This is a presentation that was given at the Lost in Translation 2013: Exploring the Origins of Addiction conference that took place on March 25 - 26, 2013 in Vancouver, British Columbia, Canada

1. Mul$ple
Pathways
to
Addic$ons
Bob
Pihl
McGill
University

4. Why
the
need
to
determine
differen$al
pathways?

5. The
Epidemiology
and
Consequences
of
Alcohol
Abuse
•
Life$me
Prevalence
• 3rd
most
prevalent
10.3
–
23%
Male=13.8,
health
problem
female=
7.1
Na$ve
•
A
cause
in
1/3
of
American=
18.4
general
hospital
•
Peak
age
late
teens
admissions
early
twen$es
• Primary
cause
of
• Highly
co
morbid
emergency
room
mood,
anxiety
and
admissions
personality
disorders
•
Involved
in
39%
of
traffic
accidents
,
50%
of
violent
interac$ons.

6. Treatment
&
Preven$on
•
%
treated
in
ones
•
Generalized
preven$on
life$me.
programs
can
increase
•
8%
Abuse
drug
use.
•
38%
Dependence
•
More
than
40%
of
•
Deference
is
given
to
those
who
begin
drinking
before
age
15
trea$ng
co
morbid
disorders.
become
dependent,
versus
10%
a_er21.
•
Relapse
is
the
rule.

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
7

8. Some
At
Risk
Groups
•
Family
History
•
Certain
Occupa$ons
•
Par$cular
Personality
•
Premature
Traits.
Adolescence
•
ADHD,
CD,
ASPD.
•
School
Failure
•
Anxiety/
Depressive
•
Peer
Rela$onships
Disorders
•
Family
Status
• Early
Alcohol
Use
•
Bureaucra$c
Induced
• Biological
Varia$ons
Disorders

10. 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 Legend:"
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;
Copyright © 2012 American Medical Association.
Date of download: 3/21/2013"
15, dependent personality disorder; 16, obsessive compulsive personality disorder; 17, paranoid personality disorder; 18, schizoid
All rights reserved."
personality disorder; 19, histrionic personality disorder; 20, antisocial personality disorder."

11. Moms
who
drink
a
lot
• NLSCY
study
– Over
Canadian
10000
families

12. 12

13. 13

14. 14

15. 15

16. Immature
Problems
Labeled
Bureaucra(c
Induced
Disorders
900,000
ADHD’s
misdiagnosed
and
treated
in
the
US.
(
Elder,
2010,
Journal
of
Health
Economics)

18. Family
Pedigree

19. 19

20. 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.

21. Alcohol Challenge – Basic Design
Pre-­‐tes(ng/
Alcohol/
Post-­‐tes(ng
Subject
Control
Placebo
Manipula(o
Selec(on
Manipula(o
Challenge
n
n
21

22. Dampening

23. Drinking
to
Cope
&
Brain
Response
to
Emo$onal
Faces

24. Amygdalar
Response
to
Dis(nct
Facial
Expressions
in
Anxiety-­‐Sensi(ve
Subjects

25. M-­‐AS
VS
F-­‐AS
0.0
Alcohol
Placebo
Alcohol
Placebo
0.2
-0.2
BOLD Signal Intensity (a.u.)
BOLD Signal Intensity (a.u.)
0.0 -0.4
AG HC Putamen Caudate NAc lOFG
Brain Region
-0.2 -0.6
-0.4 -0.8
-1.0
-0.6
AG HC Putamen Caudate NAc mFOG
Brain Region

26.
S$mula$on

27. Aggressive
Behavior
and
the
High
Heart
Rate
Response
age 10 to 17 delinquency scores TAP - Mean Shock Level Selected
Zscore (Average of 1988 to 1995 longitudinal scores)
** * **
Zscore (Mean Shock Selected)
0.8
Physical Aggression 0.6
0.6 Destruction of Property Sober
Theft
0.4
Intoxicated
0.4
0.2 0.2
0.0 0.0
* p < 0.03
-0.2 ** p < 0.02
-0.2
-0.4
-0.4
-0.6 Low Heart Rate Responders High Heart Rate Responders
to Alcohol Intoxication to Alcohol Intoxication -0.6
-0.8
Low HR Responders High HR Responders

29. A.
High
&
B.
Low
nega$ve
effects
of
alcohol
a b
5.7" -7.2"
t" t"
3.1" -3.1"

30. Alcohol Self-
Administration
BAL
Progressive Ratio Breakpoint (log)
Ethanol-Induced ∆ Heart Rate
30 APTD
3 APTD+DOPA
20 2.5
2 *
10 **
1.5
0 1
r = 0.713, p ≤ 0.002
0.5
-10
-1 -0.5 0 0.5 1 1.5
0
∆ Alcohol Self-Administration
(log PR breakpoint) High HR Low HR
Barrett et al, 2005

31. 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.

32. 0.4 Alcohol Induced Changes in BAES Stimulation
Z scores on the SPSRQ
0.3 Low HR responders 50
0.2 High HR responders 40
0.1 30
0 20
-0.1 HHRR
10
-0.2 LHRR
0
-0.3
-­‐ 10
-0.4
-­‐ 20
SP SR
-­‐ 30
Dimensions of the SPSRQ pre-­‐alc ohol 30min 40min 60min 90min 120min 150min

33. The
High
Heart
Rate
Response
and
the
Subjec$ve
High
Subjective High Assessment Scale Subjective High across the blood alcohol curve
0.8 Subjective effects of alcohol
Zscore (Subjective High Assessment Scale)
"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 High Heart Rate Responders
to Alcohol Intoxication to Alcohol Intoxication

34. 0.4
Z scores on the SPSRQ
0.3 Low HR responders
0.2 High HR responders
0.1
0
-0.1
-0.2
-0.3
-0.4
SP SR
Dimensions of the SPSRQ
34

35. Design
Alcohol-Induced HR Change as a Function of HR Group
• N= 56 males and Drinking Condition (Reward/Non-Reward)
• Day I
– Alcohol challenge
14
– Subjects divided 12
HR increase in BPM
(medium split) into High
10
and Low HR response HR day 1
8
• Day II HR day 2 n-r
6
HR day 2 r
– While sober, participated 4
in a task where auditory 2
and visual cues were 0
paired With reward or no Low HR High HR
reward responders responders
– Subjects then randomly HR response to alcohol intoxication groups
assigned and alcohol
challenged and were
exposed to conditioned
cues.

36. 0.5
0.4 Low HR responders
Z scores on the SURPS
0.3 High HR responders
0.2
0.1
0
-0.1
-0.2
-0.3
-0.4
-0.5
H/I AS IMP SS
Dimensions of the SURPS

38.
38

39. (% of women no longer meeting criteria
60
for substance abuse or dependence)
50
Rate of Remission
40
30
20
10
0
Motivation Motivation Educational
Matched MisMatched Film
Brief Intervention
39

40. 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 Legend:"
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."
Copyright © 2012 American Medical Association.
Date of download: 3/21/2013"
All rights reserved."

44. 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.

46. 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,

47. A
DOG