The Teen Brain. What s Going on in There? Sion Kim Harris, PhD. Boston Children s Hospital Harvard Medical School

Transcription

1 The Teen Brain What s Going on in There? Sion Kim Harris, PhD Boston Children s Hospital Harvard Medical School

2 Center for Adolescent Substance Abuse Research

3 Leading Causes of Mortality, Ages 10-24, United States, 2010 Motor Vehicle Crashes 35% Other Unintentional Injuries (e.g., Poisoning) 14% Homicides 17% Suicides 11% TOTAL 72% Source: US DHHS, Health Resources and Services Administration, Maternal and Child Health Bureau. Child Health USA Rockville, Maryland: U.S. Department of Health and Human Services, 2010.

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7 The Age of the Brain Any Questions? 7

8 The human brain weighs about the same as a. A. Donut B. Six-pack of soda C. Chihuahua

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10 Until recently, brain development was thought to be complete by about age 12 Teen Brain Adult Brain 10

11 Brain Weight by Age Males Females Newborn Age Source: Dekaban, A.S. and Sadowsky, D. Annals of Neurology, 4: ,

12 What we now know Adolescence is a critical period in brain development. The brain is still developing until about age 24!!! Slide courtesy of Ken Winters, PhD. 12

13 What is a critical period in brain development? 13

14 Drs. David Hubel and Torsten Wiesel Source: Hubel, D. Eye, Brain, and Vision.

15 Fixing cataracts in children didn t restore sight Source: UCSF.edu

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19 Critical Period Definition: A window in brain development when a part of the brain develops rapidly highly sensitive to being shaped by experience and environmental exposures

20 Construction Ahead Around age 12, brain cells start to undergo pruning process guided by use it or lose it Slide courtesy of Ken Winters, PhD.

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23 Construction Ahead At the same time, myelin starts to cover neurons Helps neurons communicate 100 times faster Slide courtesy of Ken Winters, PhD. 23

24 The Brain s Information Superhighway: Myelinated axons = White Matter Tracts Source: Gordon J. Harris, PhD. 24

25 Construction Ahead Result when pruning and myelination are complete: faster, but fewer, connections in the brain critical period closes Slide courtesy of Ken Winters, PhD. 25

26 Pruning and myelination from age 5 to 20 Neuropsychopharmacology Reviews advance online publication 22 October doi: /npp

27 Copyright 2013 John R Knight MD, Center for Adolescent Substance Abuse Research (CeASAR), Boston Children s Hospital. All rights reserved. Brain Development is shaped by genes & experiences at critical points in time 27

28 Key Point: Teen brain highly neuroplastic Adolescence is an important window of opportunity and sensitivity for the brain How the brain is used during adolescence, and what it is exposed to, will have lifelong effects

29 This is Your (Developing) Brain on Drugs

30 Age at First Drink and Risk of Alcohol Addiction % with Alcohol Disorder Age at First Drink Source: Hingson RW, Heeren T, Winter MR. Age at drinking onset and alcohol dependence. Arch Pediatr Adolesc Med. 2006;160:

31 Age at First Use and Risk of Marijuana Addiction Source: Substance Abuse and Mental Health Services Administration. (2010). Results from the 2009 National Survey on Drug Use and Health: Volume I. Summary of National Findings (Office of Applied Studies, NSDUH Series H-38A, HHS Publication No. SMA Findings). Rockville, MD.

32 Why are adolescents more vulnerable to developing addiction?

33 Teen brains are affected by alcohol and drugs differently from adult brains Let s look at the evidence regarding alcohol Slide courtesy of Ken Winters, PhD. 33

34 Animal Studies Compared to adult rats, adolescent rats found to be less sensitive to alcohol with regards to its Sedative effects Motor impairment Slide courtesy of Ken Winters, PhD. Sources: White AM, Truesdale M, Bae J, et al. Differential effects of alcohol on motor coordination in adolescent and adult rats. Pharmacology Biochemistry and Behavior. 2002;73: Silveri MM, Spear LP. Decreased sensitivity to the hypnotic effects 34 of ethanol early in ontogeny. Alcoholism: Clinical and Experimental Research. 1998;22:

