Post on 31-Dec-2015
transcript
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 punishingbehavior
(Behaviorally-linked)
Sensory information
Executive Cognitive Functions
Facilitory:Cue for Reward
Inhibitory:Cue for Punishment
Behavior
Aggression
Threatening or punishingbehavior
Acute Alcohol
Intoxication
(Behaviorally-linked)
Sensory information
Executive Cognitive Functions
Facilitory:Cue for Reward
Inhibitory:Cue for Punishment
Inhibits
Behavior
Aggression
Threatening or punishingbehavior
Disorganizes
Acute Alcohol
Intoxication
(Behaviorally-linked)
Sensory information
Executive Cognitive Functions
Facilitory:Cue for Reward
Inhibitory:Cue for Punishment
Inhibits
Behavior
Aggression
Threatening or punishingbehavior
Disorganizes
Acute Alcohol
Intoxication
(Behaviorally-linked)
Sensory information
Potentiates
Executive Cognitive Functions
Facilitory:Cue for Reward
Inhibitory:Cue for Punishment
Inhibits
The Role of Different Motivational Systems
• Environmental triggers1. Threat, anxiety (novelty, cues of punishment, etc…)
2. Monotony (lack of immediate reinforcement)
• Genetically influenced susceptibility1. Anxiety
2. Boredom
• Desired alcohol reinforcement1. Anxiolysis (serotonin & GABA effects)
2. Stimulation (Dopaminergic effects)
0
2
4
6
8
10
12
14
16*
Non-SOMAHea
rt R
ate
Res
pons
e to
Alc
ohol
Into
xica
tion
(Per
cent
Cha
nge)
SOMA
Low-Aggressive High-Aggressive
0
100
200
300
400
500
600
*
Non-SOMA
No.
of A
lcoh
olic
Bev
era
ges
per
year
SOMA
Low-Aggressive High-Aggressive
0
2
4
6
8
10
12
Alc
ohol
-Ind
uced
HR
Cha
nge
from
Bas
elin
e (B
PM
) 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)
Alcohol Induced Changes in BAES Stimulation
-30
-20
-10
0
10
20
30
40
50
pre-alcohol 30min 40min 60min 90min 120min 150min
HHRR
LHRR
-0.4-0.3-0.2-0.1
00.10.20.30.4
SP SR
Dimensions of the SPSRQ
Z s
core
s on
the
SPSR
Q Low HR responders
High HR responders
-0.5
-0.4-0.3
-0.2-0.1
0
0.10.2
0.30.4
0.5
H/I AS IMP SS
Dimensions of the SURPS
Z s
co
res o
n t
he S
UR
PS
Low HR responders
High HR responders
-0.6
-0.4
-0.2
0.0
0.2
0.4
0.6
High Heart RateResponders
Low Heart RateRespondersZ
scor
e (N
umbe
r of
"R
isk
Tak
ing"
Res
pons
es)
Sober Intoxicated
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
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
0
5
10
15
Relative number of drinks compared to balanced condition
Nu
mb
er o
f S
ub
ject
s
MoreSameLess
APTD Change in Drinking and Ethanol Cardiac ResponseAPTD Change in Drinking and Ethanol Cardiac Response
r=.-658, p=.006r=.-658, p=.006
percent change in earned drinks
3002001000-100-200
pe
rce
nt
ch
an
ge
in
he
art
ra
te
30
20
10
0
-10
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
-0.8
-0.6
-0.4
-0.2
0.0
0.2
0.4
0.6
0.8
* p < 0.03
* **
** p < 0.02
**
Low Heart Rate Respondersto Alcohol Intoxication
High Heart Rate Respondersto Alcohol Intoxication
Zsc
ore
(Ave
rage
of 1
988
to 1
995
long
itudi
nal s
core
s) Physical Aggression Destruction of Property Theft
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
-0.6
-0.4
-0.2
0.0
0.2
0.4
0.6
0.8
* p < 0.05
*
High Heart Rate Respondersto Alcohol Intoxication
Low Heart Rate Respondersto Alcohol Intoxication
Zsc
ore
(Gol
dber
g's
Adj
ectiv
e M
arke
rs o
f the
Big
Fiv
e)
Agreeableness Conscientiousness Emotional Stability Extraversion (Surgency) Intellect
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
-0.4
-0.2
0.0
0.2
0.4
0.6
0.8
*
* p = 0.052
High Heart Rate Respondersto Alcohol Intoxication
Low Heart Rate Respondersto Alcohol Intoxication
Zsc
ore
(Sub
ject
ive
Hig
h A
sses
smen
t Sca
le)
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
0.4
0.6
High HR RespondersLow HR Responders
Zsc
ore
(M
ea
n S
ho
ck S
ele
cte
d) Sober
Intoxicated
TAP - Mean Shock Level Selected
-1.4-1.2-1.0-0.8-0.6-0.4-0.20.00.20.40.60.81.01.21.41.61.82.0
Zsc
ore
Tot
al E
rror
s (S
CA
LT &
NS
CA
LT &
SO
P)
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.