1. Ken Winters, Ph.D. Department of Psychiatry University of Minnesota winte001@umn.edu May 10, 2011 Gainesville, FL Adolescence, the Maturing Brain and Alcohol: Intersections on the Developmental Highway

2. Adolescence is a Time-Limited Brain Disorder!

3. 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

4. Center for Adolescent Substance Abuse Research, University of Minnesota

5. 1. Addiction as brain disease 2.Brain development 3.Alcohol susceptibility 4.Summary 5.Clinical opportunities

6. 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).

7. Talks that are too technical can turn audiences into…

8. 1. Addiction as brain disease

10. Dopamine Neurotransmission VTA/SN nucleus accumbens nucleus accumbens frontal cortex frontal cortex 0 0 100 200 300 400 500 600 700 800 900 1000 1100 0 0 1 1 2 2 3 3 4 4 5 hr Time After Amphetamine % of Basal Release AMPHETAMINE 0 0 50 100 150 200 0 0 60 120 180 Time (min) % of Basal Release Empty Box Feeding Di Chiara et al. FOOD

11. Your Brain on Cocaine PET scan 1-2 Min3-45-6 6-77-88-9 9-1010-2020-30 Yellow = cocaine is binding or attaching itself to areas of the brain

12. DA D2 Receptor Availability Cocaine Alcohol DA Reward Circuits DA Reward Circuits DA Drug Abuser Non-Drug Abuser Heroin Meth Dopamine D2 Receptors are Lower in Addiction controladdicted

13. What about recovery?

14. Your Brain After Cocaine Normal Cocaine Addict - 10 days Cocaine Addict - 100 days Yellow = normal brain functioning

15. Partial Recovery of Brain Dopamine Transporters in 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

16. 1.Addiction as brain disease 2.Brain development

18. Cautions Brain imaging studies are based on small samples gender, ethnic and cultural differences may be significant.

19.  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!

20. 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 available until the age of 25?

21. Allstate ad, NY Times, May, 2007

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

23. Brain Development 12 7 16 30 Prenatal Post-birth Age RATE OF CHANGE  Volume Metabolism Blood Flow Receptors Tapert & Schweinsburg (2005) Adolescence

24. Brain Weight by Age Source: Dekaban, A.S. and Sadowsky, D. Annals of Neurology, 4:345-356, 1978 Newborn FemalesMales I’m adult-size now! Age Slide courtesy Sion Kim Harris, Ph.D.

25. Brain Development 12 7 16 30 Prenatal Post-birth Age RATE OF CHANGE  Myelination Synaptic Refinement Volume Metabolism Blood Flow Receptors Tapert & Schweinsburg (2005) Adolescence

26. 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

27. Maturation Occurs from Back to Front of the Brain Images 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

28. Impact of Peer Presence on Risky Driving in Simulated Context Chein et al., in press peer effect

29. 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

30. 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

31. Childhood Self-control as a Predictor of Adult Substance Use Dependence (Moffitt et al., in press) O utcomes were converted to Z-Scores and childhood self-control is represented in quintiles.

32. 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

33. An Immature Brain = Low Brain Power Source: US News & World Report, 2005

34. 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.

35. An Immature Brain = Absence of Judgment Source: US News & World Report, 2005

36. Taking risks is not always unhealthy. Growth experiences and extending one’s talents may involve risk-taking.

38. 1. Addiction as brain disease 2.Brain development 3.Drug susceptibility

39. 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.

40. 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.

41. Evidence from epidemiological studies Alcohol use starts early and peaks in the teen years

42. 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) %

43. Percentages of Past Year Alcohol Use Disorder (Abuse or Dependence) Among Adults Aged 21 or Older, by Age of First Use (SAMHSA, 2005) Age Started Drinking % Fewer Problems in Those Who Start Later

44. Are adolescents more susceptible to alcohol than adults? Comparing adolescent and adult rats, both having 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”

45. The Water Maze Test Hidden Slide courtesy Sion Kim Harris, Ph.D. Saline vs alcohol Measures -Swimming speed -Time to find platform

46. Are adolescents more susceptible to alcohol than adults? Adolescent rats are more sensitive to the social disinhibition effects of alcohol. greater social comfort from intoxication

47. Wanna look for some cheese with me? Sure!

48. Are adolescents more susceptible to alcohol than adults? 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.

49. Binge Alcohol Use in the Past Month by Age Group (SAMHSA, 2005) percent binge use past month Binge = 5+ drinks same occasion on at least one day in the past 30 days.

50. Are adolescents more susceptible to alcohol than adults? Alcohol may produce greater cognitive disruptions in adolescents.

