THIS LECTURE REVIEWS RISK FOR ALCOHOLISM SENSITIVITY (LR) AS RISK GENES & ENVIRONMENT RECENT...
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Transcript of THIS LECTURE REVIEWS RISK FOR ALCOHOLISM SENSITIVITY (LR) AS RISK GENES & ENVIRONMENT RECENT...
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
