Prevention of Substance Abuse in Adolescents: Lessons from the Brain Sciences - PowerPoint PPT Presentation

1 / 78
About This Presentation
Title:

Prevention of Substance Abuse in Adolescents: Lessons from the Brain Sciences

Description:

Kaplan-Meier Survival Curves for Remaining Non Alcohol Dependent ... Brain development is different between women and men and even different between identical twins. ... – PowerPoint PPT presentation

Number of Views:112
Avg rating:3.0/5.0
Slides: 79
Provided by: jef72
Category:

less

Transcript and Presenter's Notes

Title: Prevention of Substance Abuse in Adolescents: Lessons from the Brain Sciences


1
Prevention of Substance Abuse in Adolescents
Lessons from the Brain Sciences
  • Jeffery N. Wilkins, M.D.
  • Lincy / Heyward-Moynihan, Chair
  • in Addiction Medicine
  • Vice Chair, Dept. of Psychiatry
  • Cedars-Sinai Med Center
  • Professor, Dept. of Psychiatry
  • David Geffen School of Medicine _at_ UCLA

2
Conflict of Interest Disclosure
  • Jeffery N. Wilkins, M.D.
  • Consultant Alkermes Inc., Cephalon, Inc.,
    Hythiam, Inc.
  • Unrestricted Research Grant Hythiam, Inc.
  • Honoraria CME LLC
  • Member, Board of Directors
  • Brent Shapiro Foundation for Drug Awareness
  • California Society of Addiction Medicine
  • Psychological Trauma Center

3
Goals of Presentation
  • Describe 3 major public health problems with
    substance use in children and adolescents
  • Describe brain mechanisms that may contribute to
    these 3 major public health substance use
    problems
  • Discuss overall risk model for prevention of
    alcohol, drugs and cigarette use in children and
    adolescents with specific focus on brain
    development and genetics

4
Learning Objectives
  • 1. At the completion of this presentation, the
    attendee will be able to describe key age windows
    of risk for substance use by children and
    adolescents and their relationship to stages of
    brain development.
  • 2. At the completion of this presentation, the
    attendee will be able to describe where addiction
    is manifested in select areas of the brain
    including the prefrontal cortex.

5
Learning Objectives
  • 3. At the completion of this presentation, the
    attendee will be able to describe strategies for
    prevention of substance abuse in children and
    adolescents based on lessions from the brain
    sciences.

6
Three Major Public Health Problems
  • Development of Dependence (i.e., Addiction)
    occurs from changes in the brain that occur
    following chronic and regular use of most
    substances of abuse. Although amenable to
    treatment intervention, these changes in the
    brain are semi-permanent or permanent
  • Substance use in children lt 14 leads to high
    rates of substance problems in adulthood
  • Nicotine and probably other select substances of
    abuse induce significant semi-permanent to
    permanent changes in the brain with even casual
    use

7
Public Health Problem 1 Chronic and Regular
Substance Use Leads to Alteration of
Neurobiological Mechanisms that Regulate
Motivated Behavior
8
Substances Alter Neurobiological Mechanisms of
Motivated Behavior
  • Select brain areas assign a degree of importance
    to our behaviors, thereby shaping our behavior.
  • When addiction is not present, these behaviors
    target the obtaining of desired items/life events
    and avoidance of undesired items/life events .
  • When addiction is present, changes to key brain
    areas (e.g. prefrontal cortex, nucleus accumbens,
    amygdala) are altered and motivated behavior is
    diverted to drug use cues and away from normal
    life processes. This has been demonstrated in
    animal and human studies of cocaine dependence
    and normal controls.
  • Kalivas and Volkow. The neural basis of
    addiction a pathology of motivation and choice
    (2005), Am J Psych 1621403-1413

9
(No Transcript)
10
Cellular Site of Action for Naltrexone
11
Circuitry Mediating Activation of Goal-Directed
Behavior
Kalivas Volkow, 2005
12
GABA and Glutamate Role in Motivation
Dopamine
GABA
Glutamate
Adapted from Kalivas and Nakamura, Curr. Opin.
Neurobiol., 1999.
13
Neural Circuitry Mediating Drug Seeking
Kalivas Volkow, 2005
14
Addiction and the Brain as Shown by MRI
15
Salience List Model Pre-Exposure
  • FOOD
  • FAMILY
  • AVOID DANGER