51. Human Data: Alcohol’s Effects on Memory Adolescent rats more sensitive to… disruption in memory impairment of neurotransmission in hippocampus and cortex Where is my cheese? Source: Spear, 2002

52. Human Data: Alcohol’s Effects Verbal information Nonverbal information Retention Rate % Source: Brown et al., 2000

53. Human Data: Alcohol’s Effects on the Hippocampus Adolescents with a history of alcohol use disorder… Hippocampus volume (10%) Source: Tapert & Schweinsburg, 2005 Where is my iPod? Hippocampus converts information to memory

54. 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

55. Teen Drinking & Brain Activation Non-DrinkersHeavy Drinkers Activation De-activation Age 16 Age 20 Tapert et al., 2001, 2004 Slide courtesy of Susan Tapert, PhD. 2 yrs drinking 5 yrs drinking

56. What’s Affected by Marijuana?

57. Adverse Effects Decreased coordination and reaction time Impaired ability to concentrate Impaired memory and learning ability

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

59. 1. Addiction as brain disease 2.Brain development 3.Alcohol susceptibility 4.Summary

60. 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

61. 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.

62. Summary reward incentives > perception of consequences

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

64. 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

65. “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.

66. “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

67. DA D2 Receptor Availability Cocaine Alcohol DA Reward Circuits DA Reward Circuits DA Drug Abuser Non-Drug Abuser Heroin Meth Dopamine D2 Receptors are Lower in Addiction control addicted

68. “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?

69. Average Number of Self-Administered Doses of Nicotine When Rats Were Adults (Levin et al., 2003) Age of Rates When First Exposed to Nicotine. All Data Collected When Rats were Adults.

70. 1. Addiction as brain disease 2.Brain development 3.Alcohol susceptibility 4.Summary 5.Clinical opportunities

71. 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

72. Brain Development: Opportunities for Treatment 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.

73. Your Brain After Cocaine Normal Cocaine Addict - 10 days after use Cocaine Addict - 100 days after use Yellow = normal brain functioning

74. Brain Development: Opportunities for Treatment Discuss with teenagers the science of the neurobiology of addiction

75. DA D2 Receptor Availability Cocaine Alcohol DA Reward Circuits DA Reward Circuits DA Drug Abuser Non-Drug Abuser Heroin Meth Dopamine D2 Receptors are Lower in Addiction control addicted

76. Brain Development: Opportunities for Treatment Discuss the implications of using substances when the brain is still developing.

77. Memory Effects Verbal information Nonverbal information Retention Rate % Source: Brown et al., 2000

78. Brain Development: Opportunities for Treatment Shape milieu to be teen-brain friendly: structure and rules recreation sensory activities and active learning peer community novelty

79. Brain Development: Opportunities for Treatment Teach important skills not optimal for the teen brain impulse control “second” thought processes social decision making dealing with risk situations

80. 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

81. 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

82. Taking risks is not always unhealthy. Growth experiences and extending one’s talents may involve risk-taking.

83. Teen-brain friendly features of the 12-Step Model abstinence novelty – new approach to life structure spiritual component fellowship Brain Development: Opportunities for Treatment

84. Two major treatment approaches seem accommodating to the teen brain: Cognitive – behavioral therapy (CBT) Motivational interviewing Brain Development: Opportunities for Treatment

85. Characteristics of CBT Focus on immediate, relevant and specific problems Solutions are realistic, concrete, specific

86. 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

87. 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

88. 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

89. 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: winte001@umn.edu 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

90. Hazelden’s Brain Development Curriculum for High School Science Classes (eight 10-minute lessons)

91. School and community-based prevention programs

92. 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

93. Selected Examples of Prevention Programs Meeting 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.

94. 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.

95. 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.

96. Opportunities for Parents

97. 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.

98. Recipe for a Healthy Brain Good diet Vitamins (multi-vitamins) Exercise Sufficient sleep Social connections Learning music Positive thinking Helping others New learning

99. 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.

100. 1.Examine (and adjust if necessary) your own behavior and attitude concerning drugs 2.Have family talks about the issues of drug use 3.Have clear rules about what is expected in your teenager 4.Monitor your child’s adherence to the rules; apply rewards and consequences 5.Provide opportunities for healthy and positive activities Action Steps to Improve Likelihood of Raising a Drug Free Child

101. 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….

102. Parent programs Our research group has developed a parent presentation; e-mail me: winte001@umn.edu Mentor Foundation’s Prevention Smart Parents www.mentorfoundation.org New web-based resources from Partnership for a Drug-Free America www.drugfree.org/Parent/

105. THANK YOU! winte001@umn.edu

106. 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.

107. 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

108. Contact Ken Winters, Ph.D. winte001@umn.edu Comments or Questions?