ALCOHOL AND ADOLESCENT BRAIN DEVELOPMENT

Sandra A. Brown, Ph.D.University of California, San DiegoVeterans Health Service System

Research

suppor

t

Adolescence in the Lifespan

Dahl,NYAS, 2002

Adolescence is the periodbetween the onset of puberty andthe attainment of adult roles and

responsibilities. Dahl, 2002

Fetus

Child

AdolescentYoung Adult

Middle Age

Senior

Adol

escent

Adolescent AUDs/SUDs Occur in the Context of Developmental Changes

• Biological (pubertal, neuroanatomical)

• Socioemotional (family/peer/intimate relations, emotional lability and management)

• Cognitive (information processing, executive functioning)

• Behavioral (risk taking, self-regulation)

Exposure to New and More Diverse Environments

0

5

10

15

20

25

30

35

40

45

50

8th 10th 12th

Grade

Pe

rce

nt

Us

ing

in P

as

t M

on

th

Alcohol

Cigarettes

Marijuana

Alcohol is the Drug of Choice Among Adolescents

Source: Monitoring the Future, 2003

Youth Drink Less Frequently than Adults, but Drink More Per Occasion

Source: SAMHSA National Survey on Drug Use and Health, 2002

4.79

2.67

4.87

8.91

0

1

2

3

4

5

6

7

8

9

10

Underage Adults

Drinks per Occasion Drinking Days per Month

(12-17) (26 and older)

Prevalence of Past-year DSM-IV Alcohol Dependence: United States, 2001-2002

0%

2%

4%

6%

8%

10%

12%

14%

18-2

021

-24

25-2

930

-34

35-3

940

-44

45-4

950

-54

55-5

960

-64

65-6

970

+

Grant, B.F. et al., Drug and Alcohol Dependence, in press 2004.Source: Grant BF et al. Drug Alcohol Depend. 2004. 74(3):223-34.

Alcohol and Youth

Alcohol Causes or Contributes to:

• Physical and sexual assault/high-risk sexual behavior

• Adverse effects on bones, liver, growth & reproductive function

• Academic problems and early dropout• Neurocognitive impairment and reduced

hippocampal volume

• Source: Brown, 2004

Disentangling Multiple Reciprocal Relations

Alcohol/Drugs

NeurocognitiveAbilities

Other AspectsOf Functioning

Neurobiological Studies of Alcohol Effects on Animals

Adolescent animals are:• Less sensitive to sedative effects of acute intoxication• More sensitive to disruption of memory, impairment of

neurotransmission in hippocampus and cortex, and social facilitation

Binge exposure produces long-lasting memory effects and damage to frontal-anterior cortical regions.

Prolonged ethanol exposure enhances withdrawal and produces changes in cortex and hippocampus.

Source: Spear & Varlinskaya, 2005

Brain Development

1st T

2nd T

3rd T

1 2 7 16 30

Prenatal Post-birth Age

Volume

RA

TE

OF

CH

AN

GE

Myelination

Synaptic Refinement

Metabolism

Blood Flow

Receptors

The Human Brain Continues to Develop into the Early 20s

>Increases in speed/efficiency >More regional specialization>Limbic region (emotions) matures earlier

than frontal lobes (planning, self-control, decision making)

Source: Geidd, 2004

Neurocognitive Impact of Alcohol on Youth

Middle Adolescence -Fewer Learning Strategies -Memory Impairment Late Adolescence -Attentional Decrement -Visuospatial Impairment Withdrawal May Impact Different Abilities than Use.

Neurocognitive Functioning of AUD and Community Teens

Brown, et al. (2000). Alcohol: Clin & Exp Res.

75%

80%

85%

90%

95%

100%

VerbalInformation

NonverbalInformation

Ret

enti

on R

ate

AlcoholDependent

NonabusingComparisons

•Gender•Age •Grade •SES•FH

•3 wks abstinent

10%10% 10%10%

Heavy drinking

Low Average High

Coping Skills

Light Drinking

High Attention

Average Attention

Low Attention

Tapert et al. (1999). Journal of Studies on Alcohol.

