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THIS LECTURE REVIEWS
RISK FOR ALCOHOLISM
SENSITIVITY (LR) AS RISK
GENES & ENVIRONMENT
RECENT DEVELOPMENTS
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THIS LECTURE REVIEWS
RISK FOR ALCOHOLISM
SENSITIVITY (LR) AS RISK
GENES & ENVIRONMENT
RECENT DEVELOPMENTS
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ALCOHOLISM RISK
Environment40%
Genetics60%
Multiple Characteristics and Genes
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COMPLEX GENETIC RISK
Myocardial Infarction
Type 2 Diabetes
Cancer
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RISK FACTORS
Alcohol Metabolizing Enzymes
Level of Response (LR)
Impulsivity
Psychiatric Disorders
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ALCOHOL METABOLISM
Alcohol ADH Acetaldehyde
ALDH
CO2 + H2O
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THIS LECTURE REVIEWS
RISK FOR ALCOHOLISM
SENSITIVITY (LR) AS RISK
GENES & ENVIRONMENT
RECENT DEVELOPMENTS
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LR RATIONALE Youth Drink for Effects
If Need More, Drink More
Then Heavy Drinking Affects
Peers
Expectations
Stress
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0
20
40
60
80
100
120
140
0 30 60 90 120 150 180
Time
Effe
ct
FHNFHP.05
.01
.05.05
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SRESRE TIME FRAME:
DRINKS 1st 5 Recent
HeaviestNEEDED TO: Times 3 Mos
Feel Effect
Feel Dizzy orSlur Speech
Stumble
Fall Asleep
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LR IS GENETIC
1° Relatives .20
Unrelated .02
Twin Heritability 60%
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LR PREDICTS OUTCOME
San Diego Study
Australian Twins
Danish Adoptees
Colorado Twins
COGA Kids
ALSPAC Kids
Pittsburgh Study
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LR IS: Genes and Environment
Observed Early
Predicts Diagnosis
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THIS LECTURE REVIEWS
RISK FOR ALCOHOLOISM
SENSITIVITY (LR) AS RISK
GENES & ENVIRONMENT
RECENT DEVELOPMENTS
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GENES FOR LR
Animal Models CandidatesAssociation
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CANDIDATE GENESSerotonin (5-HTT)
K-Channels (KCN)
GABA (GABRA6)
Dopamine (DRD2/ANKK1)
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CANDIDATESGABRA6 COMT 5HTT
GABRG2 DRD2/ANKK1 ADORA
GABRA5 DRD4 NPY
GABRA1 AUTS2 EGFR
GABRA2
KCNMA1 DGKZ ADH4
CHRNA5 GNAS ADH1B
NMDA PK ADH1C
CYP2E
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KEY FACTORS
FH EXPECT
LR COPE
PEER ALCOUT
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FHalc
LR
ALCOUT
PEER EXPECT
COPE
PROJECTED
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THIS LECTURE REVIEWS
RISK FOR ALCOHOLOISM
SENSITIVITY (LR) AS RISK
GENES & ENVIRONMENT
RECENT : fMRI & PREVENTION
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120 Subjects
240 fMRI Sessions
480 Sessions
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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
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KEY FINDINGS fMRI Relates to LR
Low LR and High LR Differ Placebo
Alcohol
Interactions
Implications
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PREVENTION
Teach About Risk
Prevent Based on Risk
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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
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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
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PREVENTION:
Develop for Specific Risk
Evaluate in Subgroups
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THIS LECTURE REVIEWED
RISK FOR ALCOHOLISM
SENSITIVITY (LR) AS RISK
GENES & ENVIRONMENT
RECENT DEVELOPMENTS
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GENES AND ALCOHOLISM
4 x ↑ Risk for COAs
4 x ↑ Risk for Adopted COAs
Higher Risk for ID Twins
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ALCOHOLISM RISK
Environment40%
Genetics60%
Multiple Characteristics and Genes
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RISK FACTORS
Alcohol Metabolizing Enzymes
Level of Response (LR)
Impulsivity
Psychiatric Disorders
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SRESRE TIME FRAME:
DRINKS 1st 5 Recent
HeaviestNEEDED TO: Times 3 Mos
Feel Effect
Feel Dizzy orSlur Speech
Stumble
Fall Asleep
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0
20
40
60
80
100
120
140
0 30 60 90 120 150 180
Time
Effe
ct
FHNFHP.05
.01
.05.05
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LR RATIONALE Youth Drink for Effects If Need More, Drink More Then Heavy Drinking Affects
PeersExpectationsStress
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LR IS: Genes and Environment
Observed Early
Predicts Dx
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FHalc
LR
ALCOUT
PEER EXPECT
COPE
PROJECTED
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BRAIN MECHANISMS Images relate to LR
Low LR differ from high LR Placebo
Alcohol
Interactions
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PREVENTION
Teach About Risk
Prevent Based on Risk
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