ken winters, ph.d. department of psychiatry university of minnesota [email protected] may 10, 2011...
TRANSCRIPT
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Ken Winters, Ph.D.Department of PsychiatryUniversity of Minnesota
May 10, 2011Gainesville, FL
Adolescence, the Maturing Brain and Alcohol:
Intersections on the Developmental Highway
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Adolescence is a Time-Limited Brain Disorder!
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Support for this work was provided by the Archie and Bertha Walker Foundation, RKMC Private Foundation, and the Mentor Foundation.
The author expresses gratitude to these colleagues whose work and consultation significantly contributed to the development of this presentation:
Jay Giedd, National Institute on Mental Health (USA)Jeff Lee, Mentor Foundation (UK)Tom McLellan, Treatment Research Institute (USA)Linda Spear, SUNY at Binghamton (USA)Susan Tapert, University of California – San Diego (USA)
Acknowledgements
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Center for AdolescentSubstance Abuse Research, University of Minnesota
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1. Addiction as braindisease
2. Brain development
3. Alcohol susceptibility
4. Summary
5. Clinical opportunities
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Emerging Science:Brain Imaging
New insights because:
• 1990’s information explosion due to the development of brain imaging techniques (e.g., CT, PET and MRI).
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Talks that are too technical can turn audiences into…
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1. Addiction as braindisease
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Dopamine Neurotransmission
VTA/SNVTA/SNnucleus accumbensnucleus accumbens
frontalcortexfrontalcortex 00
100100200200300300400400500500600600700700800800900900
1000100011001100
00 11 22 33 44 5 hr5 hr
Time After AmphetamineTime After Amphetamine
% o
f B
as
al
Re
lea
se
% o
f B
as
al
Re
lea
se
AMPHETAMINEAMPHETAMINE
00
5050
100100
150150
200200
00 6060 120120 180180Time (min)Time (min)
% o
f B
asal
Re
lea
se%
of
Bas
al R
ele
ase
EmptyEmptyBoxBox FeedingFeeding
Di Chiara et al.Di Chiara et al.
FOODFOOD
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Your Brain on CocainePET scan
1-2 Min 3-4 5-6
6-7 7-8 8-9
9-10 10-20 20-30
Yellow = cocaine is binding or attaching itself to areas of the brain
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DA
D2
Rec
epto
r A
vaila
bili
tyD
A D
2 R
ecep
tor
Ava
ilab
ility
CocaineCocaine
AlcoholAlcohol
DA
DA
DA
DA DA DA
DA
Reward Circuits
DA DA DA DA
DA
Reward Circuits
DA
DA
DA
DA DA
DA
Drug AbuserDrug Abuser
Non-Drug AbuserNon-Drug Abuser
HeroinHeroin
MethMeth
Dopamine D2 Receptors are Lower in Addiction
control addicted
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What about recovery?
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Your Brain After Cocaine
Normal
Cocaine Addict - 10 days
Cocaine Addict - 100 days
Yellow = normal brain functioning
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Partial Recovery of Brain Dopamine Transportersin Methamphetamine (METH)
Abuser After Protracted Abstinence
Normal Control METH Abuser(1 month detox)
METH Abuser(24 months detox)
0
3
ml/gm
Source: Volkow, ND et al., Journal of Neuroscience 21, 9414-9418, 2001.
ADDICTION CAN BE TREATED
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1. Addiction as braindisease
2. Brain development
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Cautions
• Brain imaging studies are based on small samples• gender, ethnic and cultural differences may
be significant.
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Adolescence is a period of profound brain maturation.
We thought brain
development was complete
by adolescence
We now know… maturation
is not complete until about
age 25!
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Important ages of majority and privileges
16 - emancipation
- driving
18 - gambling (usually age 21 when alcohol served)
- smoking (some at age 19
- military
21 -drinking
What one “privilege” in our culture does not become fully availableuntil the age of 25?
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Allstate ad, NY Times, May, 2007
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An Immature Brain = Less Brakes on the “Go” System
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Brain Development
1 2 7 16 30
Prenatal Post-birth Age
RA
TE
OF
CH
AN
GE
Volume
Metabolism
Blood Flow
Receptors
Tapert & Schweinsburg (2005)
Adolescence
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Brain Weight by Age
Source: Dekaban, A.S. and Sadowsky, D. Annals of Neurology, 4:345-356, 1978
New
born
FemalesMalesI’m adult-size now!
