Post on 19-Jun-2015
description
Mul$ple Pathways to Addic$ons
Bob Pihl McGill University
Why the need to determine differen$al pathways?
The Epidemiology and Consequences of Alcohol Abuse
• Life$me Prevalence 10.3 – 23% Male=13.8, female= 7.1 Na$ve American= 18.4
• Peak age late teens early twen$es
• Highly co morbid mood, anxiety and personality disorders
• 3rd most prevalent health problem
• A cause in 1/3 of general hospital admissions
• Primary cause of emergency room admissions
• Involved in 39% of traffic accidents , 50% of violent interac$ons.
Treatment & Preven$on
• % treated in ones life$me.
• 8% Abuse • 38% Dependence • Deference is given to trea$ng co morbid disorders.
• Relapse is the rule.
• Generalized preven$on programs can increase drug use.
• More than 40% of those who begin drinking before age 15 become dependent, versus 10% a_er21.
7
Advantages of High Risk Research
• Contemporaneous recording of events • Allows study of “escape” from risk process • Allows the study of the heterogeneity of abnormal outcomes • Allows for subdivision in terms of age of onset • Allows for assessment of changes over $me within individuals • Can some$mes elucidate feedback mechanisms, circular
processes and chain of events typically important in causa$on
Some At Risk Groups
• Family History • Par$cular Personality Traits.
• ADHD, CD, ASPD. • Anxiety/ Depressive Disorders
• Early Alcohol Use • Biological Varia$ons
• Certain Occupa$ons • Premature Adolescence
• School Failure • Peer Rela$onships • Family Status • Bureaucra$c Induced Disorders
Date of download: 3/21/2013" Copyright © 2012 American Medical Association. All rights reserved."
From: Mapping Common Psychiatric Disorders: Structure and Predictive Validity in the National Epidemiologic Survey on Alcohol and Related Conditions"
JAMA Psychiatry. 2013;70(2):199-207. doi:10.1001/jamapsychiatry.2013.281"
Figure. Three-dimensional representation of the space among psychiatric disorders. Each disorder is represented in the color of the factor for which it has higher loadings. Although the factors are correlated (see Table 1 and the “Results” section), they are represented as orthogonal to facilitate visualization. 1 indicates alcohol abuse; 2, alcohol dependence; 3, drug abuse; 4, drug dependence; 5, nicotine dependence; 6, major depressive disorder; 7, bipolar disorder; 8, dysthymia; 9, panic disorder; 10, social anxiety disorder; 11, specific phobia; 12, generalized anxiety disorder; 13, pathological gambling; 14, avoidant personality disorder; 15, dependent personality disorder; 16, obsessive compulsive personality disorder; 17, paranoid personality disorder; 18, schizoid personality disorder; 19, histrionic personality disorder; 20, antisocial personality disorder."
Figure Legend:"
Moms who drink a lot • NLSCY study
– Over Canadian 10000 families
12
13
14
15
Bureaucra(c Induced Disorders
Immature
Problems
Labeled
900,000 ADHD’s misdiagnosed and treated in the US. ( Elder, 2010, Journal of Health Economics)
Family Pedigree
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Assump$ons & Strategy
• There are mul$ple and o_en discrete e$ologies.
• A high risk approach is required. • How an individual responds to the drug should differen$ate suscep$bility. Hence procedurally an alcohol challenge is preferable.
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Alcohol Challenge – Basic Design
Subject Selec(on
Pre-‐tes(ng/ Control
Manipula(on
Alcohol/ Placebo Challenge
Post-‐tes(ng Manipula(o
n
Dampening
Drinking to Cope & Brain Response to Emo$onal Faces
Amygdalar Response to Dis(nct Facial Expressions in Anxiety-‐Sensi(ve Subjects
M-‐AS VS F-‐AS
AG HC Putamen Caudate NAc mFOG
-1.0
-0.8
-0.6
-0.4
-0.2
0.0
BO
LD S
igna
l Int
ensi
ty (a
.u.)
Brain Region
Alcohol Placebo
AG HC Putamen Caudate NAc lOFG
-0.6
-0.4
-0.2
0.0
0.2
BO
LD S
igna
l Int
ensi
ty (a
.u.)
