Neuroimaging Findings in Young Drinkers: Does Teenage Drinking Harm the Brain? Susan F. Tapert, Ph.D. University of California, San Diego

Neuroimaging Findings in Young Drinkers: Does Teenage Drinking Harm the Brain? Susan F. Tapert, Ph.D. University of California, San Diego

2 Overview What is normal adolescence? How do binge drinkers differ? Does the media have a role? Prevention implications

Past Month Use of Substances Monitoring the Future, 2013, ESPAD 2013 3

% Meeting Alcohol Use Disorder Criteria by Adulthood Age of First Drink 100 75 50 25 0 17 14 or Younger 10 4 3 15-17 18-20 21 or Older Age at First Drink National Household Drug Use & Health, 2010 4

Quick Brain Review! 5

6 Gray & White Matter Top view Side view

Tapert & Schweinsburg, 2005 7 Adolescent Brain Development Volume Metabolism Myelination Blood Flow Receptors Synaptic Refinement Adolescence RATE OF CHANGE 1 2 7 16 30 Prenatal Post-birth - Age

Volume (Cubic cm) Prefrontal Gray Matter Boys Peak Girls Peak Age Giedd et al., 1999, 2006; Lenroot & Giedd, 2010 8

Bava, Thayer, Jacobus, Ward, Jernigan, & Tapert, 2010, Brain Research 9 White Matter Change Right Frontal- Parietal +11% Frontal +8% Left Frontal- Parietal +5% R thalamic fibers +10% R posterior limb of internal capsule +5% Significant fiber improvement, age 17.5 to 19

Casey et al., 2008; Eaton et al., 2006; Galvan et al., 2006 10 Adolescent Brain Development 2-4x higher rate of death, crime, substance use Overactive limbic/subcortical + underdeveloped frontal lobe

11 Adolescent Binge Drinking What is normal adolescence? How do binge drinkers differ? Does the media have a role? Prevention implications

Retention Rate Brown, Tapert, Granholm, & Delis, 2000, ACER 12 Memory 100% 95% 90% Light Drinkers (n=24) Heavy Drinkers (n=33) 85% 80% 75% Verbal Info Nonverbal Info

T-score Tapert & Brown, 2000, Addictions 13 Attention 60 55 Light Drinkers (n=50) Heavy Drinkers (n=101) 50 45 Attention Speeded Info Processing

Longitudinal Study of Initiation Recruited from middle schools Followed annually: cognitive test, brain imaging, interviews Age 12-14 Age 15-18 Testing & Scans Non-Users N=296 R01 AA13419 (PI: Tapert) Follow up Testing &Scans Non-Users ~40% Heavy Users ~30% 14

Complex Figure Memory 15

Z-Score Change <-- Worse Better --> Initiation of Drinking: Females More drinks worse picture memory 4 3 2 1 0-5 5 15 25-1 -2-3 -4 Drinks Per Month Squeglia et al., 2009, Psychol Add Beh 16

Digit Vigilance 17

Squeglia et al., 2009, Psychol Add Beh Z-Score Change <-- Worse Better --> 18 Initiation of Drinking: Males More hangovers worse attention 3 2,5 2 1,5 1 0,5 0-0,5-1 -1,5-2 0 5 10 15 20 25 Hangover Symptoms Scale

Winward et al., in press, JINS 19 Recovery with Abstinence p=.009

20 Summary Adolescent heavy drinkers show: 10% less information retrieved Reduce spatial skills for girls Can recover with abstinence Do problems relate to brain?

