1. Comorbidity of Alcoholism and Antisocial Personality Disorder R.O. Pihl McGill University

2. Alcoholism & ASPD Lets avoid the definitional quagmire. Lets agree there is a significant correlation between Alcoholism and ASPD. Lets agree that the nature of the relationship is well understood.

6. The Role of Different Motivational Systems Motivational system responding to threat The Cognitive Control System Motivational system responding to reward

7. Behavior Aggression Threatening or punishing behavior (Behaviorally-linked) Sensory information Executive Cognitive Functions Facilitory: Cue for Reward Inhibitory: Cue for Punishment

8. Behavior Aggression Threatening or punishing behavior Acute Alcohol Intoxication (Behaviorally-linked) Sensory information Executive Cognitive Functions Facilitory: Cue for Reward Inhibitory: Cue for Punishment Inhibits

9. Behavior Aggression Threatening or punishing behavior Disorganizes Acute Alcohol Intoxication (Behaviorally-linked) Sensory information Executive Cognitive Functions Facilitory: Cue for Reward Inhibitory: Cue for Punishment Inhibits

10. Behavior Aggression Threatening or punishing behavior Disorganizes Acute Alcohol Intoxication (Behaviorally-linked) Sensory information Potentiates Executive Cognitive Functions Facilitory: Cue for Reward Inhibitory: Cue for Punishment Inhibits

11. The Role of Different Motivational Systems Environmental triggers 1.Threat, anxiety (novelty, cues of punishment, etc…) 2.Monotony (lack of immediate reinforcement) Genetically influenced susceptibility 1.Anxiety 2.Boredom Desired alcohol reinforcement 1.Anxiolysis (serotonin & GABA effects) 2.Stimulation (Dopaminergic effects)

16. Family Pedigree

25. Subjects with a High Heart rate Response to Alcohol Challenge Self-rate more of a positive response Drink more Remember more words learned before drinking Release more dopamine in the Ventral Striatum

26. Positron Emission Tomography

27. Alcohol Promotes Dopamine Release in the Human Nucleus Accumbens …and this release is associated to an increased HR response to alcohol

29. Background Phenylalanine and tyrosine, two amino acids (AA)found in dietary protein, are the essential building blocks for the production of dopamine in the brain. Ingesting an AA mixture deficient in P&T reduces DA production by 1)causes protein synthesis diminishing the body’s stores of these AA 2) increasing competition of other AAs for transport across the blood brain barrier. Peek effect of depletion occur 4-5 hours following the ingestion of the AA mixture

32. APTD Change in Drinking and Ethanol Cardiac Response r=.-658, p=.006

34. Figure 1 - Mean group differences (+ SE) between Low (n = 19) and High (n = 19) Heart Rate Responders in the average of age 10 to 17 delinquency scores

35. Figure 2 - Mean group differences (+ SE) between Low (n = 18) and High (n = 20) Heart Rate Responders in Goldberg's Adjective Markers of the Big Five assessed at age 19

36. Figure 3 - Mean group differences (+ SE) between Low (n = 20) and High (n = 22) Heart Rate Responders in Subjective High Assessment Scale (SHAS) at age 19

37. Apparatus: Taylor Aggression Paradigm (TAP)

38. TAP - Mean Shock Level Selected

44. Commonalities Alcoholism & ASPD Unusual high heart rate response to high dose of alcohol. High activation of the Cue for Reward System. A system that is dopamine mediated. Reduced ECF functioning.