16
Salience Model Post-Exposure
  • FOOD
  • FAMILY
  • AVOID DANGER
  • DRUG CUES
  • (Fueled by Stress)

17
Salience Model Dependence
  • FOOD
  • FAMILY
  • AVOID DANGER
  • DRUG CUES
  • (Fueled by Stress)

18
Salience Model Treatment
  • FOOD
  • FAMILY
  • AVOID DANGER
  • DRUG CUES
  • (Fueled by Stress)

Reinstate Natural Reinforcers
Mitigate Cue Stimulation and Diminish Stress
19
Public Health Problem 2 Substance use in
children lt 14 leads to high rates of substance
problems in adulthood
20
Flexibility Invites Vulnerability
  • Our brains are sculpted by our early
    experiences. Maltreatment is a chisel that shapes
    a brain to contend with strife, but at the cost
    ofdeep, enduring wounds.
  • Teicher, 2000
  • Plasticity is a double-edged sword that leads to
    both adaptation and vulnerability.
  • Shonkoff Phillips, 2000

21
Stress, Early Drinking, Alc. Dependence
  • Nationwide survey of 27,000, mean age 43
  • Persons who started alcohol use lt14 and reported
    gt6 stressors in past year drank average of 6
    drinks per day 5x that of similarly stressed
    individuals who started drinking at age 18 or
    older.
  • Dawson et al., Alc Clin Exp Res, 2007

22
Defining the ProblemNational Surveys
  • Monitoring the Future (N50, 000)
  • National Survey on Drug Use Health (N68,000)
  • Ellickson et al., 2006 (N6,338)
  • Dawson et al., Alc Clin Exp Res, 2007 (N27,000)
  • Hingson et al., Arch Ped Adol Med, 2006 (N43,
    093)
  • Clark et al., 1998 (N262)

23
Monitoring the Future (www.monitoringthefuture.org
)
  • Approximately 50,000 8th, 10th and 12th grade
    students are surveyed (12th graders since 1975,
    and 8th and 10th graders since 1991).
  • Annual follow-up questionnaires are mailed to a
    sample of each graduating class for a number of
    years after their initial participation.
  • Funded by NIDA, conducted at U. of Michigan.

24
Age12 13Last 30days
25
NSDUH (50 states, N68, 000)
  • 74 of adults report beginning drinking prior to
    reaching the legal drinking age
  • 5.9 of children ages 12 to 17 meet criteria for
    alcohol dependence or abuse
  • Those reporting alcohol use lt 14 are 5 times more
    likely to report alcohol dependence after age 21
    (3 v. 16)
  • Only 5 percent (fewer than1 million persons) of
    adults classified as having past year alcohol
    dependence or abuse had started using alcohol at
    or after age 21
  • NSDUH Report 10/2004

26
Evaluation at Grade 7, 12 and age 23
  • Early drinkers enrolled in middle school and high
    school are more likely to report
  • academic problems
  • substance use
  • delinquent behavior
  • By the time early drinkers reach the age of 23
    they are more likely to have
  • Employment problems
  • Other substance use problems
  • Legal problems
  • Problems with violence (Ellickson et
    al., 2006)

27
Grade 7 (Age 12 13)
Ellickson et al., 2006
28
FromAge 12to Age 17
Ellickson et al., 2006
29
FromAge 12 to Age 23
Ellickson et al., 2006
30
Survey of 43,093 Adults for Persons with 6 or 7
DSM IV Alcohol Dependence Criteria
  • Hingson et al., Arch Ped Adol Med 160739-746,
    2006

31
Background
  • Centers for Disease Control and Preventions 2003
    Youth Risk Behavior Survey of HS students
  • 28 drank alcohol other than a few sips before
    age 13 years
  • By age 17 years they were 7 times more likely to
    consume 5 or more drinks 6 or more times per
    month than those who waited until they were 17
    years or older to begin drinking.

