Transcript 2-Gilberto Gerra

Addiction as a multi-factorial disease:
early evidence-based prevention
Gilberto Gerra
GLOBAL CHALLENGES SECTION
Human Security Branch
Division for Operations
SUBSTANCE ABUSE
A social problem?
A moral problem?
An educational problem?
A cultural problem?
does not need evidence-based interventions
no serious evaluation can be done
uncoordinated initiatives are acceptable
'addiction treatments'
as rhetoric masquerading
as medicine. . .
… to place responsibility
for excessive drug-taking
where it is usually absent
in public discourse:
on the individual drug-user
(2000)
On marginalized children?
On abused children?
On emotionally
neglected children?
On socially deprived adolescents?
WHO, 2004
Substance dependence is
as much a disorder of the brain
as any other psychiatric illness
mRNA level
peptides
proteomics
Substance-induced
neurochemistry
(predictable after
behaviors
chronic exposure)
Genetic
(25-70%)
DNA
SNPs
Other
polymorphisms
Kreek et al., 2004, NeuroMolecular Medicine
Environmental
(very high)
Prenatal
Postnatal
Contemporary
Cues
prolonged alcohol ingestion leads to neuronal loss
Ruela et al., 1994
Abstinent
cocaine addicts
The effects of
verbal cues:
words related
with cocaine
Venneri and Gardini, 2007
Abstinent
heroin addicts
The effects of
verbal cues:
words related
with heroin
Venneri and Gardini, 2007
Healthy
control subjects
who never used
illicit drugs
The effects of
verbal cues:
words related
with cocaine and
heroin
Venneri and Gardini, 2007
MEASURES TO PREVENT
DRUG USE DISORDERS
- DISSEMINATING INFORMATION
- INCREASING RISK PERCEPTION
- RAISING AWARENESS
- STRENGTHENING PEER PRESSURE RESISTENCE
- REDUCING SUPPLY
Gene variants
influencing
temperament
and personality
traits
Impaired
parents attachment
Difficult
temperament
Problematic
behavior
Reduced
bonding to family
Reduced engagement
in school
LL
SL
SS
Abstinent
37,73%*
50,54%
11,83%
Experimenters
23,19%
50,72%
26,09% *
=7.13 p<0.005
LL
SL
SS
NOVELTY SEEKING
15,72
19,41
21,75*
BDHI DIRECT AGGRESSION
51,03
55,70
59,58*
LL
SL
SS
smokers
26.53%
50.00%
23.47%
neversmoking
subjects
37.63%
52.69%
9.68% *
* chi2=7.33, p<0.05
gene variants that alter levels
of DAT expression provide
the best current candidate mechanism
for reported associations between
DAT gene markers, ADHD and
other more tentatively associated
neuropsychiatric disorders
Vandenbergh et al., 2000
American Journal of Medical Genetics Part B (Neuropsychiatric Genetics) 141B:1–7 (2007)
_____________________________________________________________________________
Perceived Parenting Behavior in the Childhood of
Cocaine Users: Relationship With Genotype and
Personality Traits
G. Gerra,1* A. Zaimovic,1 L. Garofano,2 F. Ciusa,1 G. Moi,1 P. Avanzini,3 E. Talarico,3 F. Gardini,4 F.
Brambilla,1 M. Manfredini,5 and C. Donnini5
1Centro Studi Farmaco-tossicodipendenze, Ser.T., AUSL, Parma, Italy
2Reparto Investigazioni Scientifiche (RIS), Carabinieri di Parma, Parma, Italy
3Servizio Immuno-trasfusionale, Azienda Universita`-Ospedale di Parma, Italy
4Dipartimento di Medicina Interna, Azienda Universita`-Ospedale di Parma, Italy
5Dipartimento di Genetica Antropologia Evoluzione, Universita` degli Studi di Parma, Parma, Italy
Perceived parenting behaviour in the childhood of cocaine users:
relationship with genotype and personality traits (Gerra et al., 2007
PBI
Paternal care
PBI
Maternal care
BDHI
Direct
aggression
25,490,42
27,590,38
45.32.9
cocaine users
LL-SL 5-HTT
genotypes
22,560.9
24.610.5
59.32.9
cocaine users
SS 5-HTT
genotypes
18.780.4
18.890.45
63.252.5
abstinent
subjects
Nilsson et al., 2005
adolescents with the S allele of the 5-HTT gene
and with family relations being "neutral"
or "bad" had a 12- to 14-fold increased risk
for high alcohol intoxication frequency
aggressive
behavioural
under-control
noveltysensation
seeking
harm avoidant
behavioural control
submissive
MEASURES TO PREVENT
DRUG USE DISORDERS
Dealing with difficult temperaments
and personality traits
Training for parents
Strengthening family program
Training for teachers
Personalized educational plans
School/Family efforts integration
Support to families
prenatal stress induces
permanent alterations
in dopaminergic activity
and in cerebral asymmetry
increase in reactivity to anxiety-provoking
situations in pre-natally stressed offspring
Fride and Weinstock, 1988
prenatal stress induces
long-lasting changes
in the dopamine sensitivity
of the nucleus accumbens
and in the capacity to develop
amphetamine-induced sensitization
in adulthood
Henry et al., 1995
European Journal of Pharmacology, 2004
Morley-Fletcher S., Puopolo M.,
Gentili S., Gerra G., Macchia T.
and Laviola G.