Brain Region
Alcohol Placebo
S$mula$on
-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 IntoxicationZs
core
(Ave
rage
of 1
988
to 1
995
long
itudi
nal s
core
s)
Physical Aggression Destruction of Property Theft
-0.6
-0.4
-0.2
0.0
0.2
0.4
0.6
High HR RespondersLow HR Responders
Zsco
re (M
ean
Sho
ck S
elec
ted)
Sober Intoxicated
Aggressive Behavior and the High Heart Rate Response
age 10 to 17 delinquency scores TAP - Mean Shock Level Selected
A. High & B. Low nega$ve effects of alcohol
a
t"
3.1"
5.7"
b
t"
-3.1"
-7.2"
Alcohol Self-Administration
Barrett et al, 2005
-10
0
10
20
30
Etha
nol-I
nduc
ed ∆ H
eart
Rate
-1 -0.5 0 0.5 1 1.5∆ Alcohol Self-Administration
(log PR breakpoint)
r = 0.713, p ≤ 0.002
0
0.5
1
1.5
2
2.5
3
Prog
ress
ive
Ratio
Bre
akpo
int (
log)
High HR Low HR
APTD+DOPA
APTD
BAL
***
Subjects with a High Heart rate Response to Alcohol Challenge
• Self-‐rate more of a posi$ve response • Drink more • Remember more words learned before drinking
• Increase plasma endorphin levels • The heart rate response is blocked by neltrexone
• It can be reduced via condi$oning.
-0.4-0.3-0.2-0.1
00.10.20.30.4
SP SR
Dimensions of the SPSRQ
Z s
co
res o
n t
he S
PS
RQ Low HR responders
High HR responders
Alcohol Induced Changes in BAES Stimulation
-‐30
-‐20
-‐10
0
10
20
30
40
50
pre-‐alcohol 30min 40min 60min 90min 120min 150min
HHR RLHR R
The High Heart Rate Response and the Subjec$ve High
-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
Zsco
re (S
ubje
ctiv
e H
igh
Ass
essm
ent S
cale
) Subjective effects of alcohol "The worst that I have ever felt" "The best that I have ever felt"
Subjective High Assessment Scale Subjective High across the blood alcohol curve
34
-0.4-0.3-0.2-0.1
00.10.20.30.4
SP SR
Dimensions of the SPSRQ
Z sc
ores
on
the
SPSR
Q Low HR respondersHigh HR responders
Alcohol-Induced HR Change as a Function of HR Group and Drinking Condition (Reward/Non-Reward)
02
46
810
1214
Low HRresponders
High HRresponders
HR response to alcohol intoxication groups
HR
in
cre
ase
in
BP
M
HR day 1HR day 2 n-rHR day 2 r
Design
• N= 56 males
• Day I
– Alcohol challenge
– Subjects divided (medium split) into High and Low HR response
• Day II
– While sober, participated in a task where auditory and visual cues were paired With reward or no reward
– Subjects then randomly assigned and alcohol challenged and were exposed to conditioned cues.
-0.5-0.4-0.3-0.2-0.1
00.10.20.30.40.5
H/I AS IMP SS
Dimensions of the SURPS
Z sc
ores
on
the
SURP
S Low HR respondersHigh HR responders
38
39
0
10
20
30
40
50
60
EducationalFilm
MotivationMisMatched
MotivationMatched
Rat
e of
Rem
issi
on(%
of w
omen
no
long
er m
eetin
g cr
iteria
for s
ubst
ance
abu
se o
r dep
ende
nce)
Brief Intervention
Date of download: 3/21/2013" Copyright © 2012 American Medical Association. All rights reserved."
From: Effectiveness of a Selective, Personality-Targeted Prevention Program for Adolescent Alcohol Use and Misuse: A Cluster Randomized Controlled Trial"
JAMA Psychiatry. 2013;70(3):334-342. doi:10.1001/jamapsychiatry.2013.651"
Figure 4. Estimated probability of reporting problem drinking symptoms × severity of problem drinking symptoms in high-risk (HR) and low-risk (LR) youth attending intervention and control schools. T2 indicates 6 months after intervention; T3,12 months after intervention; T4,18 months after intervention; and T5, 24 months after intervention."
Figure Legend:"
General Ques$ons
• The long term interven$on effect for the different risk groups.
• The neuropsychological/cogni$ve correlates of each risk group, the effect of substance use and non/limited use.
• The brain correlates of risk for each group, the effect of the interven$on and the effect of substance use and abuse.
Inner Peace ��� If you can start the day without caffeine, If you can always be cheerful, ignoring aches and pains, If you can resist complaining and boring people with your troubles, If you can eat the same food every day and be grateful for it, If you can understand when your loved ones are too busy to give you any $me, If you can take cri$cism and blame without resentment, If you can conquer tension without medical help, If you can relax without alcohol, If you can sleep without the aid of drugs,
A DOG