Neurobiology of Adolescent Substance Abuse from a Developmental - PowerPoint PPT Presentation

Neurobiology of Adolescent Substance Abuse from a Developmental Perspective Deborah R. Simkin, M.D. Clinical Assistant Professor Department of Psychiatry University of Emory School of Medicine 1

Disclosures • Pfizer Inc. Research Support

Learning Objectives • Scope of the problem • Developmental vulnerability

Narcotics other than Heroin: Trends in Annual Use and Availability Grades 8, 10, and 12 Source. The Monitoring the Future study, the University of Michigan.

Narcotics other than Heroin: Trends in Annual Use and Availability Grades 8, 10, and 12 Source. The Monitoring the Future study, the University of Michigan.

Scope of the Problem Domains of Factors Associated with Drug Use (Newcomb, 1997) I. Cultural/Societal – Laws favorable to drug use – Social norms favorable to drug use – Availability of drugs – Extreme economic deprivations – Neighborhood disorganization

Protective Factors – RESILENCE - Good life events and an internal locus of control seem to cushion the development of substance use disorders in sons of alcoholics (Springer, '95) – stable environment – high degree of motivation – strong parent-child bond consistent parental supervision & discipline – bonding to pro-social institution – association with peers who hold conventional attitudes – consistent community wide anti-drug use messages (Glantz, '98)

Scope of the Problem Newcomb, 1997 Child and Adolescent Psychobehavioral Influences • Age of first use-higher % of those who start <11 yo met criteria for dependence than those that start 14- 15 yo • Rapid progression of SUD occurred with earlier onset & frequency and not duration of use of substances (DeWitt, ’00, Kandel ’92) • Earlier onset had shorter time span between 1 st exposure to dependence than adult onset groups (Clark,’98)

Scope of the problem • ALCOHOL • Event Age • First drink- 13 • First drunk -15 • First problem -18 • First dependence -25-40 • Death -60 • (Schukit, 2000) • Therefore, Addiction is a pediatric disease

Developmental Vulnerability

• family • history Pre school Kindergarten- 5 th grade middle school high school • MJH & • drinks q d • age birth 3-5 5-7 8- 9-10 11-14 15----- 16-17--18__ • events: -Pare nts separate -Parents • Pre-natal -Separation -Untreated -Sexual abuse separate - • exposure anxiety ADHD by neighbor again - raped nicotine and LD while • and drunk • MJH l -Driving while • -Hypoxia at birth -Po or grades intoxicated • -Poor nutrition co ntinue - Stops soccer • -Cigarette use begins -Begins using • marijuana and alcohol • and loratab in mom’s • medicine cabinet

Neurobiological insults that increase risk for substance abuse from developmental perspective as seen in case example above 1. Family history - Mom (depression), Mat Uncle PTSD died of cirrhosis, Pat GP and Dad alcoholics. (Cadoret, RJ, etal, Arch of Gen Psychiatry 1986. Kendler, KS, Presscott, CA. Amer. J. Psychiatry 1998) -Lower D2 receptors in NaC, seen in families with alcoholism, decreases ability to inhibit drive to use drugs 2. Prenatal nicotine exposure -increased toddler negativity, -increased externalizing disorders such as, ADHD or ADHD symptoms and/or conduct disorders -lower IQ and auditory functions (Niaura, J, et al, Amer J of Addic , 2001. Weissman, MM, et al, JAACP , 1999) 3. Prenatal exposure to MJH- -visual working memory deficits -inattention -short term memory deficits (Day, N, et al, ADDICTION , 2006. Goldschmidt, L, et al, JAACP 2008. Smith AM, et al, Neurotoxicol Terato, 2006 .)

