Ken Winters, Ph.D. Department of Psychiatry University of Minnesota winte001@umn May 10, 2011

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

2. Adolescence is a Time-Limited Brain Disorder!

3. Acknowledgements 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)

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

5. Addiction as brain • disease • Clinical • opportunities • Brain • development • Summary • Alcohol • susceptibility

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. Addiction as brain • disease

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

11. Your Brain on Cocaine PET scan 1-2 Min 3-4 5-6 6-7 7-8 8-9 9-10 10-20 20-30 Yellow = cocaine is binding or attaching itself to areas of the brain

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

13. What about recovery?

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

15. ADDICTION CAN BE TREATED Partial Recovery of Brain Dopamine Transporters in Methamphetamine (METH) Abuser After Protracted Abstinence 3 0 ml/gm METH Abuser (1 month detox) Normal Control METH Abuser (24 months detox) Source: Volkow, ND et al., Journal of Neuroscience 21, 9414-9418, 2001.

16. Addiction as brain • disease • 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 thoughtbrain 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 Volume Adolescence Metabolism Blood Flow Receptors RATE OF CHANGE 7 1 2 16 30 Post-birth Age Prenatal Tapert & Schweinsburg (2005)

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

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

26. Construction Ahead • 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.

27. Maturation Occurs from Back to Front of the Brain Images of Brain Development in Healthy Youth (Ages 5 – 20) Earlier development: Motor Coordination Emotion Motivation Later development: Judgment Process: Promotes puberty Blue represents maturing of brain areas Source: PHAS USA 2004 May 25; 101(21): 8174-8179. Epub 2004 May 17.

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

29. Implications of Brain Development for Adolescent Behavior • Preference for… • physical activity • high excitement and rewarding activities • activities with peers that trigger high intensity/arousal • novelty • Less than optimal… • control of emotional arousal • consideration of negative conseq. • Greater tendency to… • be attentive to social information • take risks and show impulsiveness

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) Outcomes were converted to Z-Scores and childhood self-control is represented in quintiles.

32. Implications of Brain Development for Adolescent Behavior • Preference for …. • physical activity • high excitement and rewarding activities • activities with peers that trigger high intensity/arousal • novelty • Less than optimal.. • control of emotional arousal • consideration of negative conseq. • Greater tendency to… • be attentive to social information • take risks and show impulsiveness

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. Addiction as brain • disease • Brain • development • 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 ratstudies.

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) Fewer Problems in Those Who Start Later % Age Started Drinking

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 • Saline vs alcohol • Measures • Swimming speed • Time to find platform Slide courtesy Sion Kim Harris, Ph.D.

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.