Comorbidity of Alcoholism and Antisocial Personality Disorder
R.O. Pihl McGill University
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.
The Role of Different Motivational Systems
• Motivational system responding to threat • The Cognitive Control System • Motivational system responding to reward
Behavior Aggression
Threatening or punishing behavior
(Behaviorally-linked) Sensory information
Executive Cognitive Functions
Facilitory: Cue for Reward
Inhibitory: Cue for Punishment
Behavior Aggression
Threatening or punishing behavior
(Behaviorally-linked) Sensory information
Inhibits
Executive Cognitive Functions
Facilitory: Cue for Reward
Inhibitory: Cue for Punishment
Acute Alcohol Intoxication
Behavior Aggression
Threatening or punishing behavior
(Behaviorally-linked) Sensory information
Inhibits
Executive Cognitive Functions
Disorganizes
Facilitory: Cue for Reward
Inhibitory: Cue for Punishment
Acute Alcohol Intoxication
Behavior Aggression
Threatening or punishing behavior
(Behaviorally-linked) Sensory information
Inhibits
Executive Cognitive Functions
Disorganizes
Facilitory: Cue for Reward
Inhibitory: Cue for Punishment
Potentiates
Acute Alcohol Intoxication
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)
Family Pedigree
Heart Rate Response to Alcohol Intoxication (Percent Change)
10 12 14 16 0 2 4 6 8
Non-SOMA SOMA
Low-Aggressive High-Aggressive
*
No. of Alcoholic Beverages per year
600
Low-Aggressive High-Aggressive
*
500
400
300
200
100
0
Non-SOMA
SOMA
12
Alcohol-Induced HR Change from Baseline (BPM)
10
NFH F (N = 49) NFH M (N = 99) UFH F (N = 17) UFH M (N = 30) MFH F (N = 20) MFH M (N = 92) ALC M (N = 12)
8
6
4
2
0
0.4 0.3 0.2 0.1 0 -0.1 -0.2 -0.3 -0.4 SP SR Dimensions of the SPSRQ
Z scores on the SPSRQ
Low HR responders High HR responders
0.5 0.4 0.3 0.2 0.1 0 -0.1 -0.2 -0.3 -0.4 -0.5 H/I AS IMP SS Dimensions of the SURPS
Z scores on the SURPS
Low HR responders High HR responders
Zscore (Number of "Risk Taking" Responses)
0.6 0.4 0.2 0.0 -0.2 -0.4 -0.6 Sober Intoxicated
Low Heart Rate Responders
High Heart Rate Responders
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
Positron Emission Tomography
Alcohol Promotes Dopamine Release in the Human Nucleus Accumbens
…and this release is associated to an increased HR response to alcohol
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
Drinks earned following APTD
15
Number of Subjects
10 5 0
Relative number of drinks compared to balanced condition
More Same Less
Alcohol consumption
5 4 3 2 1 0 High Balanced Low Depleted
Drinks
APTD Change in Drinking and Ethanol Cardiac Response
30
20
10
0
-10 -200 -100 0 100 200 300
percent change in earned drinks
r=.-658, p=.006
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
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
0.8
Zscore (Goldberg's Adjective Markers of the Big Five)
Agreeableness Conscientiousness Emotional Stability Extraversion (Surgency) Intellect
*
0.6 0.4 0.2 0.0
* p < 0.05
-0.2 -0.4 -0.6 -0.8
Low Heart Rate Responders to Alcohol Intoxication High Heart Rate Responders to Alcohol Intoxication
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
0.8
Subjective effects of alcohol "The worst that I have ever felt" "The best that I have ever felt"
Zscore (Subjective High Assessment Scale)
0.6
*
0.4
0.2
0.0
-0.2
* p = 0.052
-0.4
Low Heart Rate Responders to Alcohol Intoxication High Heart Rate Responders to Alcohol Intoxication
Apparatus: Taylor Aggression Paradigm (TAP)
TAP - Mean Shock Level Selected
0.6
Zscore (Mean Shock Selected)
0.4 0.2 0.0 -0.2 -0.4 -0.6
Sober Intoxicated
Low HR Responders
High HR Responders
Zscore Total Errors (SCALT & NSCALT &SOP)
2.0 1.8 1.6 1.4 1.2 1.0 0.8 0.6 0.4 0.2 0.0 -0.2 -0.4 -0.6 -0.8 -1.0 -1.2 -1.4
Non-SOMA & Non-Aggressive Non-SOMA & Aggressive SOMA & Non-Aggressive SOMA & Aggressive
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.