5
Slips
Number of Slips
4
2
3
2
1
0
1
0
0
2
15
60
120
180
8
3
Inactivity
Episodes of Inactivity
Prenatal stress affects
3,4-methylenedioxy
methamphetamine
pharmacokinetics
and drug induced
motor alterations in
adolescents female rats
3
6
**
4
2
0
1
0
0
15
60
120
180
Psychopharmacology, Huot et al., 2001
Rat pups
- normal animal facility rearing
- 15 min of maternal separation (postnatal days 2-14)
- 180 min of maternal separation (postnatal days 2-14)
------------------------------------------------------------------------------------------------------------
“180 min. rats”:
- an elevation in ACTH and CORTISOL responses
- less time in the open arms – elevated plus maze (anxiety)
- drank less of a water-sucrose solution
- drank more of an ethanol-sucrose solution
Monkeys who suffer maternal deprivation in childhood
tend to be fearful, more aggressive, less exploratory,
and subject to binge drinking on exposure to alcohol
Reduced serotonin transporter
Ichise et al., 2006
Variables
Age
Coeff.
p-value
-.076
.366
-3.088
.001
Antipathy father (ref. <30)
.284
.794
Neglect mother (ref. <25)
-1.836
.049
Neglect father (ref. <26)
-1.740
.125
Antipathy mother (ref. <28)
R2
.263
DOPAMINE SYSTEM AND NEGLECT
Childhood adversity, poly-substance use, and disordered eating
in adolescent Latinas: mediated and indirect paths
in a community sample.
Hodson et al., 2006
Physical/emotional abuse predicted
poly-substance use and weight concerns,
and these associations were mediated
by impaired current attachment.
Stress (adverse childhood experiences)
as a mediating factor in the association between
the DRD2 TaqI polymorphism and alcoholism
DRD2 GENE,
STRESS AND
ALCOHOLISM
Madrid et al., 2001
J Psychosoc Nurs Ment Health Serv.
Social isolation and sexual abuse among women who smoke crack.
Young et al., 2001
social isolation
sexually abused
women
substance abuse
low childhood socio-economic status
was associated with an increased risk
of substance dependence
(tobacco, alcohol, drugs)
and poor physical health
cardiovascular risk
in adulthood
Melchior et al., 2007
MEASURES TO PREVENT
DRUG USE DISORDERS
Protect children from adverse social experiences
Laws and norms to protect pregnancy
Laws and norms to protect early childhood
Strengthening family program for families at risk
Economic support to family
Life skills programs in school
Selected-indicated prevention
Alleviate poverty and social exclusion
Community empowerment
J Abnorm Child Psychol.
Conduct problems, depressive symptomatology
and their co-occurring presentation in childhood
as predictors of adjustment in early adolescence
- lower academic adjustment
- lower social competence
- risk for substance use disorders
Ingoldsby et al., 2006
Arch Gen Psychiatry
Prospective effects of attention-deficit/hyperactivity disorder,
conduct disorder, and sex on adolescent substance use and abuse.
Elkins et al., 2007
Hyperactivity/impulsivity predicts
later substance problems,
even after growth in later-emerging CD
is considered
Inattention alone poses less risk
Dev Psychopathol.
Course and outcome of bipolar spectrum disorder
in children and adolescents: a review of the existing literature.
Birmaher and Axelson, 2006
Bipolar Disorder in children and adolescents
is associated with high rates of:
hospitalizations,
psychosis,
suicidal behaviors,
substance abuse,
family and legal problems,
as well as poor psychosocial functioning
MEASURES TO PREVENT
DRUG USE DISORDERS
- The involvement of childhood
neuropsychiatry not for
children medicalization, but
for support to parents and teachers
- Early screening of sub-clinical disorders
- Early family therapy and behavioural therapy
Taking into account:
- Subgroups of individuals (special population)
- Social-ethnical-environmental differences
Standard evaluation per se may present
very consistent limitations
The spectrum of substance use disorders
Adolescent at risk
Minimal experimenter
Experimenter
Chronic user
Abuser
Dependent
Severely dependent
Policy-Program
Evaluation
Concomitant
psychiatric disorders
Prevention – National Responses
Prevention
50%
40%
30%
20%
10%
0%
Prevention All
Measures
Information
Lifeskills
Alternatives
Approaches
1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
Effects size
inform
L.
P. family
skills skills
FAMILY BASED PREVENTION PROGRAMS
A benefit-cost ratio of $9.60
per $1 invested
SCHOOL BASED PREVENTION PROGRAMS
A benefit-cost ratio of $4.25
per $1 invested