L`alcoolisme est il une maladie

L’alcoolisme est il une maladie ?
Etat de la controverse
SFA, 21/03/2013
P. Perney. Addictologie, CHU Nîmes
ì
Déclaration de conflits d’intérêt
• 
DA Pharma
• 
Lundbeck
• 
Merck Serono
• 
Roche
• 
Bouchara Recordati
Introduction
Alcoolisme est une maladie chronique, se
caractérisant par une recherche compulsive
d’alcool, avec une perte progressive de
contrôle et par la survenue de rechutes
(Alcoolisme : abus ou dépendance)
Épidémiologie
Problème majeur de santé publique
o  49000 décès par an (France)
o  2 500 000 par an dans le monde*
o  9% des décès des Jeunes de 15 – 29 ans*
o  Binge drinking : 11 % de la population
mondiale*
*Global Status Report on Alcohol and Health, OMS 2011
Dépendance et appartenance ethnique
(Caetano et Cunradi., Addiction 2002)
%
Génétique
1073
Genetic studies of addiction
HORIZONS REVIEW
doi:10.1111/j.1360-0443.2008.02213.x
Are there genetic influences on addiction:
evidence from family, adoption and twin studies
Alcoholism
Nicotine Dependence
Arpana Agrawal & Michael T. Lynskey
Cannabis use disorders
Department of Psychiatry, Washington University School of Medicine, St Louis, MO, USA
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Correspondence to: Arpana Agrawal, Department of Psychiatry, Washington University School of Medicine, 660 S. Euclid, Box 8134, St Louis, MO 63110,
USA. E-mail: [email protected]
Submitted 24 September 2007; initial review completed 24 January 2008; final version accepted 11 February 2008
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and other illicit drug use disorders across
Keywords
Addiction, environment, genetic, heritability, twins.
samples
of twins
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Aims In this exciting era of gene discovery, we review evidence
60 from family, adoption and twin studies that examine
the genetic basis for addiction. With a focus on the classical twin design that utilizes data on monozygotic and dizygotic
50
twins, we discuss support in favor of heritable influences on alcohol, nicotine, cannabis and other illicit drug
40 also influence earlier stages (e.g. experimentation)
dependence. Methods We review whether these genetic factors
of the addictive process and whether there are genetic
30influences specific to each psychoactive substance.
Results Converging evidence from these studies supports the
20role of moderate to high genetic influences on addiction
with estimates ranging from 0.30 to 0.70. The changing role of these heritable factors as a function of gender, age and
10
cultural characteristics is also discussed. We highlight the importance of the interplay between genes and the environment as it relates to risk for addiction and the utility of0 the children-of-twins design for emerging studies of
gene–environment interaction is presented. Conclusions Despite the advances being made by low-cost highthroughput
whole genome
association
Figure
2 Heritability
estimates
for assays,
alco- we posit that information garnered from twin studies, especially
extended twin designs with power to examine gene–environment interactions, will continue to form the foundation for
holism, nicotine dependence, cannabis
genomic research.
tw
in
s
80
70
Fi
nn
is
ABSTRACT
Heritability (% of total variance)
Any illicit drug use disorders
Héritabilité de la dépendance à l’alcool : 51 à 64 % dans les études de jumeaux Prescott
tialal.,
evidence
from
twin2006;36:473
studies that nicotine dependence
et
Behav
Gen
is a heritable phenotype. Kendler et al. [53] reported a
studies of cannabis-related phenotypes and noted that
existing studies have produced estimates of the heritabil-
Dopamine/Génétique
Neurobiologie
ì  Circuit neurobiologique bien identifié (modèles
animaux, homme)
ì  Alcool : ì
dopamine extracellulaire dans
régions clés du système limbique (récompense),
en particulier NAc
ì  Plus la libération de dopamine est rapide et
plus l’alcool va donner un effet renforçant
Volkow et al., Bioassays 2010;32:748
used
PETref.
to evaluate
DA’s role
in drugwith netics
of drugsfrom
labeled
with positron
addicted subjects. Reprinted
from
13, Copyright
(2009),
permission
Elsevier.
presentations are available on the NAS Web site at www.
Addiction: Beyond dopamine reward circuitry
sponses (5).
Fig. 5.