AgeSlide courtesySion Kim Harris, Ph.D.
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Brain Development
1 2 7 16 30
Prenatal Post-birth Age
RA
TE
OF
CH
AN
GE
Myelination
Synaptic Refinement
Volume
Metabolism
Blood Flow
Receptors
Tapert & Schweinsburg (2005)
Adolescence
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• When the pruning is complete, the brain is faster and more efficient.
• But… during the pruning process, the brain is not functioning at full capacity.
Construction Ahead
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Maturation Occurs from Back to Front of the BrainImages of Brain Development in Healthy Youth
(Ages 5 – 20)
Source: PHAS USA 2004 May 25; 101(21): 8174-8179. Epub 2004 May 17.
Blue represents maturing of brain areas
Earlier development: Motor Coordination Emotion Motivation
Later development: Judgment
Process: Promotes puberty
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Impact of Peer Presence onRisky Driving in Simulated Context
Chein et al., in press
peer effect
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• Preference for…
1. physical activity
2. high excitement and rewarding activities
3. activities with peers that trigger high intensity/arousal
4. novelty
• Less than optimal…
5. control of emotional arousal
6. consideration of negative conseq.
• Greater tendency to…
7. be attentive to social information
8. take risks and show impulsiveness
Implications of Brain Development for Adolescent Behavior
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Risk-Taking
• Based on science of brain development, a modern view of risk taking in adolescence is…• normative; important to development
• evolutionarily adaptive
• is due primarily to emotional and contextual, not cognitive, factors
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Childhood Self-control as a Predictor of Adult Substance Use Dependence (Moffitt et al., in press)
Outcomes were converted to Z-Scores and childhood self-control is represented in quintiles.
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• Preference for ….
1. physical activity
2. high excitement and rewarding activities
3. activities with peers that trigger high intensity/arousal
4. novelty
• Less than optimal..
5. control of emotional arousal
6. consideration of negative conseq.
• Greater tendency to…
7. be attentive to social information
8. take risks and show impulsiveness
Implications of Brain Development for Adolescent Behavior
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An Immature Brain = Low Brain Power
Source: US News & World Report, 2005
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MHT IQ age 11 years
40 60 80 100 120 140
MH
T I
Q a
ge
80
yea
rs
40
60
80
100
120
140
Taking the Same Ability Test at Age 11 & Age 80:Scottish Mental Survey 1932
Deary et al. (2004) Journal of Personality and Social Psychology, 86, 130-147.
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An Immature Brain = Absence of Judgment
Source: US News & World Report, 2005
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• Taking risks is not always unhealthy.
• Growth experiences and extending one’s talents may involve risk-taking.
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1. Addiction as braindisease
2. Brain development
3. Drugsusceptibility
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Adolescents may be more susceptible than adults to alcohol
(acknowledgement to Linda Spear, Ph.D.)
Implications of Brain Development for Drug Abuse Vulnerability
Unethical to give human adolescents alcohol in the laboratory;much of the best evidence comes from adolescent rat studies.
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Cautions
• Supporting evidence on alcohol sensitivity from animal models needs to be interpreted with prudence. • assumptions of commonality across species pertaining
to...• key characteristics of the adolescent developmental stage• acute effects of intoxication
• lab rats are administered ethanol via injection or directly into the stomach
• stress - impacts absorption and behavioral effects
• Other developmental factors, such as hormonal changes, are also biomedical contributors to alcohol sensitivity.
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Evidence from epidemiological studies
Alcohol use starts early and peaks in the teen years
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Prevalence of Past-Year DSM-IV Alcohol Dependence: United States, 2001-2002
(Grant, B.F., et al., Drug and Alcohol Dependence, 74, 223-234, 2004)
12.211
5.8
4.1 3.9 3.8 3.7
1.9
0.3 0.20
2
4
6
8
10
12
14
15-20 21-24 25-29 30-34 35-39 40-44 45-49 50-54 55-59 60+
%
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Percentages of Past Year Alcohol Use Disorder (Abuse or Dependence) Among Adults Aged 21 or Older, by Age of First
Use (SAMHSA, 2005)
1615
9
4.22.6
0
5
10
15
20
<12 yrs 12-14 yrs 15-17 yrs 18-20 yrs 21+ yrs
Age Started Drinking
%
Fewer Problems in ThoseWho Start Later
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Are adolescents more susceptible to alcohol than adults?