35 Amount of Alcohol Needed for Sedation by Rat s Age Alcohol-induced sedation Time to Turning Over by Age Slide courtesy of Marisa Silveri, PhD. Source: Silveri M & Spear L, Alcoholism: Clinical and Experimental Research. 1998;22:

36 Motor Performance: The Water Maze Test End 36

37 The Water Maze Test End 37

38 Results of Water Maze Test Swimming Speed (Motor strength and control) Finding Platform (Learning, problemsolving) Adult Adolescent Adult Adolescent Alcohol vs. Saline SAME White, A. M., Truesdale, M., Bae, J., Ahmad, S., Wilson, W. A., Best, P., et al. (2002). Differential effects of alcohol on motor coordination in adolescent and adult rats. Pharmacology Biochemistry and Behavior, 73,

39 Drunk Adult Drunk Adolescent Slide courtesy of John R Knight, MD.

40 Wide-Awake Drunk Teens Source: Boston Globe August 21, 2003 Slide courtesy of John R Knight, MD.

41 Teen brains react to rewarding things Brain areas with greatest changes during adolescence Front differently from adults Back Source: Sowell ER, Thompson PM, Holmes CJ, Jernigan TL, Toga AW. In vivo evidence for post-adolescent brain maturation in frontal and striatal regions. Nature Neuroscience. 1999;2: Used with permission.

42 The Reward Pathway Source: NIDA Ventral-Tegmental Area

43 Comparing Reward Pathway Function across Age Groups Study participants in MRI scanner asked to play a money game with small, medium, or large rewards Source: Galvan A et al. Journal of Neuroscience, 2006,26(25):

44 Studying the Living Brain: Functional Magnetic Resonance Imaging (fmri) Movies of brain activity Measures blood flow to brain areas that are active Slide courtesy of Susan Tapert, PhD. 44

45 BRAIN RESPONSE TO SMALL REWARD Children ages 7-11 Teens ages Adults ages Source: Galvan A, Hare AT, Parra, CE, Penn J, Voss H, Glover G, Casey BJ, Earlier Development of the Accumbens Relative to Orbitofrontal Cortex Might Underlie Risk-Taking Behavior in Adolescents. Journal of Neuroscience, 2006,26(25):

46 BRAIN RESPONSE TO LARGE REWARD Children ages 7-11 Teens ages Adults ages Source: Galvan A, Hare AT, Parra, CE, Penn J, Voss H, Glover G, Casey BJ, Earlier Development of the Accumbens Relative to Orbitofrontal Cortex Might Underlie Risk-Taking Behavior in Adolescents. Journal of Neuroscience, 2006,26(25):

47 Adolescent brains have a greater response to HIGHLY STIMULATING activities, like 47

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51 Source: NIDA marijuana

52 Some parts of the brain develop slower Brain areas with greatest changes during adolescence Front than others Back Source: Sowell ER, Thompson PM, Holmes CJ, Jernigan TL, Toga AW. In vivo evidence for post-adolescent brain maturation in frontal and striatal regions. Nature Neuroscience. 1999;2: Used with permission.

53 Pre-Frontal Cortex Functions Our internal CEO : critical for executive functions, such as Impulse control Decision-making Organizing and planning Abstract thought, rational thinking Attention, focus Working memory

54 Pruning and myelination from age 5 to 20 Neuropsychopharmacology Reviews advance online publication 22 October doi: /npp

55 Braking and Accelerating in the Adolescent Brain The gas pedal develops faster than the braking system Adult Source: Casey BJ, et al., Development Reviews. 2008; 28(1): Source: Casey BJ, Getz S, Galvan A. The adolescent brain. Dev Rev. 2008;28(1): Used with permission.