National Institutes of Health, Bethesda, MD 20892; and cMedical Department, Brookhaven National Laboratory, Upton, NY 11973
her vulnerability to addiction (25).
phetamine abusers, low striatal D2R was
PNAS | September 13, 2011 | vol. 108 | no. 37 | 15037–15042
Edited by Donald W. Pfaff, The Rockefeller University, New York, NY, and approved November 9, 2010 (received for review August 31, 2010)
www.pnas.org/cgi/doi/10.1073/pnas.1010654108
Dopamine (DA) is considered crucial for the rewarding effects of drugs of abuse, but its role in addiction is much less clear. This review
focuses on studies that used PET to characterize the brain DA system in addicted subjects. These studies have corroborated in humans the
relevance of drug-induced fast DA increases in striatum [including nucleus accumbens (NAc)] in their rewarding effects but have
unexpectedly shown that in addicted subjects, drug-induced DA increases (as well as their subjective reinforcing effects) are markedly
blunted compared with controls. In contrast, addicted subjects show significant DA increases in striatum in response to drug-conditioned
cues that are associated with self-reports of drug craving and appear to be of a greater magnitude than the DA responses to the drug. We
postulate that the discrepancy between the expectation for the drug effects (conditioned responses) and the blunted pharmacological
effects maintains drug taking in an attempt to achieve the expected reward. Also, whether tested during early or protracted withdrawal,
addicted subjects show lower levels of D2 receptors in striatum (including NAc), which are associated with decreases in baseline activity in
frontal brain regions implicated in salience attribution (orbitofrontal cortex) and inhibitory control (anterior cingulate gyrus), whose
disruption results in compulsivity and impulsivity. These results point to an imbalance between dopaminergic circuits that underlie reward
and conditioning and those that underlie executive function (emotional control and decision making), which we postulate contributes to the
compulsive drug use and loss of control in addiction.
prefrontal cortex
D
| dorsal striatum | substance use disorders | stimulant drugs | brain imaging
FROM THE ACADEMY: SACKLER LECTURE
nasonline.org/quantification.
papers from this coltake (29). See
Inall addition,
because impairreward and addiction. These findings show emitters show that peak levels in human
loquium in supplement 3 of volume 108.
that addiction affects not only the DA
brain are reached within 10 min after i.v.
ments in OFC and ACC are associated
Author contributions: N.D.V., G.-J.W., and J.S.F. designed
reward circuit but circuits involved with
administration and that this fast drug
research; N.D.V.,
J.S.F., D.T., and behaviors
F.T. performed
withG.-J.W.,
compulsive
and impulsivity
conditioning/habits, motivation, and exec- uptake is associated with the high (13)
research; N.D.V., G.-J.W., J.S.F., D.T., and F.T. analyzed data;
DA
and
Inhibitory
Control
in
Addiction
natural reinforcers (16).
Preclinical
studies
wrotepostulated
the paper.
utive functions (inhibitory control, sa(Fig. 1). Indeed, for an equivalent level of and N.D.V.we
that DA’s impaired modulience attribution,
and decision making).
cocainetoreaching
theprepotent
brain (assessed
as
The authors declare no conflict of interest.
have revealed that glutamatergic
projecThe capacity
inhibit
responses
lation of these regions could underlie the
Other neurotransmitters (and neuropepequivalent level of DA transporter blockThis article is a PNAS Direct Submission.
tions from prefrontal cortex
into
VTA/SN
is
likely
to
contribute
to
an
individual’s
ability
c
b
b
compulsive
and impulsive drug intake seen
1
tides)
areVolkow
involveda,b,1
with
drug reward
(i.e.,c, Joanna
ade), when
cocaine
enteredTomasi
the brain
To whom
correspondence should be addressed. E-mail:
Nora D.
, Gene-Jack
Wang
S. Fowler
, Dardo
, and Frank
Telang
a conditioned
b
rapidly
anddrugs,
i.v. administration),
it or
[email protected].
cannabinoids,
opioids)
andAbuse,
with the
neuand NAc mediate these
to
restrain
from
taking
and
thus
his
inonaddiction
(30,
31). Indeed, in methamNational Institute
on reDrug
National
Institutes
of(smoked
Health,
Bethesda,
MD
20892;
National
Institute
Alcohol Abuse
and Alcoholism,
elicited a more intense high than when it
rugs of abuse (including alcoroadaptations from repeated drug use
entered the brain more slowly (snorted)
hol) are inherently rewarding,
(i.e., glutamate, opioids, GABA, cortico(14). This is consistent with preclinical
which is why they are consumed tropic-releasing factor). These are not
by humans or self-administered discussed here (except for glutamate), but studies showing that the faster the drug’s
entry into the brain, the stronger are its
several reviews address them (5, 6).
by laboratory animals (1). Only a small
reinforcing effects (15). This probably repercentage of individuals exposed to drugs
flects the fact that abrupt and large DA
will become addicted, that is, shift from
DA and Acute Drug Reward
increases triggered by drugs mimic the fast
controlled drug use to compulsive drug
All drugs that can lead to addiction inand large DA increases associated with
use with loss of control over intake despite crease DA in NAc, which is achieved
phasic DA firing that are associated in the
adverse consequences, however (2). Facthrough their interaction with different
brain with conveying information about
tors that determine who becomes addicted molecular targets by the various drug
reward and saliency (16).
include genetic (50% of risk), developclasses (6) (Table 1). In humans, PET
Drug-induced DA increases in NAc
mental (risk is higher in adolescence), and studies have shown that several drugs
occur in nonaddicted as well as addicted
environmental (e.g., drug access, stress)
[stimulants (7, 8), nicotine (9), alcohol
subjects, which raises the question of how
factors (2).
