1. Alcohol Abuse and Alcoholism
NIAAA
National Institute on
Alcohol Abuse and Alcoholism
1-04

2. NIAAA Perspective on the Role of Neuroimaging in Alcohol Research
Ting-Kai Li, M.D.
Director
National Institute on Alcohol Abuse
and Alcoholism
National Institutes of Health
Department of Health and Human Services
International Conference on Applications of Neuroimaging to Alcoholism
Yale Center for the Translational
Neuroscience of Alcoholism
January 17, 2004

3. In the United States:
14 million Americans suffer from alcohol abuse or dependence – 100,000 die annually
One in four children under age 18 is exposed to family alcohol problems
Between 20%-40% of hospital admissions are alcohol-related
Alcohol problems cost U.S. society an estimated $185 billion annually

4. Disease Burden by Illness - DALY United States, Canada and Western Europe, 2000 15 - 44 year olds2 4 6 8 10 12 14 16 18
Percent of Total
Hearing Loss, adult onset
Alcohol use disorders
HIV/AIDS
Schizophrenia
Migraine
Bipolar disorder
Self inflicted injuries
Drug use disorders
Road traffic accidents
Unipolar
depressive disorders
Source: WHO – Burden of Disease Statistics, 2001

5. NIAAA’s Contemporary Mission
To create a knowledge base that will yield the greatest good for the largest proportion of the population by:
Increasing understanding of normal and abnormal biological functions and behavior relating to alcohol use
Improving the diagnosis, prevention, and treatment of alcohol-related problems and alcoholism
Enhancing the access to quality health care

6. Cumulative Distribution of Alcohol Consumption
Source: Greenfield and Rogers; J. Stud. Alcohol 60:; 79-89, 1999

7. Alcohol Abuse
Alcohol abuse is a pattern of high-risk* drinking that results in several complex outcomes, including:
Personal problems such as illegal underage drinking; drinking-related injuries and death; impact on memory and cognition; loss of employment, family, friends, and other significant relationships; and increased risk for health problems and organ damage…
*High-risk drinking: for Men: more than 14 drinks/week or 5 or more drinks per occasion; for Women: more than 7 drinks/week or 4 or more drinks per occasion (Helping Patients With Alcohol Problems -- A Health Practitioner's Guide, NIAAA, 2003)

8. Alcohol Abuse
…Problems to others, including homicides, sexual assault and other forms of interpersonal crime and violence, property damage, and risk for injury and death
Problems for society, including increased health care costs, loss of economic productivity, and balancing economic, health, and social benefits of alcohol with the significant adverse consequences of high- risk drinking

9. Alcohol Dependence
Alcohol Dependence (Alcoholism) is a common complex disease characterized by a persistent and progressive pattern of abnormally intense alcohol-seeking behavior that, over time, results in the
loss of control over drinking
a preoccupation with drinking
the development of tolerance and dependence

10. Multidisciplinary and Transdisciplinary Research
- animal models to humans
- medications development
Translational Research
Epidemiology
Prevention
Treatment and Recovery
Genetics
Neuroscience
Pharmacokinetics
and Metabolism

11. Alcohol-related health, personal, and social problems arise from drinking:
too much too fast
too much too often

12. Prevalence of Lifetime Alcohol Dependence by Age of First Alcohol Use and Family History of Alcoholism

13. Age at Onset of DSM-IV Alcohol Dependence
Source: NIAAA National Epidemiologic Survey on Alcohol and Related Conditions, 2003

14. Basic Questions in Alcohol Abuse and Dependence
Why people drink
Why some drink more than others
Why some drink despite negative consequences

15. Between Individual Variations in Responses to Alcohol
Pharmacokinetics: absorption, distribution, and metabolism of alcohol
3-4 fold
Pharmacodynamics: subjective and objective responses to alcohol
2-3 fold
Between Individual Variations in Responses to Alcohol

16. Variation in Brain Exposure to Alcohol

18. Ethanol Elimination Rates in Monozygotic (MS) and Dizygotic (DZ) Twins: Evidence for Genetic Influence
Ethanol Elimination Rate (mg/kg/h)
Range (80 subjects)
Mean - ±SD
102 ± 22
Intraclass Correlation Coefficient (r)
for MZ Twins (19 pairs)
0.76
for DZ Twins (21 pairs)
0.28
Heritability
h2=0.5 [MZ+DZ]
0.66

19. Metabolism of Ethanol and Acetaldehyde in Liver Cells

20. acetaldehyde Acetate Ethanol salsolinol? adenosine?
stimulant
depressant
stimulant (CNS)
aversive (systemic)
Addiction:
acetaldehyde
Acetate
Ethanol
salsolinol?
adenosine?

21. Biphasic Properties of Alcohol

22. Physiological Approaches
Molecular Approaches
Physiological Approaches
Genomics
Neuroimaging
Proteomics
Electrophysiology
Metabolomics
Drug self-administration (oral, iv, intracranial)

23. Selectively Bred Alcohol-Preferring Rats as Animal Model to Study Alcoholism
Voluntarily consume 6-8g ethanol/kg/day
Attain BACs of 0.05 – 0.25 g%
Work to obtain the ethanol
Consume ethanol for its pharmacological effects (not taste, smell, or calories)
Develop tolerance with chronic drinking
Develop physical dependence with chronic drinking

25. Alcohol Deprivation Effect
(ADE)
Temporary increase in alcohol consumption following a period of alcohol deprivation
Observed in rats, mice, monkeys, and humans
Animal model for studying relapse

26. Repeated Deprivations – Concurrent EtOH Concentrations

28. Neuroimaging is a Critical Technology for Translational Alcohol Research
Animal models to human populations
Metabolites and receptors to medications development

29. Workshop on International Collaborative Research
Co-sponsored by NIAAA and the German Ministry on Education and Research
Information on funding mechanisms and opportunities
Monday, January 19, Yale TAC Building, auditorium, 1:00 – 4:00 PM

30. Acknowledgement
Brenda G. Hewitt