This is Your Brain after the Drugs: Neural Functioning in Adolescent Substance Users. Susan F. Tapert, Ph.D. University of California, San Diego
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1 This is Your Brain after the Drugs: Neural Functioning in Adolescent Substance Users Susan F. Tapert, Ph.D. University of California, San Diego
2 Overview What is normal adolescence? Does substance use affect this? Does the media have a role? Implications 2
3 Past Month Use Monitoring the Future,
4 Teen Drinking Rates 28% 5% 72% 26% 55% Alcohol use disorder (AUD) Binge, past 2 weeks Ever got drunk Any alcohol use ever No drinking by 12 th grade Monitoring the Future, 2009; National Household Drug Use & Health,
5 Gender Trends % who used any alcohol in past month % Boys 20 Girls th Grade 10th Grade 12th Grade Monitoring the Future,
6 Prevalence of Disorders 20% 15% % 5% 0% Alcohol Drugs National Household Drug Use & Health,
7 Age of First Drink National Household Drug Use & Health,
8 Quick Brain Review! 8
9 Gray & White Matter 9
10 Adolescent Brain Development Volume Metabolism Myelination Blood Flow Receptors Synaptic Refinement Adolescence RATE OF CHANGE Prenatal Post-birth - Age Tapert & Schweinsburg,
11 Gray Matter Development Gogtay et al.,
12 Volume (cm 3 ) Frontal Gray Matter Boys peak Girls peak Giedd et al., 1999, 2006 Age 12
13 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 N=22 Bava, Thayer, Jacobus, Ward, Jernigan, & Tapert, 2010, Brain Research 13
14 Adolescent Substance Use What is normal adolescence? How do substance users differ? Does the media have a role? Implications 14
15 Participants Light Drinkers Heavy Drinkers MJ+Alc Users Age (15-19) Female 35% 37% 29% No FH of alcoholism 46% 42% 45% IQ Cigarettes/day <1 2 2 Drinks/month 4 42* 44* Lifetime MJ use * *p<.05 15
16 Study Design 16
17 Staying Abstinent 2-3x/week urine samples 70% stay abstinent 1 month Hardest for daily users 17
18 Memory The difference between an A and a B: Retention Rate 100% 95% 90% 85% 80% 75% Verbal Info Nonverbal Info Light Drinkers (n=24) Heavy Drinkers (n=33) Brown, Tapert, Granholm, & Delis, 2000, ACER 18
19 60 Attention Light Drinkers (n=50) T-score Heavy Drinkers (n=101) 45 Attention Speeded Info Processing Tapert & Brown, 2000, Addictions 19
20 Marijuana Users Medina, Hanson, Schweinsburg, Cohen-Zion, Nagel, & Tapert,
21 Summary Adolescent heavy drinkers show: 10% less information retrieved Attention / processing speed +Marijuana: poor learning more errors Do problems relate to brain? 21
22 MRI Safe Non-invasive No radioactivity Issues Motion Artifact 22
23 Hippocampus Left Hippocampus % Smaller in heavy drinking youth Right / Left Light Drinkers (n=16) Heavy Drinkers (n=21) Medina, Schweinsburg, Cohen-Zion, Nagel, & Tapert, 2007, NTT 23
24 Frontal Lobes Ventral Prefrontal Volume%.060 Prefrontal cortex: Light Drinkers (n=17) Heavy Drinkers (n=14) Ventral Medina, McQueeny, Nagel, Hanson, Schweinsburg, & Tapert, 2008, ACER 24
25 Gender Effects Ventral Prefrontal / ICV (cc3) Light Drinkers Heavy Drinkers Boys Girls Medina, McQueeny, Nagel, Hanson, Schweinsburg, & Tapert, 2008, ACER 25
26 Gender Effects 0.25 Prefrontal Cortex Size/ICV (cc3) Controls MJ Users Boys Girls Medina, McQueeny, Nagel, Hanson, Yang, & Tapert, 2009, Addiction Biology 26
27 White Matter in Binge Drinkers Bingers (n=14) poorer than Controls (n=14) R Corrected p<.01 L McQueeny, Schweinsburg, Jacobus, Bava, Frank, & Tapert, 2009, ACER. 27
28 High BAC Worse White Matter 0.8 Frontal White Matter <- worse -- better -> r = Binge Drinkers (n=14) Non-Drinkers (n=14) Peak BAL in past 3 months L McQueeny, Schweinsburg, Jacobus, Bava, Frank, & Tapert, 2009, ACER. 28
29 Functional MRI MRI Task Changes in blood oxygenation Identify areas involved in task 29
30 Spatial Working Memory Task SPATIAL WORKING MEMORY TARGET TRIAL + + SIMPLE ATTENTION + TARGET TRIAL + + TARGET TRIAL + + Tapert et al., 2001,
31 DOTS 31
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42 1-2 Years of Heavy Drinking Spatial Memory Task 19 Non-Drinkers 88% accurate 15 Heavy Drinkers 90% accurate t = +4.4 Parietal Heavy>Non Occipital Heavy<Non Cerebellum Heavy<Non t = -4.2 Tapert et al., 2004, ACER 42
43 4-5 Years of Heavy Drinking Task: SWM 10 Non-Drinkers 91% accurate 10 Heavy Drinkers 82% accurate R t = +4.4 Frontal Heavy<Non Parietal Heavy<Non t = -4.2 Tapert et al., 2001, ACER 43