Comparing adolescent and adult rats, bothhaving no prior exposure to alcohol and matched on temperament…
Adolescent rats are less sensitive to the
sedative and motor impairment effects of
intoxication.• more drinking before “signals to stop”
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The Water Maze Test
Hidden
Slide courtesySion Kim Harris, Ph.D.
• Saline vs alcohol • Measures
-Swimming speed-Time to find platform
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Are adolescents more susceptible to alcohol than adults?
Adolescent rats are more sensitive to the
social disinhibition effects of alcohol. • greater social comfort from intoxication
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Wanna lookfor some cheese
with me?Sure!
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Are adolescents more susceptible to alcohol than adults?
Adolescent rats are less sensitive to the sedative
and motor impairment effects of intoxication.
Adolescent rats are more sensitive to the social
disinhibition effects of alcohol.
#2 and #3: May contribute to binge drinking and increased risk to alcohol dependence.
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Binge Alcohol Use in the Past Month by Age Group(SAMHSA, 2005)
11.16
41.2
21.1
0
10
20
30
40
12-17 years 18-25 years 26+ years
perc
en
t b
ing
e u
se p
ast
mon
th
Binge = 5+ drinks same occasion on at least one day in the past 30 days.
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Are adolescents more susceptible to alcohol than adults?
Alcohol may produce greater cognitive
disruptions in adolescents.
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Human Data: Alcohol’s Effectson Memory
Adolescent rats more sensitive to…
• disruption in memory
• impairment of neurotransmission in hippocampus and cortex
Where ismy cheese?
Source: Spear, 2002
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Human Data: Alcohol’s Effects
8687
9796
70
75
80
85
90
95
100
Alc Dep
Non-AlcDep
Verbalinformation
Nonverbalinformation
Rete
nti
on
Rate
%
Source: Brown et al., 2000
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Human Data: Alcohol’s Effectson the Hippocampus
Adolescents with a history of alcohol
use disorder…
Hippocampus volume (10%)
Source: Tapert & Schweinsburg, 2005
Where is myiPod?
Hippocampus converts information to memory
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hippocampus
MRI: Hippocampal Size
Nagel, Schweinsburg, Pham, & Tapert, 2005
• __________
– ______ ___ ____
– ___ _______ __ _____ _
– __ __ ____________ ____ _________ ___________ ___ __ ____ ______ _______ _____ ____ ____ __ __ ______
• __________
– ______ ___ ____
– ___ _______ __ _____ _
– __ __ ____________ ____ _________ ___________ ___ __ ____ ______ _______ _____ ____ ____ __ __ ______
• Hippocampus
– Encodes new info
– Left smaller in AUD teens (p<.01)
– But no relationship with cognitive functioning (due to less severe alcohol group than Brown et al. sample?)
• Hippocampus
– Encodes new info
– Left smaller in AUD teens (p<.01)
– But no relationship with cognitive functioning (due to less severe alcohol group than Brown et al. sample?)
10% smaller volume
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Teen Drinking & Brain Activation
Non-Drinkers Heavy Drinkers
Act
ivat
ion
De-
acti
vati
on
Age 16
Age 20
Tapert et al., 2001, 2004Slide courtesy of Susan Tapert, PhD.
2 yrs
drinking
5 yrs
drinking
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What’s Affected by Marijuana?
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Adverse Effects
• Decreased coordination and reaction time• Impaired ability to concentrate• Impaired memory and learning ability
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Teen Working Memory Performance
Source: Jacobsen et al. Impact of cannabis use on brain function in adolescents. Annals NY Acad Sci. 2004.
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1. Addiction as braindisease
2. Brain development
3. Alcohol susceptibility
4. Summary
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Summary • Adolescence is an extended period of
transition from reliance on adults to independence
• Normal adolescence is characterized by….• increase in conflicts with family members• desire to be with one’s friends• resistance to messages from authority• irritability• risk taking• proclamations of sheer boredom
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Summary
• The brain undergoes a considerable amount of development during the teen years.
• The last area to mature is the prefrontal cortex region; involved in planning, decision making and impulse control.
Gray Matter Maturation(Gogtay et al., 2004)
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Summary
Gray Matter Maturation(Gogtay et al., 2004)
reward incentives > perception of consequences
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Summary
• Several lines of evidence suggesting that adolescents are more vulnerable to the effects of drugs – particularly alcohol – than adults.