(10), and marijuana (11)] increase DA in
The mesolimbic dopamine (DA) pathdorsal and ventral striatum (where NAc is they relate to addiction.
To start with, there is increasing evidence
way [DA cells in ventral tegmental area
located). These studies used a radiotracer
that DA’s role in reinforcement is more
(VTA) projecting into nucleus accumbens that binds to DA D2 receptors (D2Rs)
complex than just coding for reward per se
(NAc)] seems to be crucial for drug reward but only when these are not occupied by
(hedonic pleasure) and that stimuli that
(1). Other DA pathways [mesostriatal
DA (i.e., [11C]raclopride). By comparing
induce fast and large DA increases also
(DA cells in substantia nigra {SN} probinding after placebo and after the drug,
jecting into dorsal striatum) and mesothese studies estimate the decreases in D2R trigger conditioned responses and elicit incentive motivation to procure them (17).
cortical (DA cells in VTA projecting into availability induced by the drug, which are
Model proposing afrontal
network
of interacting circuits underlying addiction: reward (nucleus accumbens,
and ventral
pallidum),
ThroughVTA,
conditioning,
a neutral
stimulus conditioning/memory
cortex)] are now also recognized to proportional to DA increases (12). Most
Imagerie cérébrale
• 
Images spécifiques des sujets malades
Anatomiques : modifications significatives
o  Fonctionnelles
o 
• 
Imagerie fonctionnelle
Prise d’alcool
o  Augmentation de dopamine
o  Expérience subjective d’euphorie
o 
Koob et al., Neuropsychopharmacol Rev 2010;35:217
Clinique-Compulsion
§ 
Addiction is a brain disease, and it matters
Leshner AI., Science 1997;278:45
§ 
Désir irrésistible, tel qu’il est impossible de
ne pas consommer
§ 
Le malade n’a pas le pouvoir d’y résister
§ 
Pas de choix volontaire, ni de solution
alternative
Hyman SE., Am J Psychiatr 2005;162:1414
Compulsion
ì  Exposition à une substance augmente la
dopamine synaptique et motive fortement
le comportement
ì  Effet >> aux « renforceurs naturels »
Koob et al., Neuropsychopharmacol Rev 2010;35:217
Maladie de l’apprentissage et de la
mémoire « signal better than expected »
Lorsque la maladie est sévère, la recherche du produit prend
une telle force que cela peut motiver les parents à négliger les
enfants, des sujets sans antécédents judiciaires à commettre des
crimes, et des individus avec une consommation d’alcool
douloureuse à poursuivre cette consommation.
Hyman SE,. Am J Psychiatry 2005;162:1414
Evolution
§ 
Taux de rechute très important
§ 
Témoin de la grande difficulté à gérer son
comportement
Traitement
Amélioration significative avec des molécules
qui agissent au niveau du circuit de la
récompense
§ 
§ 
§ 
§ 
§ 
§ 
Acamprosate
Baclofène
Disulfirame
Nalmefene
Naltrexone
Ondansetron
En résumé: arguments en faveur
o  Épidémiologie
o  Génétique
o  Neurobiologie
o  Neuro-imagerie
o  Clinique
o  Évolution
o  Traitement
Épidémiologie
o  Epidémiologie évolutive
•  Moins de consommation le midi
• 
Évolution vers le binge drinking
o  Dépendance (DSM IV), pic dans l’adolescence
et adulte jeune, puis dans la majorité des cas,
résolution permanente, sans intervention fin de
vingtaine, trentaine
Pickard H., AJOB Neurosci 2012;3:40
Abus d’alcool
Canada.gc.ca 2011
%
Age
Region
dence) and was not associated with sociodemographic
Design, Setting, and Participants: Face-to-face incharacteristics but
associated with psychiatric
terviews
using
the
Alcohol
Use
Disorder
and
Associated
Northeast Disabilities Interview Schedule of the National0.7
(0.5-1.1)
0.7was(0.4-1.1)
0.9co-(0.5-1
morbidity.