44 Gender Differences Female binge drinkers: Heaviest drinkers less activation Less activation worse performance Male binge drinkers: Heaviest drinkers more activation More activation better performance Squeglia et al., submitted. 44
45 Adolescent Marijuana Use 15 MJ users and 17 non-users, No task performance differences Parietal MJ>Control Occipital MJ<Control Frontal MJ<Control Schweinsburg, Nagel, Park, Theilmann, & Tapert., 2008, Psychiatry Research 45
46 Verbal Encoding 1. Before scan: memorize 16 word pairs 2. During scan: view old and new word pairs 3. After scan: test recall of pairs MERMAID TAIL TOAST BREAD SINK DRAIN 46
47 Verbal Memory in Bingers Drinkers showed: 1. Poorer recall Parietal Right frontal 2. occipital response 3. frontal & parietal response 4. No differential activation to novelty Occipita l Schweinsburg, McQueeny, Nagel, Eyler, & Tapert, 2010, Alcohol. 47
48 Verbal Encoding: Marijuana No task performance differences MJ users show LESS occipital and MORE frontal activation No activation of hippocampus Schweinsburg, Nagel, Eyler, & Tapert, in press, Addictions. 48
49 Inhibition Task Instructions: Press the button as soon as you see a blue shape EXCEPT the SMALL blue square Respond as FAST as you can! GO GO GO NO-GO! TARGET TRIAL GO Schweinsburg et al., 2004; Anderson et al., 2005; Tapert et al.,
50 Inhibition: MJ MJ using teens (n=16) had more inhibition response than controls (n=17) Parietal Frontal Tapert et al., 2007, Psychopharmacology 50
51 Nicotine Performance: cognitive flexibility Further by alcohol withdrawal Brain response: brain response to pattern recognition task Greatest effect for early onset smoking 51
52 Initiation of Drinking: Girls More drinks worse picture memory p<.05 Squeglia, Spadoni, Infante, Myers, & Tapert, 2009, Psychology Addictive Behaviors 52
53 Initiation of Drinking: Boys More hangovers worse attention p<.05 Squeglia, Spadoni, Infante, Myers, & Tapert, 2009, Psychology Addictive Behaviors 53
54 Continued Drinking Block Design Scaled Score Light Drinkers (n=26) Heavy Drinkers (n=47) 10 Age 16 Age 24 Tapert et al., 2002, JINS 54
55 Recovery with Abstinence 19 users 21 non-users Verbal Memory Working Memory Attention Hanson, Winward, Schweinsburg, Medina, Brown, & Tapert, 2010, Addictive Behaviors. 55
56 Summary of Findings Cognition Brain volume White matter integrity Activation Alcohol Retrieval Spatial Hippocampus Prefrontal Quality Spatial Learning = Inhibition Marijuana Learning Sequencing Errors = Quality Spatial Learning Inhibition 56
57 Adolescent Substance Use What is normal adolescence? How do substance users differ? Does the media have a role? Implications 57
58 Role of Media Food Violence Sex Tobacco Alcohol $2 billion/yr 58
59 Alcohol Ads & Youth 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 59
60 Alcohol Cue Task Alcohol Pictures Non-Alcohol Pictures Tapert et al., 2003, Arch Gen Psychiatry 60
61 Youth Response to Alcohol Ads Alcohol pictures relative to non-alcohol pictures: LEFT HEMISPHERE Orbital/prefrontal Heavy drinkers (n=15) had more response to alcohol pictures than Light drinkers (n=15) 61
62 Youth Response to Alcohol Ads Alcohol pictures relative to non-alcohol pictures: LEFT HEMISPHERE Prefrontal Heavy drinkers (n=15) had more response to alcohol pictures than Light drinkers (n=15) 62
63 Youth Response to Alcohol Ads Alcohol pictures relative to non-alcohol pictures: LEFT HEMISPHERE Nucleus Accumbens Heavy drinkers (n=15) had more response to alcohol pictures than Light drinkers (n=15) 63
64 Youth Response to Alcohol Ads Alcohol pictures relative to non-alcohol pictures: LEFT HEMISPHERE Nucleus Accumbens Heavy drinkers (n=15) had more response to alcohol pictures than Light drinkers (n=15) 64
65 Youth Response to Alcohol Ads Alcohol pictures relative to non-alcohol pictures: LEFT HEMISPHERE Nucleus Accumbens Heavy drinkers (n=15) had more response to alcohol pictures than Light drinkers (n=15) 65
66 Youth Response to Alcohol Ads Alcohol pictures relative to non-alcohol pictures: LEFT HEMISPHERE Nucleus Accumbens Heavy drinkers (n=15) had more response to alcohol pictures than Light drinkers (n=15) 66
