ken winters, ph.d. department of psychiatry university of minnesota [email protected] may 10, 2011...

Ken Winters, Ph.D.Department of PsychiatryUniversity of Minnesota

[email protected]

May 10, 2011Gainesville, FL

Adolescence, the Maturing Brain and Alcohol:

Intersections on the Developmental Highway

Adolescence is a Time-Limited Brain Disorder!

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

Center for AdolescentSubstance Abuse Research, University of Minnesota

1. Addiction as braindisease

2. Brain development

3. Alcohol susceptibility

4. Summary

5. Clinical opportunities

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).

Talks that are too technical can turn audiences into…

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

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

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

What about recovery?

Your Brain After Cocaine

Normal

Cocaine Addict - 10 days

Cocaine Addict - 100 days

Yellow = normal brain functioning

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

Cautions

• Brain imaging studies are based on small samples• gender, ethnic and cultural differences may

be significant.

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!

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?

Allstate ad, NY Times, May, 2007

An Immature Brain = Less Brakes on the “Go” System

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

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.

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

• 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

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

Impact of Peer Presence onRisky Driving in Simulated Context

Chein et al., in press

peer effect

• 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

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

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.

http://basis.typepad.com/.a/6a00d835805a6c69e20148c87cf477970c-popup

• Preference for ….




4. novelty

• Less than optimal..







An Immature Brain = Low Brain Power

Source: US News & World Report, 2005

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.

An Immature Brain = Absence of Judgment

Source: US News & World Report, 2005

• Taking risks is not always unhealthy.

• Growth experiences and extending one’s talents may involve risk-taking.



3. Drugsusceptibility

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.

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.

Evidence from epidemiological studies

Alcohol use starts early and peaks in the teen years

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+

%

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

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”

The Water Maze Test

Hidden

Slide courtesySion Kim Harris, Ph.D.

• Saline vs alcohol • Measures

-Swimming speed-Time to find platform


Adolescent rats are more sensitive to the

social disinhibition effects of alcohol. • greater social comfort from intoxication

Wanna lookfor some cheese

with me?Sure!


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.

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.


Alcohol may produce greater cognitive

disruptions in adolescents.

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

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

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

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

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

What’s Affected by Marijuana?

Adverse Effects

• Decreased coordination and reaction time• Impaired ability to concentrate• Impaired memory and learning ability

Teen Working Memory Performance

Source: Jacobsen et al. Impact of cannabis use on brain function in adolescents. Annals NY Acad Sci. 2004.




4. Summary

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

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)

Summary

Gray Matter Maturation(Gogtay et al., 2004)

reward incentives > perception of consequences

Summary

• Several lines of evidence suggesting that adolescents are more vulnerable to the effects of drugs – particularly alcohol – than adults.

• Why?

• Preference for...




4. novelty

• Less than optimal…







“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.

“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

DA

D2

Rec

epto

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vaila

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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



HeroinHeroin

MethMeth


controlcontrol addictedaddicted

“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?

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.




4. Summary

5. Clinical opportunities

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


• 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.

Your Brain After Cocaine

Normal

Cocaine Addict - 10 days after use

Cocaine Addict - 100 days after use

Yellow = normal brain functioning


• Discuss with teenagers the science of the neurobiology of addiction

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



HeroinHeroin

MethMeth


controlcontrol addictedaddicted


• Discuss the implications of using substances when the brain is still developing.

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


• Shape milieu to be teen-brain friendly:

• structure and rules• recreation• sensory activities and active learning• peer community• novelty


• Teach important skills not optimal for the teen brain

• impulse control

• “second” thought processes

• social decision making

• dealing with risk situations

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

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

• Taking risks is not always unhealthy.

• Growth experiences and extending one’s talents may involve risk-taking.

• Teen-brain friendly features of the 12-Step Model

• abstinence• novelty – new approach to life• structure• spiritual component• fellowship


• Two major treatment approaches seem accommodating to the teen brain:

• Cognitive – behavioral therapy (CBT)

• Motivational interviewing


Characteristics of CBT

• Focus on immediate, relevant and specific problems

• Solutions are realistic, concrete, specific

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

• 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

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

• 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

Hazelden’s Brain Development Curriculum for High School Science Classes

(eight 10-minute lessons)

School and community-based prevention programs

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

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.

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.

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.

Opportunities for Parents

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.

Recipe for a Healthy Brain

• Good diet• Vitamins (multi-vitamins)• Exercise• Sufficient sleep• Social connections• Learning music• Positive thinking• Helping others • New learning

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.

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

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….

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/

www.drugfree.org/Parent/

THANK YOU! [email protected]

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.

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

Contact

Ken Winters, [email protected]

Comments or Questions?

ken winters, ph.d. department of psychiatry university of minnesota [email protected] may 10, 2011...

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