Institute
ORIGINAL ARTICLE
Alcohol Abuse and Alcoholism in a large representaMidwest on
0.6 (0.4-0.9)
0.5 (0.3-0.8)
1.0 (0.5-2
Conclusions: Most individuals with drug use disorders
tive sample of US adults (N = 43 093).
haveComorbidity
never been0.4
treated,
and treatment disparities
exist(0.4-1
Prevalence,
Correlates, Disability,
and
South
0.5 (0.3-0.7)
(0.3-0.6)
0.7
Main Outcome Measures: Twelve-month and lifeamong those at high risk, despite substantial disability and
time Drug
prevalence ofAbuse
drug abuse and
dependence
the
comorbidity. Comorbidity
of drug use disorders with
1 and
[Reference]
1 [Reference]
1other
[Refere
ofWest
DSM-IV
and
Dependence
associated correlates, treatment rates, disability, and cosubstance use disorders and antisocial personality disormorbidity with
other Axis I and II disorders.
in the United
States
der, as well as dependence with mood disorders and generalized anxiety disorder, appears to be due in part to unique
Results: Prevalences of 12-month and lifetime drug abuse
factors underlying each pair of these disorders studied. The
and 7.7%, respectively)
exceededSurvey
rates of drug
persistence
of low treatment
rates despite the availability
Results From (1.4%
the National
Epidemiologic
ondeAlcohol
and Related
Conditions
pendence (0.6% and 2.6%, respectively). Rates of abuse
of effective treatments indicates the need for vigorous edudependence
were
greater
among men,
Na- PhD;cational
for the
Wilson M. Compton,and
MD,
MPE; Yonette
F. generally
Thomas, PhD;
Frederick
S. Stinson,
Bridgetefforts
F. Grant,
PhD,public
PhD and professionals.
tive Americans, respondents aged 18 to 44 years, those
of lower socioeconomic status, those residing in the West,
Arch Gen Psychiatry. 2007;64:566-576
Abbreviations: CI, confidence interval; OR, odds ratio.
*Significant ORs are given in boldface.
T
pone
(!=−
and r
Drug
tal co
(!=−
and r
Thus
dence
dents
clearl
andHEthose
who
or widowed,
sepaceration,
poverty,
homelessness, a lower
ABUSE
OFwere
AND never
DEPENmarried
rated,
or divorced
P!.05). Associations
drug
use
probabilityofof
recovery,
poor treatment
dence
on illicit (all
substances
disorders
with other
substance
disorders
antioutcome,
andand
poor
quality of life.14-18 Drug
are widespread
among
the use
social
personality
disorder
diminished
but re- also increases the
disorder comorbidity
general
population
and arewereuse
Drug
Abuse
mained
strong
when
we
controlled
for
psychiatric
dis- especially among
0.009
risk
of
suicide
attempts,
associated
with
substanAuthor Affiliations: Division of
orders.
Dependence
associations
with
most
mood
Objectives: To present
detailed
information
ontial
drugsocietal,
individuals
with
bipolar
disorder.19
personal,
and economic
Epidemiology,
Services,
and
Drug
Dependence
1-4
0.008
disorders
and generalized
disorder extensive
also re- data on drug use in
abuse and dependence
prevalence,
coNational
epidemiologic
sur-anxiety Although
costs.
Prevention
Research,correlates,
National and
9-13
significant.
Lifetime
treatmenthelp-seeking
morbidity with other
Axis Ionand
II Abuse
disorders.
numerous
clinical studies
veys5-8 and mained
the USorpopulation
have been available on
Institute
Drug
0.007
(Drs Compton and Thomas),
consistentlybehavior
indicate was
that uncommon
drug use disoran ongoing
basis
for adults and adoles(8.1%, abuse;
37.9%,
depen20,21
of
epidemiologic data on the prevaders
alco- with
cents,
dence)associations
and was notwith
associated
sociodemographic
Design, Setting, and
andLaboratory
Participants:
Face-to-face
in-have strong
Epidemiology
and
Biometry,
0.006
lence,
treatment, and
hol
use
disorders
and
mood,
anxiety,
and
characteristics but was associated with correlates,
psychiatricdisability,
coterviews using the Alcohol Use Disorder and Associated
Division of Intramural Clinical
comorbidity of drug use disorders among
personality morbidity.
disorders (PDs). Axis I and II
Disabilities Interview
Schedule
of
the
National
Institute
and Biological Research,
0.005
adults are seldom collected. In fact, it has
comorbidity with drug use disorders has
on Alcohol
Abuse and
Alcoholism
large representaNational
Institute in
onaAlcohol
been
more
16 years since such debeen associated
with underachievement,
Conclusions:
Most individuals with
drug
usethan
disorders
tive sample of US adults
(N=43
093).
