HELLO AND WELCOME TO THE NIAAA 50TH ANNIVERSARY SCIENCE SYMPOSIUM. A PROGRAM WE HAVE DEVELOPED IN HONOR OF THIS IMPORTANT MILESTONE IN OUR INSTITUTE'S HISTORY. TODAY WE ARE CELEBRATING 50 YEARS OF PROGRESS IN THE RESEARCH ON THE CAUSES AND CONSEQUENCES OF ALCOHOL MISUSE, INCLUDING EVIDENCE-BASED ADVANCES IN THE DIAGNOSIS, PREVENTION AND TREATMENT OF ALCOHOL USE DISORDER AND ALCOHOL-RELATED PROBLEMS. TO COMMEMORATE THIS ACCOMPLISHMENT, OUR SPECIAL SYMPOSIUM ENTITLED ALCOHOL ACROSS THE LIFESPAN: 50 YEARS OF EVIDENCE-BASED DIAGNOSIS, PREVENTION AND TREATMENT RESEARCH, WILL FEATURE PRESENTATIONS BY LEADING RESEARCH EXPERTS WHO WILL DISCUSS RESEARCH ADVANCES ACROSS MANY DOMAINS IN ALCOHOL RESEARCH. AND THE OPPORTUNITIES THAT LIE AHEAD. I WOULD LIKE TO THANK ALL THE EXPERTS WHO ENTHUSIASTICALLY ACCEPTED MY INVITATION TO SPEAK WITH US DURING THIS SYMPOSIUM. IT WAS A LOT OF WORK FOR ALL OF THEM, AND I REALLY, REALLY AM GRATEFUL. AND BEFORE WE GO ON, I WOULD LIKE TO MENTION A FEW HOUSEKEEPING DETAILS AND ITEMS. WE WILL HOST A LIVE QUESTION AND ANSWER SESSION AFTER EACH LECTURE. THERE WILL BE -- ON THE NIH VIDEOCAST PAGE AND THE EVENTS PAGE ON THE NIAAA WEBSITE. NIAAA'S 50TH ANNIVERSARY IS TRULY A MILESTONE IN THE HISTORY OF PUBLIC HEALTH. FIVE DECADES AGO, A GROUP OF RESEARHERS MADE THE FAR-SIGHTED DECISION WHEN THEY PUSHED FOR THE CREATION OF THE NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM. A COMPREHENSIVE ALCOHOL ABUSE AND ALCOHOLISM PREVENTION TREATMENT AND REHABILITATION LAUNCHED NIAAA, AUTHORIZING TO DEVELOP AND CONDUCT COMPREHENSIVE HEALTH, EDUCATION, TRAINING, RESEARCH AND PLANNING PROGRAMS FOR THE PREVENTION AND TREATMENT OF ALCOHOL-RELATED PROBLEMS, UNQUOTE. A FEDERALLY FUNDED AGENCY TO PLAN AND SUPPORT ADVANCES IN A VARIETY OF DOMAINS AND FROM ALCOHOL'S EFFECTS ON THE DEVELOPING ADOLESCENT BRAIN TO ALCOHOL USE DISORDER. IMPORTANTLY, IT ALSO HELPED US TO CHANGE THE WAY WE VIEW THE MISUSE OF ALCOHOL AND ALCOHOL USE DISORDER. IT HELPED US TO UNDERSTAND THAT ALCOHOL USE DISORDER IS A CHRONIC HEALTH CONDITION, NOT A MORAL FAILING. NIAAA IS NOW THE WORLD'S LARGEST FUNDER OF ALCOHOL RESEARCH, WITH A MISSION OF IMPROVING DIAGNOSIS, PREVENTION, AND TREATMENT OF ALCOHOL USE DISORDER AND OTHER ALCOHOL-RELATED PROBLEMS ACROSS THE LIFESPAN. WITH OUR BROAD RESEARCH PORTFOLIO, NIAAA'S WORK FOCUSES ON HEALTH TOPICS THAT TOUCH THE LIVES OF ALMOST EVERY FAMILY AND COMMUNITY ACROSS THE UNITED STATES. TODAY THANKS OF OUR LEGACY OF INNOVATIVE RESEARCH, WE