Alcohol and the adolescent brain: Why delaying the onset of drinking is so important

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1 Alcohol and the adolescent brain: Why delaying the onset of drinking is so important Aaron White, PhD Division of Epidemiology and Prevention Research National Institute on Alcohol Abuse and Alcoholism National Institutes of Health Youth drinking is a global concern Alcohol: Binge by 8 th, 10 th, 12 th graders Binge = 5+ drinks at a time at least once in a two week period Significant decline for all grade levels Source: Monitoring the Future (2012) MTF,

2 Alcohol: Binge by gender (12 th grade) % Percent % 27% 20% MTF, Male Female Percent of 12 th grade males and females who binge once or more per 2 wks Source: Monitoring the Future (2012) U.S. teens compared to other countries Questions: What is it about adolescence that increases the likelihood of excessive drinking during this stage of life? How do the effects of alcohol on the adolescent brain help explain the short-term and long-term consequences of alcohol use? What do the findings suggest for prevention strategies? 2

3 A Winter s Tale (Shakespeare, 1623) I would there were no age betweene ten and three and twenty, or that youth would sleep out the reste for there is nothing (in the betweene) but getting wenches with childe, wronging the Auncientry, stealing, fighting. (III.iii.59-63) What is adolescence? Collection of changes that help prepare one to survive with relative independence - Increase in time with peers - Increase in risk taking/novelty seeking - Increase in family conflicts Roughly second decade of life (WHO, 2008) Widespread brain changes shift control of behavior from emotion to cognition Overlaps with puberty but not the same Alcohol use often begins here Adolescent brain development Frontalization of function Frontal lobes take on more and more organizational control over behavior as adolescence unfolds 3

4 N A N A V P V T A Frontal lobe remodeling Planning, decision-making, impulse control, memory, language and more Remodeled during adolescence Feeling good - Hedonic Hot Spots NA N A V P V T A VP VTA Liking Part of the feeling of pleasure. Involves opioid and endocannabinoid receptors in and around the Nucleus Accumbens (NA) and Ventral Palladium (VP). Activated by natural reinforcers and by substances. Activation reinforces the behavior that lead to it. Wanting Part of the drive for something associated with pleasure. Involves dopamine from Ventral Tegmental Area (VTA) to Nucleus Accumbens (NA). Activated naturally and by various drugs. Activation facilitates learning about stimuli associated with pleasure. Pecina et al. Hedonic hot spots in the brain. The Neuroscientist, 2006;12(6), Changes in the reward system The reward system helps shape behavior by providing reinforcement when something presumably good for survival is done (e.g., eating food, drinking fluids, social bonding, sex, etc.) Both the VTA and NA also send signals to the frontal lobes increasing attention so that the brain can learn about and remember what triggered the reinforcement. Nucleus accumbens VTA 4

5 Reward system activation, reinforcement and learning Natural Rewards Elevate Dopamine Levels % of Basal DA Output Empty 50 Box Feeding 0 FOOD NAc shell Time (min) Di Chiara et al., Neuroscience, DA Concentration (% Baseline) Sample Number SEX Female Present Fiorino and Phillips, J. Neuroscience, Copulation Frequency Mounts Intromissions Ejaculations NIDA Addiction slides % of Basal Release Effects of Drugs on Dopamine Release % of Basal Release Accumbens AMPHETAMINE DA DOPAC HVA hr Time After Amphetamine hr Time After Nicotine NICOTINE Accumbens Caudate % of Basal Release % of Basal Release Accumbens COCAINE DA DOPAC HVA hr Time After Cocaine Accumbens MORPHINE Dose (mg/kg) hr Time After Morphine Di Chiara and Imperato, PNAS, 1988 NIDA Addiction slides 5

6 Reward (monetary) activates ventral striatum more strongly in adolescents than children or adults Same is seen in anticipation of reward FIGURE 3. Ventral striatal activity to reward and association with risk-taking. Note: Ventral striatum (left) is activated with reward (middle) and correlated with risk-taking (right) (adapted from Galvan et al. 6 and Galvan et al. 16 ). Such findings could mean that adolescents are more motivated for reward and more reinforced by it. SOURCE: Casey BJ, Jones RM. Neurobiology of the adolescent brain and behavior: implications for substance use disorders. J Am Acad Child Adolesc Psychiatry Dec;49(12): ; Peers increase adolescent risk taking by enhancing activity in the brain s reward system When friend is in the room during driving task, teen males show: Normal LPFC Decision making, impulse control Elevated VS Reinforcement/ attention Elevated OFC Making sense of social cues and integrating with behavior SOURCE: Chein et al. (2010). Peers increase adolescent risk taking by enhancing activity in the brain s reward system. Dev Sci F1-F10 Stressed out teenagers Adolescent amygdala highly reactive to stressful stimuli Stress hormone (cortisol) levels higher during adolescence Adolescence is a time of high stress and uncertainty Amygdala Volume knob for fear and anxiety Allows for learning to fear things Allows for learning not to fear things 6