• Why?
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• Preference for...
1. physical activity
2. high excitement and rewarding activities
3. activities with peers that trigger high intensity/arousal
4. novelty
• Less than optimal…
5. control of emotional arousal
6. consideration of negative conseq.
• Greater tendency to…
7. be attentive to social information
8. take risks and show impulsiveness
Implications of Brain Development for Adolescent Behavior
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“Dopamine Sensitivity” Theory
• The developing brain has a robust dopamine system• Drugs may be more reinforcing
to the developing brain and thus, more subjected to the hijacking process.
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“Dopamine Sensitivity” Theory
• Dopamine is a key neurotransmitter in the brain’s reward pathway system.• Dopamine is a key brain chemical that regulates our mood
• Drugs “hijack” our dopamine activity
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DA
D2
Rec
epto
r A
vaila
bili
tyD
A D
2 R
ecep
tor
Ava
ilab
ility
CocaineCocaine
AlcoholAlcohol
DA
DA
DA
DA DA DA
DA
Reward Circuits
DA DA DA DA
DA
Reward Circuits
DA
DA
DA
DA DA
DA
Drug AbuserDrug Abuser
Non-Drug AbuserNon-Drug Abuser
HeroinHeroin
MethMeth
Dopamine D2 Receptors are Lower in Addiction
controlcontrol addictedaddicted
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“Priming the Pump” Theory
• Does early exposure to drugs alter the brain in ways that contribute to the addiction process in ways that are unique to youth?
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Average Number of Self-Administered Doses of NicotineWhen Rats Were Adults (Levin et al., 2003)
10
4.5
0
2
4
6
8
10
12
Adolescent Adult
Average # self-admin.
Age of Rates When First Exposed to Nicotine. All DataCollected When Rats were Adults.
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1. Addiction as braindisease
2. Brain development
3. Alcohol susceptibility
4. Summary
5. Clinical opportunities
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Brain Development: Opportunities for Treatment
• Treatment is vital.• Youth is a particularly vulnerable period for
developing a substance use disorder.
• Not treating it during youth…• probably increases the likelihood that the adolescent
will have a drug problem as an adult • may contribute to learning and memory problems
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Brain Development: Opportunities for Treatment
• Sobriety is vital.• All addicted brains need to be drug-free so that
neurological repair can occur.
• Restoration may be even more critical for youth due to concerns of drug toxicity on the developing brain.
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Your Brain After Cocaine
Normal
Cocaine Addict - 10 days after use
Cocaine Addict - 100 days after use
Yellow = normal brain functioning
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Brain Development: Opportunities for Treatment
• Discuss with teenagers the science of the neurobiology of addiction
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DA
D2
Rec
epto
r A
vaila
bili
tyD
A D
2 R
ecep
tor
Ava
ilab
ility
CocaineCocaine
AlcoholAlcohol
DA
DA
DA
DA DA DA
DA
Reward Circuits
DA DA DA DA
DA
Reward Circuits
DA
DA
DA
DA DA
DA
Drug AbuserDrug Abuser
Non-Drug AbuserNon-Drug Abuser
HeroinHeroin
MethMeth
Dopamine D2 Receptors are Lower in Addiction
controlcontrol addictedaddicted
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Brain Development: Opportunities for Treatment
• Discuss the implications of using substances when the brain is still developing.
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Memory Effects
8687
9796
70
75
80
85
90
95
100
Alc Dep
Non-AlcDep
Verbalinformation
Nonverbalinformation
Rete
nti
on
Rate
%
Source: Brown et al., 2000
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Brain Development: Opportunities for Treatment
• Shape milieu to be teen-brain friendly:
• structure and rules• recreation• sensory activities and active learning• peer community• novelty
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Brain Development: Opportunities for Treatment
• Teach important skills not optimal for the teen brain
• impulse control
• “second” thought processes
• social decision making
• dealing with risk situations
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Challenges and Risk for Relapse
• Nearly half of youth who relapse…• did not expect substances to be in
the situation
• did not think about using beforehand
• were with new friends.
Brown et al., 1990
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Brain Development: Implications for Treatment
• Teach important skills not optimal for the teen brain
• impulse control
• “second” thought processes
• social decision making
• dealing with risk situations
• taking healthy risks
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• Taking risks is not always unhealthy.
• Growth experiences and extending one’s talents may involve risk-taking.