KNOW HOR ABOUT ALCOHOL EFFECTS ON THE BRAIN AND BODY ACROSS THE LIFESPAN THAN EVER BEFORE, AND WE HAVE EVIDENCE-BASED INTERVENTIONS TO PREVENT AND TREAT ALCOHOL MISUSE. AND WE'VE MADE PROGRESS IN MANY AREAS, FROM UNDERAGE DRINKING TO FETAL ALCOHOL SPECTRUM DISORDER TO -- DEVELOPMENT. I'M ALSO MINDFUL OF OUR WORK AHEAD EVEN AS WE FACE NEW AND DAUNTING CHALLENGES IN DEPTHS OF DESPAIR, THE COVID-19 PANDEMIC AND THE STRESS ASSOCIATED WITH THESE CHALLENGES. SO I THINK IT IS FITTING TO OPEN THIS SCIENTIFIC SYMPOSIUM WITH AN OVERVIEW ABOUT THE CHALLENGES FACING ALCOHOL RESEARCH AND IN PARTICULAR, THE MISUSE OF ALCOHOL AS A COPING RESPONSE IN THE CONTEXT OF HYPERKATIFEIA, DEATHS OF DESPAIR AND COVID-19. I JUST WANT TO ADD ONE OTHER THING, AND THAT IS THAT -- NIAAA AND I'M VERY PROUD TO HAVE BEEN THE DIRECTOR FOR SEVEN OF THOSE 50 YEARS, AND I'M LOOKING FORWARD TO A GREAT FUTURE WITH NIAAA -- CHALLENGES AND PRIORITIES. I CAN'T EMPHASIZE ENOUGH THE SCOPE OF THE PROBLEM WITH ALCOHOL. I ALWAYS LIKE TO COMPARE TO THE OPIOID CRISIS AND THERE IS, OF COURSE, A VERY REAL -- UP TO 95,000 -- BUT I THINK YOU CAN SEE THAT ALCOHOL IS, AS I OFTEN SAY, ADDICTION THAT EVERYONE KNOWS ABOUT BUT NO ONE WANTS TO TALK ABOUT. SO ALCOHOL USE DISORDER OVER THE PAST FEW YEARS, THERE HAVE BEEN A NUMBER OF CONCEPTUAL ADVANCES, AND NOTABLY OVER THE PAST A DEVELOPMENTAL DISORDER THAT VARIES ACROSS THE LIFESPAN AND BY INDIVIDUAL, A BRAIN DISORDER THAT CAN BE STUDIED THROUGH A HEURISTIC FRAMEWORK THAT'S BOTH PREVENTABLE AND TREATABLE. RECOVERY FROM ALCOHOL USE DISORDER IS ATTAINABLE BUT OFTEN INCLUDES RELAPSE AS PART OF THE PROCESS. AND ALCOHOL FITS WITHIN THIS CYCLE, THE THREE STAGES ARE COLOR-CODED WITH REGIONS OF THE BRAIN IF AFFECT WITH AFFECT ANDWITHDRAWAL -- AMYGDALA -- STRESS AND A REDUCTION IN REWARD THAT'S ASSOCIATED WITH THE NEGATIVE AFFECT WITHDRAWAL STAGE, AND THEN, OF COURSE, THE CRAVING DOMAIN, WHICH IS GREEN AND ILLUSTRATES FRONTAL CORTEX -- AND PREOCCUPATION -- CYCLE. -- HIGHLIGHT A FEW ADVANCES OF THE LAST 50 YEARS IN EPIDEMIOLOGICAL RESEARCH HAS ENABLED US TO TRACK PROGRESS AND CHANNEL CHALLENGES ASSOCIATED WITH ALCOHOL MISUSE IN THE UNITED STATES. WE'RE GOING TO HEAR MORE FROM KATHERINE KEYES TODAY AT 1:20 P.M., ADVANCES IN UNDERSTANDING THE GENETICS OF ALCOHOL USE DISORDER HAVE IMPLICATIONS FOR PREVENTION AND PRECISION MEDICINE, WE'LL HEAR MORE FROM MARC SCHUCKIT TODAY AT 2:20 P.M. RESEARCH HAS ESTABLISHED THAT THE ADOLESCENT BRAIN IS UNIQUELY VULNERABLE TO THE EFFECTS OF