Abuse
and
Alcoholism
0.004
tailed
information
on drug use disorders in
decreased
work
productivity,
poor
health,
have never been treated, and treatment disparities exist
(Drs Stinson and Grant),
the United
States has
been published. In one
impairment,
human
Main Outcome Measures:
Twelve-month
lifeNational Institutes
of Health, andneuropsychological
among those
at high risk,
despite substantial
disability
and
0.003
of those
studies,
1990-1992 National Coimmunodeficiency
virusComorbidity
infection, hepaHealth
and
time prevalence of Department
drug abuseofand
dependence
and
the
comorbidity.
of drug use
disorders
withthe
other
7
DSM-III-R22 criteria were
morbidity
Survey,disortitis,
dysfunction,
Human
Services,
Bethesda,
Md. and
associated
correlates,
treatment
rates,
disability,
co-social substance
use violence,
disorders incarand antisocial
personality
0.002
morbidity with other Axis I and II disorders.
der, as well as dependence with mood disorders and generalized anxiety disorder, appears to be due in part to unique
0.001
(REPRINTED) ARCH GEN PSYCHIATRY/ VOL 64, MAY 2007
WWW.ARCHGENPSYCHIATRY.COM
Results: Prevalences of 12-month and lifetime drug abuse
factors underlying
566each pair of these disorders studied. The
(1.4% and 7.7%,
persistence of low treatment rates despite the availability
0 respectively) exceeded rates of drug de©2007 American
Medical
Association.
All rights
reserved.
pendence (0.6%
and
2.6%,
respectively).
Rates
of
abuse
effective
treatments
indicates
the
need for
5From:
10
15
20
25Na-a CTRE
30 of
40
45 User
50professionals.
55vigorous
60eduDownloaded
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HOSP35
UNIV
NIMMES
FRANCE
on 02/01/2013
and dependence
were generally
greater among men, by
cational
efforts
for the
public and
tive Americans, respondents aged 18 to 44 years, those Age, y
of lower socioeconomic status, those residing in the West,
Arch Gen Psychiatry. 2007;64:566-576
Hazard Rate
Background: Current and comprehensive information on the epidemiology of DSM-IV 12-month and lifetime drug use disorders in the United States has not been
available.
HE ABUSE OF AND DEPEN-
ceration, poverty, homelessness, a lower
of recovery,
on illicit
Figure 1. Hazard rates for age atdence
onset
ofsubstances
DSM-IV probability
drug abuse
andpoor treatment
14-18
« Regarding the large variability of phenotype assessments in these
Studies, the types of studied populations, and the important
number of genetic polymorphisms or genes related to dopamine
pathway, it
is difficult to draw any warm conclusion »
« It is important to point out that, with the exception of
genes involved in protection against alcohol or nicotine
addictions, via their effects on drug metabolism, the risk
of SUDs attributable to other classes of genes identified
to date is very small »
Génétique de l’alcoolisme ?
§ 
L’abstinence est-elle une maladie
génétiquement transmissible ?
§ 
Mal-adaptation sociale
§ 
Risques accrus de cancer VADS, de maladies
cardiovasculaires
Yokoyama et al., Dis Esophagus 2013;26:148
Zhang et al., Pharmacol Ther 2011;132:86
Neuro-imagerie
ì  Cerveaux étudiés :
ì  Gros consommateurs
ì  Conséquence de la consommation
ì  Les séquelles d’un traumatisme crânien peuvent-
elles être considérées comme la cause de la
chute responsable du traumatisme ?
Holden T., CMAJ 2012;184:679
Neuro-imagerie
• 
Réversibilité des lésions « d’atrophie »
• 
N=28
• 
3 semaines après arrêt de l’alcool
Trabert et al., Acta Psychiatr Scand 1995
Environnements enrichis
ì  Rats addicts s’auto administrent des
produits jusqu’à la mort
ì  Environnement enrichis, les animaux
choisissent l’eau même s’ils connaissent la
douleur du syndrome de sevrage
Alexander et al., Psychopharmacology 1978.
Solinas et al. Proceedings Nat Acad Sci USA 2008
Behavioral Neuroscience
2011, Vol. 125, No. 2, 184 –193
© 2011 American Psychological Association
0735-7044/11/$12.00 DOI: 10.1037/a0022627
Differential Rearing Conditions and Alcohol-Preferring Rats:
Consumption of and Operant Responding for Ethanol
Gerald A. Deehan, Jr., Matthew I. Palmatier, Mary E. Cain, and Stephen W. Kiefer
DEEHAN, PALMATIER, CAIN, AND KIEFER Kansas State University
Exposing rats to differential rearing conditions during early postweaning development has been shown
to produce changes in a number of behaviors displayed during adulthood. The purpose of the present
studies was to investigate whether rearing alcohol-preferring (P) and nonpreferring (NP) rats in an
environmental enrichment condition (EC), a social condition (SC), or an impoverished condition (IC)
would differentially affect self-administration of 10% ethanol. In Experiment 1, rats were tested for
consumption of 10% ethanol in limited- and free-access tests. For Experiment 2, rats were trained to
respond in an operant chamber for ethanol and then provided concurrent access to 10% ethanol and water.