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• Teen-brain friendly features of the 12-Step Model
• abstinence• novelty – new approach to life• structure• spiritual component• fellowship
Brain Development: Opportunities for Treatment
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• Two major treatment approaches seem accommodating to the teen brain:
• Cognitive – behavioral therapy (CBT)
• Motivational interviewing
Brain Development: Opportunities for Treatment
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Characteristics of CBT
• Focus on immediate, relevant and specific problems
• Solutions are realistic, concrete, specific
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Characteristics of Motivational Interviewing
• De-emphasize labels• Emphasis on personal choice and
responsibility• Therapist focuses on eliciting the
client's own concerns• Resistance is met with reflection and
non-argumentation• Treatment goals are negotiated; client’s
involvement is seen as vital
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• Because many teens begin using substances at a young age and because of their possible deleterious effects on the developing brain, the urgency for prevention is real.
Opportunities for Drug Prevention
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1. Delaying the onset of drug use, especially if it is delayed until adulthood, is better for both brain development and probably reduces future risk for addiction.
2. Drug abuse may contribute to learning deficits.
3. Drug use increases risk of other harms (social, legal, etc.)?
Drug Prevention Messages for Youth
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• There are now some age-appropriate resources to educate youth about their developing brain.
• Our research group has developed a classroom presentation for students; e-mail me: [email protected]
• New resource from www.BSCS.org Drug Abuse, Addiction and the Adolescent Brain
• Hazelden will be publishing a resource in 2010 for students (www.hazelden.org)
Classroom Resources
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Hazelden’s Brain Development Curriculum for High School Science Classes
(eight 10-minute lessons)
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School and community-based prevention programs
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These programs accommodate the youthful brain by…
• Providing novelty
• Including peer influence • Including active learning and
sensory activities
• Providing adult supervision and other situational controls
Many evidenced-based prevention programs are teen-brain friendly
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Selected Examples of Prevention ProgramsMeeting Rigorous Outcome Criteria
www.nrepp.samhsa.gov
• Raising Healthy Children[Catalano et al. (2003); Brown, Catalano, Fleming, Haggerty, & Abbott (2005); depts.washington.edu/sdrg]
• Nurse-Family Partnership Program (NFP)[Olds et al. (1998); www.nursefamilypartnership.org]
• The Incredible Years[Reid, Webster-Stratton, & Beauchaine (2002); Webster-Stratton & Taylor (2001); www.incredibleyears.com]
• Triple P-Positive Parenting(Heinrichs et al. (2006); Sanders, Markie-Dadds, Tully, & Bor (2000); www.triplep.net ]
• Family Matters[Bauman et al. (2000); Bauman et al. (2002); http://familymatters.sph.unc.edu/index.htm]
• Families That Care: Guiding Good Choices [Park et al. (2000); Spoth et al. (2004); http://www.dsgonline.com/mpg]
Source: Spoth, R., Greenberg, M., & Turrisi, R. (2008). Preventive interventions addressing underage drinking: State of the evidence and steps toward public health impact. Pediatrics, 121, 311-336.
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1. Curriculum organized around risk and protective factors and processes that contribute, promote or cause drug use behaviors.
2. Assume the validity of the “gateway hypothesis” and focus on preventing the onset of alcohol and tobacco use.
3. Take a multidimensional approach.
4. Program curriculum spans multiple grades and extends several developmental periods
5. Activities and curriculum are developmentally and culturally adjusted.
Elements of Effective Prevention Programs (Winters, Fawkes et al., 2007)
Source: Winters, K.C., Fawkes, T., Fahnhorst, T., Botzet, A., & August, G.J. (2007). A synthesis review of exemplary drug abuse prevention programs in the United States. Journal of Substance Abuse Treatment, 32, 371-380.
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6. Programs expend great deal of resources and effort in youth and family engagement.
7. Youth component focuses on building social skills. 8. Parent component focuses on discipline and support
parenting behaviors. 9. Program structure enlists broad-based involvement in
decision making, including ongoing opportunities by stakeholders to refine and shape the program.
10. Several aspects of the program are infused with features that promote its sustainability.
Elements of Effective Prevention Programs (Winters, Fawkes et al., 2007)
Source: Winters, K.C., Fawkes, T., Fahnhorst, T., Botzet, A., & August, G.J. (2007). A synthesis review of exemplary drug abuse prevention programs in the United States. Journal of Substance Abuse Treatment, 32, 371-380.