Grunbaum J, Kaun L, Kinchen S, et al. Youth Risk
Behavior SurveillanceU.S., 2003. MMWR Surveill
Summ. 2004531-96
32
Start Alcohol lt14 vs gt 21
  • lt14
  • ? risk for alcohol dependence
  • ? likelihood within 10 years of 1st drink (CIs,
    1.78 1.51-2.11 and 1.69 1.38-2.07,
    respectively)
  • Odds of 2.62 (95 CI, 1.79- 3.84) for having at
    least 1 episode exceeding 1 year and 2.89 (95
    CI, 1.97-4.23) for meeting 6 or 7 dependence
    diagnostic criteria

Hingson et al., Arch Ped Adol Med 160739-746,
2006
33
Kaplan-Meier Survival Curves for Remaining Non
Alcohol Dependent Hingson et al., Arch Ped
Adol Med 160739-746, 2006
34
Risk for Alcohol Depend.AnytimeHingson et
al., Arch Ped Adol Med 160739-746, 2006
35
Risk for Alcohol Depend. in 10 Years Hingson
et al., Arch Ped Adol Med 160739-746, 2006
36
41,482 young men (18 to 20)
  • Marine Corps Recruit Depot, San Diego, Calif.
  • 6,128 (14.8) were identified as risky drinkers
  • 18,693 (45.1) as nonrisky drinkers
  • 16,661 (40.2) as nondrinkers
  • Risky Drinking
  • 5.5 fold odds if drinking onset lt14
  • ? Odds with
  • tobacco use, rural or small hometown, higher
    education, joined military for travel or
    adventure or to leave problems at home, numerous
    close friends and relatives, household alcohol
    abuse or mental illness, and childhood sexual or
    emotional abuse
  • Young et al., Arch Pediatr Adolesc Med.
    1601207-14, 2006

37
Conclusion
  • Public health efforts to decrease alcohol misuse
    may be effectively targeted by prevention of
    underage alcohol use, tobacco use, and childhood
    abuse.

38
Risk of Early Use May Be Linked to Brain
Development
39
Risk of Early Use May Be Linked to Brain
Development
  • Brain development is not complete until age 24,
    with key developmental milestones achieved while
    attending elementary and middle school (i.e., the
    same time as the high risk for establishing
    sustained use of alcohol, cigarette and drug
    use).
  • Support to children provided by their
    parents/families and other social systems can
    mitigate less fortunate genetic inheritance that
    regulate brain function.

40
Genetics
41
Social supports and serotonin transporter gene
moderate depression in maltreated children
  • Joan Kaufman , Bao-Zhu Yang , Heather Dougla
    Palumber, Shadi Houshyar , Deborah Lipschit, John
    H. Krystal , and Joel Gelernter
  • PNAS December 7, 2004 vol. 101 no. 49

42
Summary
  • In maltreated children, quality and availability
    of social supports s/s 5-HTTLPR allele moderate
    risk for depression
  • Maltreated children with the s/s genotype and no
    positive supports had 2 fold levels of depression
    compared to non-maltreated
  • Presence of positive supports reduced risk
    associated with maltreatment and the s/s
    genotype, such that maltreated children with this
    profile had only minimal increases in their
    depression scores.
  • Suggests that negative sequelae associated with
    early stress are not inevitable, esp. in context
    of supplied social support.