7 Adolescent brains built to learn Hippocampus creates memories for facts and events Severe damage here leads to permanent amnesia for events that occur after the damage Hippocampus Memories for facts and events Birth of new brain cells peaks here in adolescence During adolescence strong drives and still developing cognitive control contributes to risk-taking FIGURE 1. Cartoon model of ventral striatal cortex and prefrontal cortex (PFC) interactions across development. Note: Deeper color indicates greater regional signaling. Line represents functional connectivity, with solid line indicating mature connection and dotted line indicating immaturity. SOURCE: Casey BJ, Jones RM. Neurobiology of the adolescent brain and behavior: implications for substance use disorders. J Am Acad Child Adolesc Psychiatry Dec;49(12): ; Adolescence is risky business Alcohol and drug use often begins here Romer et al.,

8 Alcohol and other drugs can turn adaptive tendencies into maladaptive behaviors Adolescent brains built to learn with ease with an eye toward success during adulthood Adolescent brains learn particularly fast when behaviors are rewarded Frontal lobes (decision-making, impulse control) are not fully online during adolescence but emotional drive is in high gear Alcohol and other drugs produce reward leading to rapid learning and motivating further use Alcohol causes both short-term and long-term effects that are bad for adolescents Alcohol increases risk taking and impairs decision-making Alcohol suppresses the frontal lobes, which are responsible for decision-making, planning and impulse control Alcohol Suppresses frontal lobes Leads to poor decision making and risky behaviors Acute intoxication impairs executive function and disrupts frontal lobe activity BAC = 0.00% BAC = 0.05% BAC = 0.10% Alcohol increased reaction time and false alarm errors in a dose-dependent manner in a Go/No-Go task (N = 51, mean age 24.5). FMRI analyses showed alcohol decreased activity in anterior cingulate, lateral prefrontal cortex, insula and parietal lobe regions during false alarm responses to No-Go stimuli. Anderson et al. (2011). Imaging of Cognitive Control During Acute Alcohol Intoxication Alcohol Clin Exp Res. 35(1):

9 Cognitive impairments in alcohol dependent teens three weeks into inpatient treatment Source: Tapert, Delis and Granholm, 2000 Relationship between levels of alcohol and marijuana use and measures of cognitive function in adolescents As the number of drinks consumed per day goes up performance on tests of attention, executive function and memory go down. More days smoking marijuana equals poorer memory. SUBJECTS: 48 adolescents (ages 12 to 18), recruited in 3 groups: a healthy control group (HC, n = 15), a group diagnosed with substance abuse or dependence (SUD, n = 19), and a group with a family history positive for alcohol use disorder (AUD) but no personal substance use disorder (FHP, n = 14). RESULTS: More DPDD predicted poorer performance on Attention and Executive Function composites, and more frequent use of marijuana was associated with poorer Memory performance. In separate analyses, adolescents in the SUD group had lower scores on Attention, Memory, and Processing Speed composites, and FHP adolescents had poorer Visuospatial Ability. Thoma et al. (2011), Adolescent Substance Abuse: The Effects of Alcohol and Marijuana on Neuropsychological Performance. Alcoholism: Clinical and Experimental Research, 35: Heavy drinking during adolescence associated with reduced frontal lobe volume Ventral Prefrontal Volume Prefrontal cortex: Dorsal Posterior Non-drinker Girls Heavy Drinking Girls Ventral Source: Squeglia et al.,

10 Binge drinking during adolescence linked to disrupted white matter tracts connecting brain areas Binge drinking teens (N = 14, age 16-19, average 15 drinks per month) with no history of alcohol use disorders had lower FA than controls (N = 14, age 16-19) in 18 white matter areas including the corpus callosum (above). Lower FA in 6 areas was linked to significantly greater lifetime hangover symptoms and/or higher estimated peak blood alcohol concentrations. McQueeny et al., 2009, ACER Frontal lobe activity at baseline predicts transition to heavy drinking in teens Differences in BOLD response during no-go trials at baseline between adolescents who transitioned into heavy alcohol use (TU; n=21) versus controls (CON; n=17). Areas in blue indicate where future users had significantly less BOLD response during inhibition (no-go) trials relative to baseline than non-users (p<.01, clusters >864 μl). In no region did TU show more no-go response than CON. Norman et al. Drug Alcohol Depend December 15; 119(3): Alcohol Shot of courage By suppressing the amygdala alcohol diminishes psychological experiences of stress (fear and anxiety) Does not help with the physiological effects of stress Makes it easier to do risky things Alcohol Quiets the amygdala Temporary reduction in experience of stress 10