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Opportunities for Parents
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Working with Parents
P = Promote activities that capitalize on the strengths of the developing brain.
A = Assist children with challenges that require planning.
R = Reinforce their seeking advice from adults; teach decision making.
E = Encourage lifestyle that promotes good brain development.
N = Never underestimate the effects of drugs on the developing brain;
emphasize the importance of drug-free lifestyle.
T = Tolerate the “oops” behaviors due to an immature brain.
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Recipe for a Healthy Brain
• Good diet• Vitamins (multi-vitamins)• Exercise• Sufficient sleep• Social connections• Learning music• Positive thinking• Helping others • New learning
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Working with Parents
P = Promote activities that capitalize on the strengths of the developing brain.
A = Assist children with challenges that require planning.
R = Reinforce their seeking advice from adults; teach decision making.
E = Encourage lifestyle that promotes good brain development.
N = Never underestimate the effects of drugs on the developing brain;
emphasize the importance of drug-free lifestyle.
T = Tolerate the “oops” behaviors due to an immature brain.
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1. Examine (and adjust if necessary) your own behavior and attitude concerning drugs
2. Have family talks about the issues of drug use3. Have clear rules about what is expected in your
teenager4. Monitor your child’s adherence to the rules; apply
rewards and consequences5. Provide opportunities for healthy and positive
activities
Action Steps to Improve Likelihood of Raising a Drug Free Child
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1. Reasoning with your child
2. Educational-only programs
3. Pledges not to engage in risky behavior
Remind parents: Do not expect much impact from….
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Parent programs
• Our research group has developed a parent presentation; e-mail me: [email protected]
• Mentor Foundation’s Prevention Smart Parents
www.mentorfoundation.org
• New web-based resources from Partnership for a Drug-Free America
www.drugfree.org/Parent/
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www.drugfree.org/Parent/
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THANK YOU! [email protected]
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Suggested Readings
Dahl, R.E. & Spear, L.P. (Eds.) (2004). Adolescent brain development: vulnerabilities and opportunities. NY, NY: Annals of the New York Academy of Sciences, Volume 1021.
Dubuc, B. (n.d.). The brain from top to bottom. Retrieved September 1, 2004, from McGill University Web site: http://www.thebrain.mcgill.ca/flash/index_d.html#
Nestler, E. J., & Malenka, R. C. (2004, March). The addicted brain. Scientific American, 290 (3), 78-85.
Wallis, C. (2004, May 10). What makes teens tick? Time, 163, 57-65.
U.S. News & World Report. (Special Issue, 2005). Mysteries of the teen years. Author.
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Brown, S.A., Tapert, S.F., Granholm, E., & Delis, D.C. (2000). Neurocognitive functioning of adolescents: Effects of protracted alcohol use. Alcoholism: Clinical and Experimental Research, 242, 164-171.
Deary et al. (2004). Journal of Personality and Social Psychology, 86, 130-147.Giedd. J. N. (2004). Structural magnetic resonance imaging of the adolescent brain. Annals of the New
York Academy of Sciences, 1021, 77-85.Gogtay, N., Giedd, J.N., et al. (2004). Dynamic mapping of human cortical development during
childhood through early adulthood. Proceedings of the National Academy of Sciences, 101 (21), 8174 – 8179.
Grant, B.F., Dawson, D., et al. (2004). The 12-month prevalence and trends in DSM-IV alcohol abuse and dependence: United States, 1991-1992 and 2001-2002. Drug and Alcohol Dependence, 74, 223-234.
Nagel, B.J., Schweinsburg, A.D., Phan, V., & Tapert, S.F. (2005). Reduced hippocampal volume among adolescents with alcohol use disorders without psychiatric comorbidity. Neuroimaging, 139, 181 –190.
Spear, L. P. (2002). Alcohol’s effects on adolescents. Alcohol Health and Research World, 26(4), 287-291.
Tapert, S. & Schweinsburg, A.D. (2005). The human adolescent brain and alcohol use disorders (pp 177-197). In M. Galanter (Ed.), Recent developments in alcoholism: Vol XVII. Washington D.C.: American Psychiatric Press.
Winters, K.C., & Lee, S. (2008). Likelihood of developing an alcohol and cannabis use disorder during youth: Association with recent use and age. Drug and Alcohol Dependence, 92, 239-247.
References