43
5-HTT gene affects the serotonin transporter
  • Two alleles (short and long) in 3 configurations
    s/s, s/l, l/l)
  • s/s conveys ? 5-HTT transcription, ? transporter
    levels and ? serotonin uptake
  • Shyness, behavioral inhibition
  • Anxiety, ? Negative emotions (e.g. fear),
    Depressed mood
  • ? susceptibility to stressful life events
    psychopathology

Kaufman et al., 2004
44
Kaufman et al., 2004
45
Serotonin Transporter Genetics and Social Support
vs. Maltreatment
Kaufman et al., 2004
46
Dopamine, Dominance Model
  • High Dopamine less interest in substance abuse
  • Low Dopamine high interest

47
DA2 Receptor Perception of Methylphenidate Dose
Volkow et al., 1999 Am J Psych 1999 156144043
48
Adolescent Brain Development and Drug Abuse
  • Ken C. Winters, Ph.D. Professor, Department of
    Psychiatry, University of Minnesota
  • A Special Report Commissioned by the Treatment
    Research Institute Philadelphia, P A., A Thomas
    McLellan, Executive Director

49
Clinical Questions Based on Brain Development
  • Do neurodevelopmental factors predispose
    adolescents to seek out and abuse alcohol and
    drugs?
  • Are there any deleterious effects on brain
    development as result of drug use in adolescence?

50
Adolescents Predisposed to seek out and abuse
alcohol and drugs?
  • Immature prefrontal cortex increases the
    propensity of teenagers to act impulsively and to
    ignore the negative consequences of such
    behavior.
  • Immature nucleus accumbens increases the
    adolescent's tendency to seek out activities that
    are exciting but require little effort.
  • Adolescents subjectively report greater feelings
    of social disinhibition when drinking alcohol
    compared to adults (Spear, 2002).

51
Adolescents Predisposed to seek out and abuse
alcohol and drugs?
  • Poor impulse control
  • Predisposed to favor low-effort yet thrilling
    experiences
  • Heightened sensitivity to the social benefits of
    intoxication

52
Brain Development
  • The brain continues through different phases of
    development across the life span.
  • Different brain areas develop at a varying rate.
  • Brain development is different between women and
    men and even different between identical twins.
  • Higher-order association cortices mature only
    after lower-order somatosensory and visual
    cortices, the functions of which they integrate,
    are developed.
  • Phylogenetically older brain areas mature earlier.

Lenroot and Giedd, 2006
53
Lenroot and Giedd, 2006
54
Brain Development Motor Skills
  • The Basal Ganglia loses up to 50 of Betz cells
    (involved in fine motor skills) between the ages
    7 and 11
  • This is evidence of long standing belief that
    practicing skills in the early development stages
    is essential to mastering technique (sports,
    music, etc.)

Giedd, 2003
55
Gender and Brain Development
  • Males
  • On average, the male brain is 10 larger than the
    female brain
  • Amygdala volume increases with age significantly
    only in males (high number of androgen receptors)
  • Females
  • Hippocampal volume increases significantly with
    age only in females (High number of estrogen
    receptors)
  • Caudate, and possibly globus pallidus and
    hippocampus, are disproportionately larger in
    female brains, whereas the amygdala is
    disproportionately smaller when compared to the
    brains of males.
  • (Giedd et al., 1996b)

Durston et al., 2006
56
Brain Development in Twins
  • Gyral and sulcal features of monozygotic twins
    are surprisingly dissimilar
  • May occur from differences in intrauterine events
    experienced by each of the twins
  • Supports model that brain development reflects
    both genetic and environmental factors Eckert et
    al., 2002

57
Brain Development Gender
  • By the age of 6, brain volume reaches
    approximately 95 of its peak volume
  • The brain volume of men peaks at 14.5 years
  • The brain volume of women peaks at 11.5 years

Giedd et al., 1999b
58
Cortical Development and Intelligence
  • Cortical thickness itself, is most closely
    related to level of intelligence.
  • - correlation between intelligence and cortical
    thickness in early childhood
  • correlation in late childhood and beyond
  • More intelligent children demonstrate a
    particularly plastic cortex, with an initial
    accelerated and prolonged phase of cortical
    increase, which yields to equally vigorous
    cortical thinning by early adolescence.