What causes Adolescents to experiment-role of early development of the Pre Frontal Cortex • Casey, et al 2008

Neurobiological insults that increase risk for substance abuse from developmental perspective 4. Hypoxia and nutritional deficits= – increased risk for ADHD and LD (Stein, MB, et al. Neuropsychopharm, 2008. Levenson, JM, Nat Rev Neurosci . 2005. Koob G & LeMoal M, Annual Rev Psychol , 2008) Note: for examples # 2, 3 and 4, – Substance abuse at age 14 or 15 could be predicted by academic and social behavior between the ages of 7 and 9 (Hyman Hops, et al, J Study Alcohol Suppl. 1999) – Adolescents with attention difficulties not associated with ADHD but with undiagnosed LD’s, predicted substance abuse and dependence eight years later. (Tapert, SF, et al, JAACAP, 2002)

Neurobiological insults that increase risk for substance abuse from developmental perspective 5. 2006-2008 National Survey on Drug Use and Health. (Fiellin, et al, J Adol Health, 2013) • RESULTS: • Twelve percent of the survey population of 18-25 year olds (n = 6,496) reported current abuse of prescription opioids. • For this population, prevalence of previous substance use was 57% for alcohol, 56% for cigarettes, and 34% for marijuana. • Among both men and women, previous marijuana use was 2.5 times more likely than no previous marijuana to be associated with subsequent abuse of prescription opioids. • Previous alcohol, cigarette, and marijuana use were each associated with current abuse of prescription opioids in 18-25- year-old men, but only marijuana use was associated with subsequent abuse of prescription opioids in young women.

Neurobiological insults that increase risk for substance abuse from developmental perspective 6. Disturbed brain connectivity in cannabis users may underlie cognitive impairment and vulnerability to psychosis, depression and anxiety disorders (Lim, et al, 2002) and cognitive function (Meier, 2012) A. White matter alterations have been associated with various functional and clinical outcomes in schizophrenia, including illness, symptomatic and cognitive measures (Walterfang et al, 2011). B. White matter pathology underlying faulty integration of cortical – cerebellar – thalamic – cortical circuits are thought to play a primary role in the observed cognitive deficits (Wexler et al, 2009)

The right fimbria of the hippocampus, hippocampal commissure and splenium comprised fewer streamlines in cannabis users compared to non-users (P < 0.05, corrected). 2 different oblique views. Red areas denote fewer streamlines Zalesky A et al. Brain 2012;135:2245-2255

Neurobiological insults that increase risk for substance abuse from developmental perspective C. Similar connectivity disturbances, particularly in the fimbria of the hippocampus and commissural fibres extending to the precuneus have been reported in a study (Zalesky, 2012). • The hippocampus appears to have the highest density of CB1 receptors. • This may underlie the memory impairment and other cognitive deficits that are observed in long-term heavy cannabis users.

Fewer streamlines interconnected the right precuneus with the splenium in cannabis users compared to non-users (P < 0.05, corrected). Zalesky A et al. Brain 2012;135:2245-2255

Neurobiological insults that increase risk for substance abuse from developmental perspective C. Long term use and effect on IQ (Meier, et al, 2012) • Association between persistent cannabis use — prospectively assessed over 20 y — and neuropsychological functioning in a birth cohort of 1,037 individuals. • Study members underwent neuropsychological testing at age 13 y before the onset of cannabis use and again at age 38 y, after some had developed a persistent pattern of cannabis use. • Cannabis use was ascertained in interviews at ages 18, 21, 26, 32, and 38 y. • Findings:

Neurobiological insults that increase risk for substance abuse from developmental perspective Findings: 1. More persistent cannabis users did show greater IQ decline, with the most persistent users ( n = 41) losing an average of 5 – 6 IQ points from age 13 y to 38 y 2. Persistent cannabis users showed neuropsychological decline across five different areas of mental function (executive functions, memory, processing speed, perceptual reasoning, and verbal comprehension), indicating that decline is global. • Furthermore, this decline was still apparent after controlling for years of education • and after ruling out multiple other alternative explanations (for example, the decline was not due to persistent dependence on alcohol or other substances).