Neurocognition, Coping & Relapse

• Youth with poorer attention functioning who have poor coping skills are at very high relapse risk

Neuropsychological Functioning of Youth Four Years After Treatment

20

25

30

35

40

45

50

55

60

Treatment Four-Year Follow-Up

Timepoint

Vis

uo

sp

ati

al T

-sc

ore

Good treatmentoutcome

Post-txwithdrawal butNo recent use

Post-txwithdrawal andRecent use

Source: Tapert & Brown (1999). J Int Neuropsych Soc.

Alcohol and the Adolescent Brain

Neuropsychological Findings

Neuroimaging Research

•Planning/Executive Functioning

•Memory

•Visuospatial Skills

•Attention

•Reduced size of hippocampus

•Less brain response on memory tests

•Greater reactivity to alcohol cues

Neurodevelopmental Research Issues

• Development: biological and social

•Gender differences

•Family history of alcohol/substance

use disorder

•Psychiatric comorbidity

•Polysubstance use

•Abstinence duration

fMRI Task

SPATIAL WORKING MEMORY

VIGILANCE

FIXATION

FIXATION

7:48

++ +

VIGILANCETARGET TRIAL

TARGET TRIAL

+ + + +

SPATIAL WORKING MEMORY

TARGET TRIAL

+

Alcohol and Adolescents: Functional Magnetic Resonance Imaging (fMRI)

Adolescents (15-17 years old) with a history of heavy drinking show less BOLD response to challenging cognitive tasks than nondrinking peers.

GROUP T-TEST

STRONG INTENSITY

STRONG INTENSITY

Controls more

activated than AUD

AUD more activated

than Controls

AUD teens had less BOLD response while doing the spatial working memory in parietal and cingulate regions (p<.025).

side view

R L

Post-drinking effects predict much less activation

Regressions with N=24

(Control+AUD)p<.01

#Drinks predict more activation

#Drinks predict less activation

Post-Drinking Effects Predict Activation

Drinks per Month Predict Activation

Alcohol and Adolescents: Functional Magnetic Resonance Imaging (fMRI)

• 18-22 year olds with a history of alcohol dependence also show reduced brain activation.

• These youth also have a 10% lower performance on visuospatial memory tests.

Exposure to Alcohol Cues and Brain Reactivity: Adolescents

• Does the brain react differently to alcohol cues after youth have had alcohol experience?

• Does alcohol experience make a difference in likelihood to respond to alcohol advertisements?

YES !!!!!!

Cue Reactivity: Alcohol Dependent Adolescents vs. Controls

Non-Alcohol Pictures

++

Alcohol Pictures

+

+ +

Tapert et al. (2003). Arch Gen Psychiatry

-21 -13 -5

+3 +11 +19

Left Right

+27 +35 +43

+51 +59 +67

Tapert., Cheung, G. Brown, Frank, Paulus, Schweinsburg, Meloy, & S.A. Brown (2003).

fMRI Results of AUD and Control Adolescents During Alcohol Pictures Relative to Non-Alcohol Beverage Trials

Orange = AUD > Controls

Blue = Controls > AUD

Numbers = Axial Slice Position

Teen’s Brain Response

• Orange: AUD teens had more response to alcohol picturesTapert et al., 2003, Arch Gen Psychiatry

• Alcohol picture trials relative to non-alcohol beverage trials:

LEFT HEMISPHERE

Anterior cingulate & NAc

Orbital/prefrontal (BA11)

•Affect

•Interest

•Craving

Alcohol and the Adolescent Brain: What Do We Know?

1. Early involvement is associated with poorer behavioral measures of thinking abilities of youth.

-Memory and Learning Strategies

-Visuospatial Abilities and Attention

2. Continued heavy use leads to greater deterioration in cognitive functioning.

3. Early alcohol involvement is associated with under activation in several brain regions during cognitive tasks.

- Frontal and Prefrontal

- Parietal and Cingulate

4. Teens with alcohol experience are more reactive to alcohol cues/advertisements.

What Do We Need to Learn?

1. Are these deficits/brain changes permanent?

• How long do they last?

• Can we speed recovery?

2. To what extent are neurocognitive and neuroanatomical differences present before alcohol use starts?

3. Which children are most vulnerable to these adverse alcohol consequences?

The End