Each solution was presented in a separate liquid dipper after meeting the schedule of reinforcement on
distinct levers. After concurrent access tests, the water lever/dipper was inactivated and a progressive ratio
(PR) schedule was initiated. Three successive solutions (10% ethanol, 15% ethanol, and 10% sucrose) were
tested under the PR. For P rats, rearing in an EC reduced ethanol consumption, preference, and motivation to
obtain ethanol, relative to P rats reared in an IC. Thus, exposure to a novel environment immediately after
weaning acted to decrease the reinforcing properties of ethanol in an animal model for alcoholism.
Keywords: differential rearing conditions, environmental enrichment, ethanol, alcohol-preferring rat
The determinants of alcohol use disorders are undoubtedly
complex, involving predispositional factors that arise from both
genetic and environmental sources. Hereditary mechanisms have been
linked to both ethanol consumption and alcohol use disorders in
human and animal models (Li, Lumeng, & Doolittle, 1993; Stacey,
Clarke, & Schumann, 2009). Similarly, environmental conditions
have been shown to influence ethanol intake as a variety of manipulations effectively alter an organism’s response to ethanol (Deatherage, 1972; Ellison, 1981; Kulkosky, Zellner, Hyson, & Riley, 1980).
To date, few studies have investigated the interaction between hereditary factors and environmental influences on the proclivity to consume and/or motivation to obtain ethanol in rodents.
Currently, there are several selectively bred rat lines that are
genetically predisposed to consume ethanol and are considered
useful as animal models of alcoholism. Selectively bred lines
consist of divergent groups of rodents that exhibit either a strong
preference for and high consumption levels of ethanol (preferring
(plus (nonpreferor minus
line) or do not prefer andFigure
consume4.veryMean
little ethanol
consumption, the P rat line meets the major criteria for an animal
model of alcoholism (Li et al., 1993). For instance, when provided
24-hr free access to ethanol, P rats will consume over 5 grams of
ethanol per kilogram of body weight per day (Li, Lumeng,
McBride, & Murphy, 1987; Li, Lumeng, McBride, Waller, &
Murphy, 1986). Additionally, when given either limited-access or
24-hr free access to ethanol, P rats will consume enough ethanol to
establish blood alcohol levels (BACs) in the 50 –70 mg% range,
with some rats reported to establish a BAC up to 200 mg% (Bell,
Rodd, Lumeng, Murphy, & McBride, 2006; Rodd-Henricks, et al.,
2002). It has also been shown that P rats readily learn to respond
in an operant chamber for ethanol (Files, Samson, Denning, &
Marvin, 1998; Murphy, Gatto, McBride, Lumeng, & Li, 1989;
Oster et al., 2006; Penn, McBride, Lumeng, Gaff, & Li, 1978).
Although selectively bred rat lines represent a feasible way to
examine the contribution of genetic aspects to alcoholism, differential rearing environments provide a paradigm to examine the
standard error of the mean) amount of
82 études
Age : 10-25 ans
Deux grands groupes :
Garçons extravertis recherchant des sensations
Filles anxieuses gérant les émotions négatives
Facteurs de risques de binge drinking chez 44600 lycéens allemands
Facteurs environnementaux/sociaux
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
• 
Séparation parents
Communication intra familiale
Nombres d’amis
Comportements déviants parmi les amis
Cohésion du voisinage
Sécurité du voisinage
Capacité des professeurs à intervenir lors
d’affrontement violents entre élèves
Comportements agressifs des enseignants
Croyance religieuse
Intégration sociale à l’école
Absentéisme
Prises de risque
Redoublements
Facteurs génétiques
•  Parents fumeurs
•  Pensées suicidaires
Donath et al., BMC Public Health 2012;12:263
morbidity.
w Schedule of the National Institute
nd Alcoholism in a large representaults (N=43 093).
Conclusions: Most individuals with drug use disorders
have never been treated, and treatment disparities exist
ORIGINAL
ARTICLEand
among those at high risk, despite substantial
disability
comorbidity. Comorbidity of drug use disorders with other
substance use disorders
and antisocial personality
disor- and Comorbidity
Prevalence,
Correlates,
Disability,
der, as well as dependence with mood disorders and genof
DSM-IV
Drug
Abuse
and
eralized
anxiety disorder,
appears
to be due
in partDependence
to unique
factors
underlying
each States
pair of these disorders studied. The
in
the
United
persistence of low treatment rates despite the availability
of effective
treatments
indicates
the need for vigorous
eduResults
From
the National
Epidemiologic
Survey on
Alcohol and Related Conditions
cational efforts for the public and professionals.
easures: Twelve-month and life-
rug abuse and dependence and the
, treatment rates, disability, and cor Axis I and II disorders.
of 12-month and lifetime drug abuse
pectively) exceeded rates of drug de2.6%, respectively). Rates of abuse
e generally greater among men, Naondents aged 18 to 44 years, those
mic status, those residing in the West,
vision of
and
ational
e
mas),
etry,
Clinical
,
cohol
),
ealth,
nd
da, Md.