ALCOHOL, LONGITUDAL STUDIES THAT ASSESS PREDICTORS AND CONSEQUENCES OF ADOLESCENT ALCOHOL CONSUMPTION CONTINUE TO INFORM PREVENTION AND TREATMENT STRATEGIES. WE'LL HEAR MORE FROM SUSAN TAPERT TODAY AT 3:20 P.M. TOMORROW WE'LL HEAR MORE ABOUT THE STRESS NEUROBIOLOGY IN ALCOHOL MISUSE HAS IMPLICATIONS FOR RISK AND RECOVERY FROM ALCOHOL USE DISORDER, WE'LL HEAR MORE FROM RAJITA SINHA TOMORROW, AND IN ADDITION TO A MENU OF BEHAVIORAL THERAPIES, THERE ARE CURRENTLY THREE FDA-APPROVED MEDICATIONS FOR TREATMENT, WE'LL HEAR MORE ABOUT THAT FROM BARBARA MASON TOMORROW AT 2:05 P.M. RECOGNIZED BY RESEARCHERS IN THE 1970s, FETAL ALCOHOL SPECTRUM DISORDER HAS BEEN A LONG-STANDING RESEARCH PRIORITY FOR NIAAA. WE'LL HEAR MORE ABOUT THAT FROM MICHAEL CHARNESS, AND SOME OF THE GREAT ADVANCES IN THIS AREA FROM MICHAEL CHARNESS TOMORROW AT 3:20 P.M., AND AS ALCOHOL-ASSOCIATED LIVER DISEASE CONTRIBUTES TO INCREASING ALCOHOL-RELATED MORTALITY, TREATMENT REMAINS AN UNMET CLINICAL NEED, WE'LL HEAR MORE ABOUT THAT FROM VIJAY SHAH TOMORROW AT 4:20 P.M. SO JUST A COUPLE OF CHALLENGES AND PRIORITIES THAT WE FACE AT THE INSTITUTE THAT I SEE INTO THE FUTURE. ALCOHOL AND CO-OCCURRING CONDITIONS, MENTAL HEALTH CONDITIONS, ALCOHOL MISUSE OFTEN PRECEDES DIAGNOSES IN AN EFFORT TO COPE WITH SYMPTOMS, EACH CONDITION EXACERBATES THE OTHER. PAIN, ACUTE ALCOHOL AT BINGE LEVELS MAY REDUCE PAIN BUT CHRONIC ALCOHOL AND WITHDRAWAL INCREASE PAIN SENSITIVITY, DISRUPTED SLEEP, PERSISTENT SLEEP PROBLEMS DURING ABSTINENCE PROMOTE RELAPSE AND ARE A MAJOR IMPEDIMENT FOR RECOVERY FROM ALCOHOL USE DISORDER. THEN EMERGING TRENDS FROM ALCOHOL USE IN THE POPULATION, ALCOHOL USE AMONG WOMEN, GENDER GAPS ARE NARROWING FOR PREVALENCE, EARLY ONSET DRINKING, FREQUENCY AND INTENSITY OF DRINKING. INCREASING ALCOHOL USE AMONG SENIOR ADULTS, 65 AND OLDER, 1 IN 10 ENGAGE IN BRING DRINKING. THESE ARE CHALLENGES WE FACE IN THE FUTURE. A BIG CHALLENGE IS CLOSING THE TREATMENT GAP. IN THE U.S., FEWER THAN 10% OF PEOPLE RECEIVE ANY FORM OF TREATMENT, ROUTINE HEALTHCARE PRESENTS A UNIQUE OPPORTUNITY FOR PREVENTION, EARLY INTERVENTION AND TREATMENT. HOWEVER, MANY HEALTHCARE PROVIDERS DO NOT PERFORM ALCOHOL SCREENING, OUR GOALS ARE TO IMPROVE PHYSICIAN TRAINING IN SUBSTANCE MISUSE PREVENTION AND TREATMENT AT ALL LEVELS AND TO INTEGRATE PREVENTION, EARLY INTERVENTION AND TREATMENT INTO ROUTINE HEALTHCARE. AND FINALLY AN AREA WE'RE CURRENTLY ENGAGED IN S I HOPE WE BRING TO FRUITION IN THE NEAR FUTURE, TWO PIECES THAT I THINK