67 Youth Response to Alcohol Ads Alcohol pictures relative to non-alcohol pictures: LEFT HEMISPHERE Hypothalamus Heavy drinkers (n=15) had more response to alcohol pictures than Light drinkers (n=15) 67
68 Youth Response to Alcohol Ads Alcohol pictures relative to non-alcohol pictures: LEFT HEMISPHERE Hypothalamus Heavy drinkers (n=15) had more response to alcohol pictures than Light drinkers (n=15) 68
69 Youth Response to Alcohol Ads Alcohol pictures relative to non-alcohol pictures: LEFT HEMISPHERE Posterior cingulate Heavy drinkers (n=15) had more response to alcohol pictures than Light drinkers (n=15) 69
70 Youth Response to Alcohol Ads Alcohol pictures relative to non-alcohol pictures: LEFT HEMISPHERE Posterior cingulate Heavy drinkers (n=15) had more response to alcohol pictures than Light drinkers (n=15) 70
71 Youth Response to Alcohol Ads Alcohol pictures relative to non-alcohol pictures: LEFT HEMISPHERE Heavy drinkers (n=15) had more response to alcohol pictures than Light drinkers (n=15) 71
72 Youth Response to Alcohol Ads Alcohol pictures relative to non-alcohol pictures: LEFT HEMISPHERE Heavy drinkers (n=15) had more response to alcohol pictures than Light drinkers (n=15) 72
73 Youth Response to Alcohol Ads Alcohol pictures relative to non-alcohol pictures: LEFT HEMISPHERE Heavy drinkers (n=15) had more response to alcohol pictures than Light drinkers (n=15) 73
74 Youth Response to Alcohol Ads Alcohol pictures relative to non-alcohol pictures: LEFT HEMISPHERE Heavy drinkers (n=15) had more response to alcohol pictures than Light drinkers (n=15) 74
75 Youth Response to Alcohol Ads Alcohol pictures relative to non-alcohol pictures: LEFT HEMISPHERE Heavy drinkers (n=15) had more response to alcohol pictures than Light drinkers (n=15) 75
76 Youth Response to Alcohol Ads Alcohol pictures relative to non-alcohol pictures: LEFT HEMISPHERE Heavy drinkers (n=15) had more response to alcohol pictures than Light drinkers (n=15) 76
77 Youth Response to Alcohol Ads Alcohol pictures relative to non-alcohol pictures: LEFT HEMISPHERE Heavy drinkers (n=15) had more response to alcohol pictures than Light drinkers (n=15) 77
78 Youth Response to Alcohol Ads Alcohol pictures relative to non-alcohol pictures: LEFT HEMISPHERE Heavy drinkers (n=15) had more response to alcohol pictures than Light drinkers (n=15) 78
79 Youth Response to Alcohol Ads Alcohol pictures relative to non-alcohol pictures: LEFT HEMISPHERE Temporal Heavy drinkers (n=15) had more response to alcohol pictures than Light drinkers (n=15) 79
80 51 0 Youth Response to Alcohol Ads side view Signal Contrast Red: Heavy > Light -15 Blue: Light > Heavy Light Drinker Drinks per Month Tapert et al., 2003, Arch Gen Psychiatry 80
81 Adolescent Substance Use What is normal adolescence? How do substance users differ? Does the media have a role? Implications 81
82 Summary: Teen Substance Users Abnormalities in brain functioning Poorer neurocognition Abnormal brain part sizes Poorer white matter Abnormal activation Enhanced cue response Worse for girls? 82
83 Prevention Implications Start early: more problems Cognitive Psychiatric Inform teens of risks Difference between A and B 83
84 What Can Be Done? Counter ads: 84
85 Treatment Implications Repeat information Encourage brain power Ask teens opinions Goals, activities, hope 85
86 Promoting Long-Term Success Reduce environmental risks Remove substances from home Watch out for group therapies Increase resources Alternative activities Sports, music Volunteer Pets Non-using peers Motivate 86
87 Feedback Brain of 16-year old non-drinking girl Your brain 87
88 Conclusions 1. Adolescent brains are developing 2. Substance users show abnormalities Even if don t meet for AUD 3. Girls even more at risk Hangover/withdrawal 4. Adolescent drinkers brains respond to ads 88
89 Acknowledgments: National Institute on Drug Abuse, National Institute on Alcohol Abuse and Alcoholism Back: Lindsay Squeglia MS, Sonia Lentz, Megan Ward, Omar Mahmood PhD, Joanna Jacobus MS, MJ Meloy PhD, Lorenzo Campanelli, Norma Castro, Anthony Scarlett, Veronique Boucquey, Alejandra Infante. Front: Carmen Pulido PhD, Karen Hanson PhD, Sunita Bava PhD. Also: Sandy Brown PhD, Sonja Eberson MS, Krista Medina PhD, Bonnie Nagel PhD, Alecia Schweinsburg PhD, Marc Schuckit MD, Andrea Spadoni PhD. P 89
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