T
Wilson M. Compton, MD, MPE; Yonette F. Thomas, PhD; Frederick S. Stinson, PhD; Bridget F. Grant, PhD, PhD
Arch Gen Psychiatry. 2007;64:566-576
Background: Current and comprehensive informa-
and those who were never married or widowed, sepa-
rated,
or divorced (all P!.05). Associations of drug use
tionDEPEN
on the epidemiology
of DSM-IV
12-month
and lifeceration,
poverty,
homelessness,
a lower
HE ABUSE OF AND
-
au cours
12
mois
précédents
probability of recovery,
poor treatment
dence on illicitUne
substances
social des
personality
disorder
were diminished
but reavailable.dépendance
14-18 strong when we controlled for psychiatric disoutcome, and poor quality of life.mained
Drug
are widespread among the
orders. Dependence associations with most mood
Objectives: To present detailed information on drug
use disorder comorbidity also increases
the
general population
and are
disorders and generalized anxiety disorder also reabuse and dependence prevalence, correlates, and corisk
of
suicide
attempts,
especially
among
associated withmorbidity
substanmained
significant. Lifetime treatment- or help-seeking
with other Axis I and II disorders.
19
behavior
was uncommon (8.1%, abuse; 37.9%,
depenFacteur de
risque
OR
individuals
with bipolar disorder.
tial societal, personal, and economic
dence) and was not associated with sociodemographic
Design, Setting, and Participants: Face-to-face in1-4
surAlthough
extensive
data
on
drug
use
in
costs. National epidemiologic
characteristics but was associated with psychiatric coterviews using
the Alcohol Use Disorder and Associated
studies9-13
veys5-8 and numerous clinical Disabilities
the
US population
have
been available
morbidity.on
Interview
Schedule
of the National
Institute
Alcohol
Abuse and
a large for
representaconsistently indicate that drugon
use
disoranAlcoholism
ongoinginbasis
adults and adolesConclusions: Most individuals with drug use disorders
sample of US adults (N=43
20,21 093).
epidemiologic data on have
the prevaders have strong associations tive
with
alcoHomme
/cents,
Femme
2.5exist
never been treated, and treatment disparities
lence, correlates,
disability,
andat high risk, despite substantial disability and
hol use disorders and mood, anxiety,
and Measures:
Main Outcome
Twelve-month
and life-treatment,
among those
timeIprevalence
abuse and dependence
and the
comorbidity.
comorbidity
of drug use
disorders
amongComorbidity of drug use disorders with other
personality disorders (PDs). Axis
and II of drug
associated correlates, treatment rates, disability, and cosubstance use disorders and antisocial personality disoradults
are
seldom
collected.
In
fact,
has
comorbidity with drug use disorders
has
morbidity with other Axis I and II disorders.
der, asitwell
as dependence with mood disorders and genbeen
more
than
16
years
since
such
de- disorder, appears to be due in part3.8
been associated with underachievement,
eralized
anxiety
to unique
Natif
/
Caucasien
Results:
Prevalencestailed
of 12-month
and lifetimeon
drug
abuse
factors underlying
information
drug
use disorders
in each pair of these disorders studied. The
decreased work productivity, poor
health,
(1.4% and 7.7%, respectively) exceeded rates of drug depersistence of low treatment rates despite the availability
United
States Rates
has been
published.
In one
neuropsychological impairment,
human
pendence
(0.6% andthe
2.6%,
respectively).
of abuse
of effective
treatments indicates the need for vigorous eduofgenerally
those studies,
the 1990-1992
Co- for the public and professionals.
immunodeficiency virus infection,
hepa- were
and dependence
greater among
men, Na- National
cational efforts
tive Americans,
respondents
18 to 447 years,
those 22 criteria were
DSM-III-R
morbidity
Survey,
titis, social dysfunction,Jamais
violence,
incarmarié
/ Enagedcouple
2.3
time drug use disorders in the United States has not been
of lower socioeconomic status, those residing in the West,
Veuf – divorcé – séparé / en couple
NTED) ARCH GEN PSYCHIATRY/ VOL 64, MAY 2007
566
T
WWW.ARCHGENPSYCHIATRY.COM
disorders with other substance use disorders and anti-
Arch Gen Psychiatry. 2007;64:566-576
HE ABUSE OF AND DEPEN-
dence on illicit substances
are widespread among the
general population and are
©2007 American Medical Association. All rights reserved.