WILL CONTINUE TO CLOSE THE GAP, DEVELOPING A CLINICIAN'S CORY SOURCE. FROM PHARMACISTS TO NURSE PRACTITIONERS TO PHYSICIANS' ASSISTANTS TO PRIMARY CARE DOCTORS TO BOARD CERTIFIED ADDICTION SPECIALISTS, BASIC INFORMATION ABOUT ALCOHOL THAT EVERY CLINICIAN SHOULD KNOW. YOU CAN SEE THE LIST HERE OF THINGS THEY INCLUDE, PRESENTATION IN PRIMARY CARE, ROLE IN COMMON CO-OCCURRING CONDITIONS, DIAGNOSTIC CRITERIA, RECOMMENDED DRINKING LIMITS, EVIDENCE-BASED THERAPIES/MEDICATIONS, ADDRESSING STIGMA AND INTERACTIONS WITH COMMONLY USED MEDICATION. IN ADDITION, WE WANT TO SUPPORT RESEARCH ON RECOVERY FROM ALCOHOL USE DISORDER. FOR CONSISTENCY ACROSS RECOVERY RESEARCH STUDIES, NIAAA ENGAGED STAKEHOLDERS TO DEVELOP A CONSENSUS RESEARCH DEFINITION OF RECOVERY. THE PROPOSED DEFINITION DESCRIBES RECOVERY AS A PROCESS THROUGH WHICH AN INDIVIDUAL PURSUES BOTH REMISSION FROM AUD AND CESSATION OF HEAVY DRINKING. FINALLY I WANT TO END BY TALKING ABOUT THE CURRENT SITUATION WHICH IS GRAVE. ALCOHOL IS A COPING RESPONSE, HYPERKATIFEIA, DEATHS OF DESPAIR AND COVID-19. SOME OF YOU MAY WONDER WHAT HYPERKATIFEIA IS. IT'S JUST SIMPLY A WORD TO DESCRIBE THE NEGATIVE EMOTIONAL STATE. ALCOHOL RELATED DEATHS IN THE UNITED STATES HAVE DOUBLED FROM 1999 TO 2017. THE DEATH RATES WERE HIGHEST AMONG MEN AND MIDDLE AGED AND OLDER ADULTS, THE DEATH RATES INCREASED OVER TIME ACROSS ALL AGE GROUPS EXCEPT 16 TO 20 AND 75 AND OLDER. INCREASE IN DEATH RATE OVER TIME WAS GREATER IN WOMEN THAN MEN. THESE STATISTICS ALIGN WITH OTHER RECENT REPORTS THAT HAVE HIGH HIGHLIGHTED CHANGING TRENDS IN DRINKING PATTERNS AND INCREASED CONSEQUENCES OF ALCOHOL IN WOMEN AND THE AGING POPULATION. ALCOHOL PLAYS A PROMINENT ROLE IN THESE DEATHS OF DESPAIR, AS THEY'RE DESCRIBED BY CASE AND DEATON. 15% OF ALL DRUG OVERDOSES, 26% OF SUICIDES AND AS I MENTIONED 50% OF LIVER DISEASE DEATHS. DEATHS OF DESPAIR CONTRIBUTE TO THE DECREASING LIFE EXPECTANCY IN THE UNITED STATES OBSERVED SINCE 2014, WHICH IS ILLUSTRATED ON THE RIGHT-HAND SLIDE, AND THESE PATTERNS OF INCREASED MORTALITY HAVE ALSO BEEN OBSERVED ACROSS MANY NOW RACIAL/ETHNIC GROUPS AND AGE GROUPS. SO ONE OF THE BIGGES CONCERNS IS THAT THE CURRENT PANDEMIC IS ONLY GOING TO CONTRIBUTE TO THESE DEATHS OF DESPAIR AND EXACERBATE SOME OF THE PROBLEMS THAT DRIVE ALCOHOL USE DISORDER. SO THERE ARE FOUR AREAS IN WHICH THERE'S AN INTERACTION OF COVID-19 AND ALCOHOL USE DISORDER AND ALCOHOL PROBLEMS. THERE'S ISOLATION AND STRESS ASSOCIATED WITH THE PANDEMIC COULD LEAD TO