Transcript Figure 1 - Mean group differences (+ SE) between Low (n

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
(Behaviorally-linked)
Sensory information
Aggression
Threatening or punishing
behavior
Executive Cognitive Functions
Facilitory:
Cue for Reward
Inhibitory:
Cue for Punishment
Behavior
(Behaviorally-linked)
Sensory information
Aggression
Inhibits
Threatening or punishing
behavior
Executive Cognitive Functions
Facilitory:
Cue for Reward
Inhibitory:
Cue for Punishment
Acute
Alcohol
Intoxication
Behavior
(Behaviorally-linked)
Sensory information
Aggression
Inhibits
Threatening or punishing
behavior
Executive Cognitive Functions
Facilitory:
Cue for Reward
Disorganizes
Inhibitory:
Cue for Punishment
Acute
Alcohol
Intoxication
Behavior
(Behaviorally-linked)
Sensory information
Aggression
Inhibits
Threatening or punishing
behavior
Executive Cognitive Functions
Facilitory:
Cue for Reward
Disorganizes
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)
16
Low-Aggressive
High-Aggressive
Non-SOMA
*
14
12
10
8
6
4
2
0
SOMA
No. of Alcoholic Beverages per year
600
Low-Aggressive
High-Aggressive
*
500
400
300
200
100
0
Non-SOMA
SOMA
Alcohol-Induced HR Change from Baseline (BPM)
12
10
8
6
4
2
0
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)
Z scores on the SPSRQ
0.4
0.3
0.2
0.1
0
-0.1
-0.2
-0.3
-0.4
Low HR responders
High HR responders
SP
SR
Dimensions of the SPSRQ
Z scores on the SURPS
0.5
0.4
0.3
0.2
0.1
0
-0.1
-0.2
-0.3
-0.4
-0.5
Low HR responders
High HR responders
H/I
AS
IMP
Dimensions of the SURPS
SS
Zscore (Number of "Risk Taking" Responses)
0.6
0.4
Sober
Intoxicated
0.2
0.0
-0.2
-0.4
-0.6
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
Number of Subjects
15
10
More
Same
Less
5
0
Relative number of drinks compared to balanced
condition
Drinks
Alcohol consumption
5
4
3
2
1
0
High
Low
Balanced
Depleted
APTD Change in Drinking and Ethanol Cardiac Response
30
20
10
0
-10
-200
-100
0
percent change in earned drinks
r=.-658, p=.006
100
200
300
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
Zscore (Goldberg's Adjective Markers of the Big Five)
0.8
0.6
Agreeableness
Conscientiousness
Emotional Stability
Extraversion (Surgency)
Intellect
*
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
Zscore (Subjective High Assessment Scale)
0.8
Subjective effects of alcohol
"The worst that I have ever felt"
"The best that I have ever felt"
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
Zscore (Mean Shock Selected)
0.6
0.4
Sober
Intoxicated
0.2
0.0
-0.2
-0.4
-0.6
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.