alcohol & adolescent brain development
TRANSCRIPT
ALCOHOL AND ADOLESCENT BRAIN DEVELOPMENT
Sandra A. Brown, Ph.D.University of California, San DiegoVeterans Health Service System
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