56 Brain Connectivity with Maturation Front Source: Dosenbach et al. Science. 2010;329:

57 The Developing Brain: Implications for Teens Less ability to inhibit impulses and strong emotions Higher physical tolerance and stronger reward response to addictive substances More vulnerable to developing a problem with alcohol and drugs Slide courtesy of Ken Winters, PhD. 57

58 International Comparison of Binge Drinking Rates*, 2014 (*6+ drinks in a row) Minimum legal drinking age: for beer

59 International Comparison of Binge Drinking Rates*, 2014 (*6+ drinks in a row)

60 Alcohol and Marijuana Effects on Teen Memory and Cognition 60

61 Hippocampus: The Key to the SAT s 61

62 The Human Hippocampus and Alcohol 10-35% smaller among heavydrinking teens hippocampus Slide courtesy of Susan Tapert, PhD. Nagel BJ, Schweinsburg AD, Phan V, Tapert SF. Reduced hippocampal volume among adolescents with alcohol use disorders without psychiatric comorbidity. Psychiatry Research Neuroimaging. 2005;139:

63 How does this affect brain function? Functional magnetic resonance imaging (fmri) Non-invasive Movies of brain activity Slide courtesy of Susan Tapert, PhD. 63

64 Teen Drinking & Brain Activity in Memory Task Non-Drinkers Heavy Drinkers Age 16 Activation Age 20 De-activation Slide courtesy of Susan Tapert, PhD. Tapert SF, Brown GG, Kindermann SS, Cheung EH, Frank LR, Brown SA. fmri measurement of brain dysfunction in alcohol-dependent young women. Alcoholism: Clinical and Experimental Research. 2001;25(2):

65 Marijuana effects on memory and cognitive function

66 THC and Memory THC suppresses activity of hippocampal neurons below the level needed to trigger memory formation With chronic THC exposure, neuron connections involved in memory are gradually lost due to continual suppression Source: Iversen L. How cannabis works in the brain. In Marijuana and Madness. Ed. Castle & Murray, Oxford University Press.

67 The Dunedin Study (New Zealand) (N=1,037) 13 yrs (Pre-initiation) 18 yrs 21 yrs 32 yrs 38 yrs Assessment ages Source: Meier et al. PNAS, 2012

68 Change in IQ from 13 to 38 yrs old 13 yrs old 38 yrs old Average IQ Never used marijuana

69 Change in IQ from 13 to 38 yrs old Average IQ Never used marijuana Used marijuana 3+ years

70 IQ Change by Age when Weekly Use Began, Among Those No Longer Using at age 38 Source: Meier et al. PNAS, 2012 Before Age weekly use began

71 STUDIES Cognitive Effects Brain Structure Brain Function Meier et al., 2012 Pope et al., 2003 Ehrenreich et al., 1999 IQ IQ attention Huestegge et al., 2002 Fontes et al., 2011 Solowij et al., 2012 visual search task executive functioning executive functioning Churchwell et al., 2010 prefrontal cortex volume Gruber et al., 2011 impulsivity white matter integrity in prefrontal cortex Lopez-Larson et al., 2011 Wilson et al., 2000 Becker et al., 2010a Gruber et al., 2012 Jager et al., 2010 prefrontal cortex thickness total gray matter, prefrontal cortex activity during working memory task anterior cingulate activity during inhibition task prefrontal cortex activity during in working memory

72 Marijuana and Mental Illness

73 Marijuana and Mental Disorders Times Used Illness Increase in Risk 1 Schizophrenia 1.2X 50 + Schizophrenia 6.7X Weekly Daily Depression & Anxiety Depression & Anxiety 2X 5X Lynskey et al., Arch Gen Psychiatry, 2004;61(10): Patton et al., British Medical Journal, 2002;325: Zammit S et al., BMJ, 2002;325:1199. Degenhardt et al., Addiction. 2012:108:

74 Genetic Risk 7 times higher risk for psychosis with C/C variant Source: Di Forti et al. Biol Psychiatry

75 Avg. % THC Content among Confiscated Cannabis Products in U.S. ( ) ~12% ~4% *Source: ElSohly et al., Biological Psychiatry, *38,681 samples

76 As THC content increases, we see more adverse effects: Paranoia Anxiety and panic Hallucinations Erratic mood swings Aggressive behavior Source: National Drug Abuse Warning Network, 2011

77 Teen Brain Plasticity It s a double-edged sword Vulnerability Opportunity

78 QuickTime and a decompressor are needed to see this picture.

79 Advise DELAYING use until age 21+

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