate health care
  • Implementing effective treatments that are tailored for these populations in diverse clinical and other settings
  • Determining how social/cultural factors influence treatment accessibility, effectiveness, and long-term recovery
  • Developing measures to assess care delivery models to better address the issues underlying health disparities
• Improving treatments for co-occurring PTSD, anxiety, depression, and AUD:
  • Integrating treatments for co-occurring AUD and mental health conditions to address the heterogeneity that exists among patients
  • Identifying which types of services, service providers, and treatment settings work best for which subgroups
  • Determining how the treatment of one disorder can influence the risks, progression, and outcome for the other disorder
• Harnessing new technology (e.g., mobile, computer, web-based applications, artificial intelligence/machine learning, geo-locations, and robotics) to increase the accessibility and effectiveness of a variety of treatments:
  • Using new technologies to disseminate evidence-based behavioral treatments among hard-to-reach populations, improve effectiveness of telemedicine, and enhance the continuum of care  
  • Investigating new digital technology ways of capturing real-time data in clinical trials and treatment protocols
• Improving clinical research methods:
  • Developing efficient, adaptive clinical trial designs and statistical analyses that allow treatment adjustments based on the changing disease status of the patient
  • Exploring new statistical models and methods for evaluating treatment effectiveness and recovery
  • Investigating statistical approaches that capture changes in outcomes over time and convey results that are more clinically intuitive.
• Improving alcohol treatment outcomes for women:
  • Comparing effectiveness of standard treatment approaches, such as group counseling and relapse prevention, in single-sex vs. mixed-sex groups   
  • Developing new strategies for alcohol screening, diagnosis, and interventions and tailor them to women in diverse settings, including prenatal care and specialty health care 
  • Understanding the impact of coexisting conditions, including other substance use and mental health disorders, on alcohol-related health care, illness, and death among girls and women  
  • Examining the effects of stress, early childhood trauma, childhood adverse events, and co-occurring disorders on women’s drinking  
• Increasing the number of behaviorally-oriented clinical researchers (primarily clinical psychologists) who receive NIAAA training and career development grants (F’s, K’s—especially, the K99/00).

NIAAA-supported research has led to advancements in medications for alcohol use disorder.

The medications development branch supports a well-developed, integrated program called the NIAAA Alcohol Pharmacotherapy Evaluation Program (APEP) to help encourage the development of medications to treat AUD, and to bridge the gap between preclinical studies and Phase III clinical trials. APEP efficiently advances candidate therapeutic compounds by conducting Phase II, human laboratory, and alcohol interaction clinical trials.

NIAAA DTR has developed a formal conceptual and operational definition of recovery for the alcohol treatment and recovery field.