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

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

5. ALCOHOLISM RISK Multiple Characteristics and Genes

6. COMPLEX GENETIC RISK Myocardial Infarction Type 2 Diabetes Cancer

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

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

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

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

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

12. FHalc LR ALCOUTPEER EXPECT COPE PROJECTED

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

15. LR IS GENETIC 1° Relatives.20 Unrelated.02 Twin Heritability 60%

16. LR PREDICTS OUTCOME San Diego Study Australian Twins Danish Adoptees Colorado Twins COGA Kids ALSPAC Kids Pittsburgh Study

17. LR IS:  Genes and Environment  Observed Early  Predicts Diagnosis

18. THIS LECTURE REVIEWS RISK FOR ALCOHOLOISM SENSITIVITY (LR) AS RISK GENES & ENVIRONMENT RECENT DEVELOPMENTS

20. GENES FOR LR Animal Models n Candidates n Association

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

22. GENES LR & ALCOHOLISM SerotoninGABA A  6 BOTH LL+ SS+ LL SL SS Pro/Ser Pro/Pro Pro/Ser Pro/Pro LR %ALC -.89 -.30 00 57 21 12 -1.01 -.27 71 23 -1.29 +.03 100 00

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

25. KEY FACTORS FH EXPECT LR COPE PEER ALCOUT

26. FHalc LR ALCOUTPEER EXPECT COPE PROJECTED

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

29. 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)

30.  120 Subjects  240 fMRI Sessions  480 Sessions

31. 3 COGNITIVE TASKS  Visual Working Memory  Stop Signal  Emotional Faces (Hariri)  All  Near Peak BAC  Different ROIs  LR groups = performance

32. SAMPLE (N=120) Low LR High LR Age19.8 20.1 % Female52.652.6 Drink f/mo4.5 3.5 Drink/Day a 4.1 3.3 # Conduct Probs 0.41 0.31 60 min BAC0.06 0.06

36. KEY FINDINGS  fMRI Relates to LR  Low LR and High LR Differ  Placebo  Alcohol  Interactions  Implications

38. PREVENTION Teach About Risk Prevent Based on Risk

39. 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

40. USUAL DRINKS ACROSS TIME PREVIDEO 41 MO. FUCHANGE % LOW LR LR Gp 5.03.73.0-40 Usual Gp 5.24.44.3-17 HIGH LR LR Gp 5.13.23.4-33 Usual Gp 4.92.92.2-55

41. PREVENTION: Develop for Specific Risk Evaluate in Subgroups

42. THIS LECTURE REVIEWED RISK FOR ALCOHOLISM SENSITIVITY (LR) AS RISK GENES & ENVIRONMENT RECENT DEVELOPMENTS

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

45. ALCOHOLISM RISK Multiple Characteristics and Genes

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

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

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

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

51. FHalc LR ALCOUTPEER EXPECT COPE PROJECTED

52. BRAIN MECHANISMS  Images relate to LR  Low LR differ from high LR  Placebo  Alcohol  Interactions

53. PREVENTION Teach About Risk Prevent Based on Risk