Shaw et al., 2006
59
Gogtay et al., 2004
Right lateral and top views of the dynamic
sequence of GM maturation over the cortical
surface. The side bar shows a color
representation in units of GM volume. Giedd, 1999
60
Attention Deficit Disorder
  • Boys and girls with ADD show smaller overall
    brain size
  • There are also abnormalities of the caudate
    nucleus evidenced by
  • A lack of normal asymmetry (decreased right-sided
    caudate volume)
  • Lesions on the caudate seems to lead to the
    emergence of secondary symptoms of ADHD

Castellano et al., 2006
61
ADD / ADHD Twin studies have confirmed
differential brain development
Castellano et al., 2006
62
Caudate NucleusVolume in ADHDCastellano et
al., 2006
63
Public Health Problem 3 Nicotine and probably
other select substances of abuse induce
significant semi-permanent to permanent changes
in the brain with even casual use.
64
Nicotine Dependence
65
a4ß2 nAChR
66
UpRegulation of Nicotine ReceptorValejo et
al., J. Neurosci., 25556372, 2005
67
Time Course of Nicotine Use StagesGervais et
al., CMAJ 175255-61, 2006
68
Time Course of Nicotine Use Stages
  • Inhalation 1.5 months (1.52.5)
  • Mental Addiction 2.5 months (1.52.5)
  • Smoking a whole cigarette 2.5 (1.03.0)
  • Cravings 4.5 (2.58.8)
  • Physical Addiction 5.4 (3.89.7)
  • Monthly Smoking 8.8 (7.011.9)
  • Withdrawal Symptoms 11.0 (6.416.8)
  • Tolerance 13.0 (10.320.5)
  • Weekly Smoking 19.4 (14.531.7)
  • Lifetime 100 cigarettes 19.5 (14.023.9)
  • Daily Smoking 23.1 (19.737.6)
  • Tobacco Dependence 40.6 (35.156.0)

69
Smoking and the Insula
  • There is evidence that lesions to the Insula can
    result in a disruption in smoking addictions as
    measured by
  • Reporting quitting smoking less than 1 day after
    lesion onset
  • Reporting that they did not start smoking again
    after they quit
  • Rating the difficulty of quitting as less than
    three on a scale of one to seven
  • Reporting feeling no urges to smoke since
    quitting

Naqvi, et al., 2007
70
Patients with Brain Lesions in Insula Lost All
Desire to Smoke
Naqvi, et al., 2007
71
Smoking and the Insula
  • This study found that people with a lesion on the
    Insula reported less urges to smoke after the
    lesion and fewer smoked cigarettes after the
    initial abstention
  • It has also been shown that a high amount of
    activity in the right insula during a simple
    decision-making task is associated with relapse
    to drug use
  • These results imply that therapies that modulate
    the function of the insula will be useful in
    helping smokers quit.

Naqvi, et al., 2007
72
Brain Risk Model for Prevention of Alcohol, Drugs
and Cigarette Use in Children and Adolescents
  • ?Risk / ?Risk Model

73
Risk-Based Prevention Model
74
Other Use Patterns
75
Resilience Links
  • Trauma History
  • Stress Reduction System
  • Social Support
  • Genetics
  • Parent/Fam. Supervision
  • Family/Peers Use
  • Availability of Alc/Drugs/Cigs
  • Links to stress reduction
  • Links to brain develop.
  • Links to stress reduction
  • Long allele 5HT transporter
  • Usually across-the-board availability though
    affluence increases availability

76
Goals of Presentation
  • Describe 3 major public health problems with
    substance use in children and adolescents
  • Describe brain mechanisms that may contribute to
    these 3 major public health substance use
    problems
  • Discuss overall risk model for prevention of
    alcohol, drugs and cigarette use in children and
    adolescents with specific focus on brain
    development and genetics

77
Learning Objectives
  • 1. At the completion of this presentation, the
    attendee will be able to describe key age windows
    of risk for substance use by children and
    adolescents and their relationship to stages of
    brain development.
  • 2. At the completion of this presentation, the
    attendee will be able to describe where addiction
    is manifested in select areas of the brain
    including the prefrontal cortex.

78
Learning Objectives
  • 3. At the completion of this presentation, the
    attendee will be able to describe strategies for
    prevention of substance abuse in children and
    adolescents based on lessions from the brain
    sciences.
Write a Comment
User Comments (0)
About PowerShow.com