11 Alcohol suppresses amygdala response to threatening stimuli FIGURE. Alcohol effects on amygdala activation to social signals of threat. A) Right lateral amygdala activation to Threat (> Nonthreat) faces is present during the PBO session but absent during the ALC session. B) Mean BOLD Response (β weights ±SEM) extracted from amygdala ROIs showing activation to Threat (> Non-threat) faces in the PBO session but no activation during the ALC session. PBO, placebo; ALC, alcohol. C) Mean BOLD Response showing alcohol attenuates (PBO>ALC) activation to Threat (Angry, Fearful) faces but does not affect responses to Non-threat (Happy Faces). Source: Sripada et al., 2011, Neuroimage, 55, Alcohol produces reward Alcohol activates the reward system, which exists to pat us on the back when we do something good for survival Alcohol Activates the reward system Makes brain think something important just happened Adolescent alcohol abusers show strong reactions to alcohol-related cues reflecting strong associative learning Functional magnetic resonance imaging (fmri) results during alcoholic beverage picture trials relative to non-alcoholic beverage picture trials Greater activation in AUD subjects (red color) in the ventral anterior cingulate and subcallosal, prefrontal, orbital, and limbic regions, areas previously associated with reward and drug craving. AUD group (N = 15) 6 girls 9 boys average age of 16, DSM abuse or dependence Control group (N = 15) 6 girls 9 boys average age 16, low levels of previous use Tapert, Susan. F. et al. Arch Gen Psychiatry 2003;60:

12 Amount of brain activation in response to alcoholrelated cues increases with drinking levels Tapert, Susan. F. et al. Arch Gen Psychiatry 2003;60: Blood oxygen level-dependent (BOLD) response signal contrast in the right precuneus/posterior cingulate region during exposure to alcoholic beverage pictures relative to nonalcoholic beverage pictures plotted as a function of drinks consumed per month for adolescents with alcohol use disorder (n = 15) Are strong associations between alcohol and cues part of why adolescents are at such high risk of developing dependence and of relapsing? Age of drinking onset and dependence: Risk goes up as age goes down AGE FHP (%) FHN (%) Source: Grant and Dawson, 1997 Alcohol blocks new memories Alcohol disrupts activity of memory circuits in hippocampus Laboratory studies (rats) show the hippocampus is more sensitive to alcohol during adolescence than adulthood Hippocampus Alcohol blocks functioning Can lead to amnesia if dose is high enough 12

13 Alcohol-induced memory blackouts 13

14 Memory blackouts are common % Prevalence of blackouts in a sample of U.S. college students (n = 772) 51% 12% of students who drank in twoweek period over summer between HS graduation and college 40% 9% LIFETIME YEAR 2 WKS Source: White et al, 2002, American Journal of College Health Source: White et al, 2002, American Journal of College Health Alcohol can cause death directly Excessive consumption of alcohol shuts down areas of the brainstem involved in vital functions like breathing, gagging, and heart rate Alcohol Suppresses respiratory areas and other vital reflex centers Causes death 14

15 Alcohol overdose Alcohol overdose/poisoning Alcohol has a very small therapeutic index (TD 50 /ED 50 ) A toxic or deadly dose not much higher than a moderately intoxicating dose Potentially fatal alcohol overdoses: How much alcohol? If ED 50 = ~.05% And TD 50 = ~.35% Then TI = ~7 10 drinks in 2 hrs for a 140 lb female 13 drinks in 2 hrs for a 160 lb male Posted 10/7/2004 Five binge-drinking deaths 'just the tip of the iceberg' By Robert Davis, USA TODAY This month has been deadly for binge-drinking college students. Five underclassmen in four states appear to have drunk themselves to death, police say, after friends sent their pals to bed assuming that they would "sleep it off." 15

16 67% increase in hospitalizations for alcohol overdoses among youth between ~ ½ alcohol only (up 25%) ~ ½ alcohol + other drugs (up 76%) Source: White et al., 2011 Poisoning deaths outnumber traffic crash deaths What can be done? Interventions that focus on Individuals Families Schools Communities Providing and encouraging alternatives Modeling healthy alcohol use Given association between early use and dependence, delaying onset critical 16

17 Common question: Should parents allow teens to drink at home? Several studies in the US and other countries suggest that allowing teens to drink at home, either with parents or supervised by parents, increases the odds that a teen will binge drink outside of the home. (McMorris et al J Stud Alcohol Drugs, 72(3), ) Where do underage drinkers drink? Drinking Locations by Age Group, 12-20: (SAMHSA, CBHSQ, NSDUH, special data analysis, 2010) Source: SAMHSA Report to Congress on Prevention and Reduction of Underage Drinking, May 2011 Summary Alcohol is risky for adolescents in part because the brain is still developing Alcohol causes direct effects on adolescent brain that increase risk of accidents and bad decision-making Long-term lingering effects on brain including heightened risk of alcoholism and cognitive deficits Goal should be to delay onset and model healthy use 17

18 NIAAA Resources (niaaa.nih.gov) Aaron White, PhD National Institute on Alcohol Abuse and Alcoholism 5635 Fishers Lane, Room 2094 Bethesda, MD Phone: THANK YOU! 18