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 Multiple Characteristics and Genes

COMPLEX GENETIC RISK Myocardial Infarction Type 2 Diabetes Cancer

GENES AND ALCOHOLISM 4 x ↑ Risk for COAs 4 x ↑ Risk for Adopted COAs Higher Risk for ID Twins

RISK FACTORS Alcohol Metabolizing Enzymes Level of Response (LR) Impulsivity Psychiatric Disorders

ALCOHOL METABOLISM Alcohol ADH Acetaldehyde ALDH CO 2 + H 2 O

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

FHalc LR ALCOUTPEER EXPECT COPE PROJECTED

SRE TIME FRAME: DRINKS 1st 5 Recent Heaviest NEEDED TO: Times 3 Mos Feel Effect Feel Dizzy or Slur 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 n Candidates n Association

CANDIDATE GENES Serotonin (5-HTT) K-Channels (KCN) GABA (GABRA6) Dopamine (DRD2/ANKK1)

GENES LR & ALCOHOLISM SerotoninGABA A  6 BOTH LL+ SS+ LL SL SS Pro/Ser Pro/Pro Pro/Ser Pro/Pro LR %ALC

CANDIDATES GABRA6 COMT5HTT GABRG2 DRD2/ANKK1 ADORA GABRA5 DRD4NPY GABRA1 AUTS2EGFR GABRA2 KCNMA1 DGKZ ADH4 CHRNA5 GNASADH1B NMDA PKADH1C CYP2E

KEY FACTORS FH EXPECT LR COPE PEER ALCOUT

FHalc LR ALCOUTPEER EXPECT COPE PROJECTED

THIS LECTURE REVIEWS RISK FOR ALCOHOLOISM SENSITIVITY (LR) AS RISK GENES & ENVIRONMENT RECENT : fMRI & PREVENTION

Mailed Surveys UCSD Undergrads Clinical Interview (SSAGA) Alcohol Challenge fMRI Placebo Scan fMRI Alcohol Scan (High/Low LR subjects matched on demog and substance use)

 120 Subjects  240 fMRI Sessions  480 Sessions

3 COGNITIVE TASKS  Visual Working Memory  Stop Signal  Emotional Faces (Hariri)  All  Near Peak BAC  Different ROIs  LR groups = performance

SAMPLE (N=120) Low LR High LR Age % Female Drink f/mo Drink/Day a # Conduct Probs min BAC

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 STUDY  Questionnaire 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 PREVIDEO 41 MO. FUCHANGE % LOW LR LR Gp Usual Gp HIGH LR LR Gp Usual Gp

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 Multiple Characteristics and Genes

RISK FACTORS Alcohol Metabolizing Enzymes Level of Response (LR) Impulsivity Psychiatric Disorders

SRE TIME FRAME: DRINKS 1st 5 Recent Heaviest NEEDED TO: Times 3 Mos Feel Effect Feel Dizzy or Slur Speech Stumble Fall Asleep

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

LR IS:  Genes and Environment  Observed Early  Predicts Dx

FHalc LR ALCOUTPEER 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