THIS LECTURE REVIEWS

RISK FOR ALCOHOLISM

SENSITIVITY (LR) AS RISK

GENES & ENVIRONMENT

RECENT DEVELOPMENTS

THIS LECTURE REVIEWS

RISK FOR ALCOHOLISM

SENSITIVITY (LR) AS RISK

GENES & ENVIRONMENT

RECENT DEVELOPMENTS

ALCOHOLISM RISK

Environment40%

Genetics60%

Multiple Characteristics and Genes

COMPLEX GENETIC RISK

Myocardial Infarction

Type 2 Diabetes

Cancer

RISK FACTORS

Alcohol Metabolizing Enzymes

Level of Response (LR)

Impulsivity

Psychiatric Disorders

ALCOHOL METABOLISM

Alcohol ADH Acetaldehyde

ALDH

CO2 + H2O

THIS LECTURE REVIEWS

RISK FOR ALCOHOLISM

SENSITIVITY (LR) AS RISK

GENES & ENVIRONMENT

RECENT DEVELOPMENTS

LR RATIONALE Youth Drink for Effects

If Need More, Drink More

Then Heavy Drinking Affects

Peers

Expectations

Stress

0

20

40

60

80

100

120

140

0 30 60 90 120 150 180

Time

Effe

ct

FHNFHP.05

.01

.05.05

SRESRE TIME FRAME:

DRINKS 1st 5 Recent

HeaviestNEEDED TO: Times 3 Mos

Feel Effect

Feel Dizzy orSlur Speech

Stumble

Fall Asleep

LR IS GENETIC

1° Relatives .20

Unrelated .02

Twin Heritability 60%

LR PREDICTS OUTCOME

San Diego Study

Australian Twins

Danish Adoptees

Colorado Twins

COGA Kids

ALSPAC Kids

Pittsburgh Study

LR IS: Genes and Environment

Observed Early

Predicts Diagnosis

THIS LECTURE REVIEWS

RISK FOR ALCOHOLOISM

SENSITIVITY (LR) AS RISK

GENES & ENVIRONMENT

RECENT DEVELOPMENTS

GENES FOR LR

Animal Models CandidatesAssociation

CANDIDATE GENESSerotonin (5-HTT)

K-Channels (KCN)

GABA (GABRA6)

Dopamine (DRD2/ANKK1)

CANDIDATESGABRA6 COMT 5HTT

GABRG2 DRD2/ANKK1 ADORA

GABRA5 DRD4 NPY

GABRA1 AUTS2 EGFR

GABRA2

KCNMA1 DGKZ ADH4

CHRNA5 GNAS ADH1B

NMDA PK ADH1C

CYP2E

KEY FACTORS

FH EXPECT

LR COPE

PEER ALCOUT

FHalc

LR

ALCOUT

PEER EXPECT

COPE

PROJECTED

THIS LECTURE REVIEWS

RISK FOR ALCOHOLOISM

SENSITIVITY (LR) AS RISK

GENES & ENVIRONMENT

RECENT : fMRI & PREVENTION

120 Subjects

240 fMRI Sessions

480 Sessions

SAMPLE (N=120)Low LR High LR

Age 19.8 20.1

% Female 52.6 52.6

Drink f/mo 4.5 3.5

Drink/Daya 4.1 3.3

# Conduct Probs 0.41 0.31

60 min BAC 0.06 0.06

KEY FINDINGS fMRI Relates to LR

Low LR and High LR Differ Placebo

Alcohol

Interactions

Implications

PREVENTION

Teach About Risk

Prevent Based on Risk

THE STUDYQuestionnaire To Students

~70% Response

Select Matched Low and High LR

Two Prevention Groups LR-Based

State of the Art

Four 45-min Internet Sessions Each

USUAL DRINKS ACROSS TIME

PRE VIDEO 4 1 MO. FU CHANGE %LOW LR

LR Gp 5.0 3.7 3.0 -40

Usual Gp 5.2 4.4 4.3 -17

HIGH LR

LR Gp 5.1 3.2 3.4 -33

Usual Gp 4.9 2.9 2.2 -55

PREVENTION:

Develop for Specific Risk

Evaluate in Subgroups

THIS LECTURE REVIEWED

RISK FOR ALCOHOLISM

SENSITIVITY (LR) AS RISK

GENES & ENVIRONMENT

RECENT DEVELOPMENTS

GENES AND ALCOHOLISM

4 x ↑ Risk for COAs

4 x ↑ Risk for Adopted COAs

Higher Risk for ID Twins

ALCOHOLISM RISK

Environment40%

Genetics60%

Multiple Characteristics and Genes

RISK FACTORS

Alcohol Metabolizing Enzymes

Level of Response (LR)

Impulsivity

Psychiatric Disorders

SRESRE TIME FRAME:

DRINKS 1st 5 Recent

HeaviestNEEDED TO: Times 3 Mos

Feel Effect

Feel Dizzy orSlur Speech

Stumble

Fall Asleep

0

20

40

60

80

100

120

140

0 30 60 90 120 150 180

Time

Effe

ct

FHNFHP.05

.01

.05.05

LR RATIONALE Youth Drink for Effects If Need More, Drink More Then Heavy Drinking Affects

PeersExpectationsStress

LR IS: Genes and Environment

Observed Early

Predicts Dx

FHalc

LR

ALCOUT

PEER EXPECT

COPE

PROJECTED

BRAIN MECHANISMS Images relate to LR

Low LR differ from high LR Placebo

Alcohol

Interactions

PREVENTION

Teach About Risk

Prevent Based on Risk