associated with substanAffiliations:
of
network.com/ by a CTRE HOSP UNIV NIMMESAuthor
FRANCE
UserDivision
on 02/01/2013
tial societal, personal, and economic
Epidemiology, Services, and
1-4
costs. National epidemiologic surPrevention Research, National
veys5-8 and numerous clinical studies9-13
Institute on Drug Abuse
(Drs Compton and Thomas),
consistently indicate that drug use disorand Laboratory of
ders have strong associations with alcoEpidemiology and Biometry,
hol use disorders and mood, anxiety, and
Division of Intramural Clinical
personality disorders (PDs). Axis I and II
and Biological Research,
comorbidity with drug use disorders has
National Institute on Alcohol
been associated with underachievement,
Abuse and Alcoholism
decreased work productivity, poor health,
(Drs Stinson and Grant),
neuropsychological impairment, human
National Institutes of Health,
Primaire / études supérieures
Salaire < 20 K$ / > 70 K$
3.6
ceration, poverty, homelessness, a lower
probability of recovery, poor treatment
outcome, and poor quality of life.14-18 Drug
use disorder comorbidity also increases the
risk of suicide attempts, especially among
individuals with bipolar disorder.19
Although extensive data on drug use in
the US population have been available on
an ongoing basis for adults and adolescents,20,21 epidemiologic data on the prevalence, correlates, disability, treatment, and
comorbidity of drug use disorders among
adults are seldom collected. In fact, it has
been more than 16 years since such detailed information on drug use disorders in
the United States has been published. In one
IC 95 %
1.6 – 3.9
1.6 – 9.1
1.1 – 4.6
2.0 – 6.6
1.9
1.0 – 3.5
5.8
1.2 – 22.2
Self medication hypothesis
Khantzian et al., Am J Psychiatr 1985
ì  Alcool : moyen de gérer des troubles
psychologiques, économiques, sociaux ou
relationnels
Pickard H., AJOB Neurosci 2012
ì  Auto médication du stress
Cooper et al., J Abnorm Psychol 1988; Perkins, J Stud
Alcohol 1999; Kuntsche et al., Addict Behav 2006 Keyes et
al., Psychopharmacol 2011. Enoch MA. Psychopharmacol
2011
Principales causes d’alcoolisme
1.  Augmentation de sensations positives
2.  Réduction des affects négatifs
3.  Amélioration du tissu social
4.  Réduction de l’isolement social
Cox et al., J Abnorm Psychol 1988. Cooper ML., Psychol Assess 1994.
Theakston et al., Personal Individ Differ 2004
Compulsion
o  Exposition à une substance augmente la
dopamine synaptique et motive fortement
le comportement
o  Mais est-ce différent des désirs de
récompenses qui ne sont pas considérés
comme irrésistibles ?
Anticipation de la récompense
Chez l’homme
ì  Passions / Golf
ì  Tango argentin
(Targhetta et al., J Behav Addict, in press)
ì  Supporteur de foot
Évolution
Alcoolisme est une maladie chronique et
récidivante que chez les malades
psychiatriques
Compton et al., Arch Gen Psychiatry 2007;64:566
Pickard H., AJOB Neurosci 2012;3:40
Efficacité d’une molécule ne définit pas une
« maladie »
ì  Décalage horaire
ì  Coupe-faim
ì  Mal des transports
ì  Dopage
Traitement
Efficacité des techniques non chimiques
Tenir compte en priorité des difficultés sociales, psychologiques,
relationnelles
Gestion des émotions négatives ; stratégies d’évitements
Management des contingences
« Stop and think »
Entretien motivationnel
Peterson T. Working with substance misusers:
a guide to theory and practic. Routeledge; London, UK: 2002
Risques de « médicalisation »
§ 
De-stigmatisation = absence du moindre sens de
responsabilité personnelle
§ 
Peut-on être responsable de sa « guérison » si on
n’est pas responsable de sa « maladie » ?
§ 
Médicaliser l’alcoolisme n’a pas permis
d’améliorer la prise en charge à l’échelon
individuel
Holden T., CMAJ 2012
Deux concepts opposés
o  Maladie neurologique incurable, génétiquement
favorisée, avec des compulsions irrésistibles,
fréquemment récidivante.
o  Utilisation secondaire d’alcool en réponse à des
troubles psychologiques, relationnels ou sociaux,
avec contrôle difficile mais qui peut être modifié
par apprentissage.
Addiction : maladie ou pas ?
Le débat doit reposer sur des évidences
scientifiques et des arguments rationnels et
non sur des mythes ou des positions
idéologiques
Stanbrook MB., CMAJ 2012;184:155