21 MRI Safe Non-invasive No radioactivity Issues Motion Artifact

Medina, Nagel et al., 2007, NTT 22 Hippocampal Volume Critical for memory Ages 15-18 3+ days abstinence Left hippocampus smaller in drinkers Right / Left

Medina, Tapert et al., 2008 23 Prefrontal Cortex Volume Key for planning and reasoning Ages 15-17 3+ days abstinence Smaller in drinkers Especially girls Anterior Ventral

Lisdahl et al., 2013, Psychiatry Research 24 Cerebellar Volume Important for balance and attention Higher peak drinks predicted smaller: Left cerebellar gray matter Left cerebellar white matter Right cerebellar gray matter Improves with abstinence

Volume Changes After Drinking Smaller volumes in future drinkers: Areas key to inhibition Reductions after drinking: Temporal gyrus Thalamus Caudate Brain stem Squeglia et al., in press, Developmental Cog Nsci 25

McQueeny, Schweinsburg, Jacobus, Bava, Frank, & Tapert, 2009, ACER 26 White Matter in Binge Drinkers Bingers poorer than Controls

Higher BAL Worse White Matter McQueeny, Schweinsburg, Jacobus, Bava, Frank, & Tapert, 2009, ACER 27

Mean Diffusivity <-- better -- worse --> Bava et al., 2013, ACER 28 Increased Drinking Worse White Matter Right Superior Longitudinal Fasciculus Integrity, Time 2 0,65 Users 0,6 showed poorer white matter integrity than Controls in 7 tracts (p<.01) 0,55 0,5 0 200 400 600 Drinking Days Between Scans

29 Functional MRI MRI Task Changes in blood oxygenation Identify areas involved in task

Brain Activation Brain Activation and Early Drinking Early drinking (1-2 yrs) Pre-initiation Substance Use Continued use Tapert et al., 2001, ACER; Tapert et al., 2004, ACER; Squeglia et al., 2012, JSAD 30

Squeglia, Pulido, Wetherill, Jacobus, Brown, & Tapert, 2012, JSAD 31 Activation Differences over Time N=40 age 14 20 binging by age 17 20 matched non-drinkers Before drinking: Future drinkers: activation After drinking: activation

Summary of Findings Alcohol Marijuana Cognition Brain volume White matter Activation Retrieval Spatial Attention Hippocampus Prefrontal Cerebellum Quality Spatial Learning Inhibition Jacobus & Tapert (2013). Annual Review of Clinical Psychology Learning Sequencing Errors = Quality Spatial Learning Inhibition 32

33 Adolescent Binge Drinking What is normal adolescence? How do binge drinkers differ? Does the media have a role? Prevention implications

34 Role of Media Food Violence Sex Tobacco Alcohol $3 billion/yr

Alcohol Ads & Underage Drinking Ad awareness More positive views on alcohol effects Greater plans to drink as adults Boys more aware than girls Ad liking More likely to drink Humor Story People with youth appeal Animals 35

Tapert et al., 2003, Arch Gen Psychiatry Alcohol Cue Task Alcohol Pictures Non-Alcohol Pictures + + + +

Youth Response to Alcohol Ads Alcohol pictures relative to non-alcohol pictures: LEFT HEMISPHERE Posterior Posterior cingulate cingulate Nucleus Accumbens Orbital/prefrontal Hypothalamus Temporal Prefrontal Heavy drinkers had more response to alcohol pictures than Light drinkers

Tapert et al., 2003, Arch Gen Psychiatry Signal Contrast Youth Response to Alcohol Ads 15 10 5 0-5 side view -10-15 Red: Heavy > Light Blue: Light > Heavy Light Drinker Heavy Drinker 0 20 40 60 80 100 120 Drinks per Month

Heavy Drinking Adolescents Neurocognition Females: visuospatial fxn, Males: attention Brain size reductions White matter worsens Actively developing Worst for heaviest drinkers Use Brain Brain activation Increases: brain has to work harder 39

40 Adolescent Binge Drinking What is normal adolescence? How do binge drinkers differ? Does the media have a role? Prevention implications

41 Prevention Implications 1. Inform students of risks Don t get hungover! >12 drinks/mo may harm females cognition 2. Heavy use linked to impaired learning Can improve after >2 weeks of no using Before then, have info repeated 3. Delay the start of using alcohol