INCREASED ALCOHOL MISUSE, PHYSICAL DISTANCING CAN LEAD TO SOCIAL ISOLATION OR LOSS OF SOCIAL SUPPORT, WHICH CAN LEAD TO STRESS OR PRECYST TAPE RELAPSE FOR THOSE IN RECOVERY. PHYSICAL DISTANCNG ALSO POSTS CHALLENGES FOR TREATMENT AND RECOVERY. TELEHEALTH AND VIRTUAL MEETINGS CAN BE HELPFUL OPTIONS FOR INDIVIDUALS SEEKING TREATMENT OR RECOVERY FROM ALCOHOL USE DISORDER. BIOLOGICAL AND BEHAVIORAL EFFECTS OF ALCOHOL MISUSE COULD ALSO EXACERBATE THE PANDEMIC. ALCOHOL PRODUCES BEHAVIORAL DISINHIBITION THAT MAY PROMOTE RISKY BEHAVIOR AND LESS COMPLIANCE WITH GUIDELINES TO REDUCE THE SPREAD OF THE VIRUS, AND ALCOHOL COMPROMISES IMMUNE FUNCTION, INCREASING THE RISK AND SEVERITY OF LUNG INFECTIONS AND THIS BIDIRECTIONAL RELATIONSHIP IS ILLUSTRATED IN THE DIAGRAM ON THE RIGHT WHERE SOCIAL ISOLATION, ALCOHOL MISUSE, BEHAVIORAL DISINHIBITION AND IMPAIRED IMMUNE FUNCTION CAN LEAD TO INCREASED RISK OF VIRAL INFECTION, WHICH LEADS TO SOCIAL ISOLATION AND STRESS WHICH LEAD TO ALCOHOL MISUSE. SURVEYS OF CONSUMERS IN THE U.S. AND ELSEWHERE SUGGEST THAT SOME PEOPLE ARE DRINKING MORE WHILE OTHERS ARE DRINKING LESS. ALCOHOL USE INCREASED AMONG COLLEGE STUDENTS IN MARCH, PARTICULARLY AMONG THOSE REPORTING HIGHER LEVELS OF STRESS AND ANXIETY. PEOPLE WHO SAID THEIR PSYCHOLOGICAL WELL-BEING WAS IMPACTED NEGATIVELY BY THE PANDEMIC ALSO REPORTED MORE DRINKING DAYS AND MORE DRINKS PER OCCASION. AN AUSTRALIAN SURVEY FOUND THAT 20% OF PEOPLE REPORTED DRINKING MORE DURING THE PANDEMIC AND HALF ENDORSED STRESS, ANXIETY, BOREDOM OR WORRY ABOUT COVID-19 AS REASONS FOR DRINKING MORE. SUCH FINDINGS ARE CONCERNING GIVEN THAT DRINKING TO COPE PLACES A PERSON ON A SLIPPERY SLOPE TO ALCOHOL USE DISORDER. IN ADDITION, INCREASES IN CONSUMPTION CAN INCREASE THE RISK OF INJURIES AT A TIME WHEN MANY HOSPITALS ARE INUNDATED WITH SICK PATIENTS. SO THIS IS ALL SUPERIMPOSED ON OUR HEURISTIC THREE-STAGE MODEL, ISOLATION AND STRESS RELATED TO THE COVID-19 PANDEMIC CAN EXACERBATE SOME OF THE STRESS AND NEGATIVE AFFECT THAT WE ALREADY EXPERIENCE WHEN WE MISUSE ALCOHOL. AND FINALLY, YOU CAN UNDERSTAND THAT ALL OF THESE FACTORS, GENETIC, EPIGENETIC, CHILDHOOD TRAUMA, CO-MORBIDITY, CURRENT PANDEMIC AND SOCIAL ISOLATION CAN PUT A LOAD ON OUR HOMEOSTATIC PROCESSES THAT WE CALL ALLOSTATIC LOAD TO SHIFT US INTO A VERY FRAGILE PHYSIOLOGIC STATE THAT MAKES US VULNERABLE FOR ALCOHOL USE DISORDER AND ALCOHOL MISUSE. FINALLY, I MUST ILLUSTRATE THAT NIAAA HAS A COMMITMENT TO SUPPORTING DIVERSE COMMUNITY -- DIVERSE -- SUPPORTING A DIVERSE RESEARCH COMMUNITY AND RESEARCH ON HEALTH DISPARITIES. HEALTH DISPARITIES HIGHLIGHTED BY THE COVID-19 PANDEMIC AND THE RECENT INSTANCES OF SOCIAL INJUSTICE AMONG AFRICAN AMERICANS ARE A CALL TO ACTION FOR NIH AND THE ENTIRE SCIENTIFIC COMMUNITY. NIAAA RECOGNIZES THAT DIVERSE RESEARCH TEAMS BROADEN THE SCOPE OF SCIENTIFIC INQUIRY, BRING CREATIVE SOLUTIONS TO BEAR ON COMPLEX SCIENTIFIC PROBLEMS, AND ENCOURAGE RESEARCH RELEVANT TO HEALTHCARE NEEDS OF UNDERSERVED POPULATIONS. TO ELIMINATE HEALTH DISPARITIES AND DIVERSIFY THE SCIENTIFIC WORKFORCE, NIAAA IS COMMITTED TO SIGNIFICANTLY INCREASING DIVERSITY AND FULLY EMBRACING INCLUSION IN THE SCIENTIFIC WORKFORCE, ELIMINATING DISPARITIES IN FUNDING AMONG GRANTEES FROM UNDERREPRESENTED GROUPS, EXPANDING HEALTH DISPARITIES RESEARCH, ENSURING THAT OUR RESEARCH AND OUTREACH BENEFITS UNDERSERVED COMMUNITIES. I JUST CAN'T EMPHASIZE ENOUGH THAT THE REAL WAY FOR SUCCESS IN RESEARCH IS THAT WE HAVE A DIVERSE COMMUNITY THAT WORKS IN RESEARCH THAT BENEFITS FROM RESEARCH AND THAT DOES RESEARCH. SO THIS IS OUR LINEUP FOR TODAY. I WILL BE INTRODUCING EACH OF THE SPEAKERS AT THE APPROPRIATE TIMES. I'M NOT GOING TO DWELL ON THIS OUTLINE BECAUSE YOU ALL HAVE IT AND WE WILL FOLLOW IT IN THE NEXT FEW MINUTES. I WANT TO GIVE A SPECIAL THANKS TO RACHEL HENDERSON FOR PREPARING ALL THESE SLIDES AND WORKING WITH ME ON THIS, BUT I WANT TO THANK ALL OF NIAAA FOR EVERYTHING THAT THEY DO, EVERYTHING THAT THEY'RE GOING TO BE DOING, IN OUR NEXT 50 YEARS. SO THANK YOU VERY MUCH. SO IT IS WITH GREAT PLEASURE THAT I INTRODUCE OUR FIRST SPEAKER OUR FIRST PRESENTER IS DR. KATHERINE KEYES, DIRECTOR OF THE PSYCHIATRIC AND EPIDEMIOLOGY TRAINING PROGRAM AT COLUMBIA UNIVERSITY'S SCHOOL OF PUBLIC HEALTH. HER RESEARCH FOCUSES ON PSYCHIATRIC AND SUBSTANCE USE EPIDEMIOLOGY ACROSS THE LIFESPAN, INCLUDING EARLY ORIGINS OF CHILD AND ADULT HEALTH AND CROSS-GENERATIONAL COHORT EFFECTS ON ALCOHOL AND SUBSTANCE USE, MENTAL HEALTH, AND INJURY OUTCOMES, INCLUDING SUICIDE AND OVERDOSE. THE TITLE OF HER PRESENTATION TODAY IS: AGE, PERIOD AND COHORT EFFECTS IN ALCOHOL USE IN THE 20TH AND 21ST CENTURIES, IMPLICATIONS FOR DECADES TO COME. I'M NOW -- SO IT'S ALL YOURS, KATHERINE. >> GOOD MORNING, AND THANK YOU FOR THIS VERY SINCERE PRIVILEGE OF PRESENTING ON THIS REALLY IMPORTANT OCCASION. NIAAA HAS BEEN TRULY INSTRUMENTAL TO MY CAREER TRULY SINCE THE BEGINNING. NOT ONLY DID THEY FUND MY MENTORS THROUGHOUT MY DOCTORAL PROGRAM BUT I WAS FORTUNATE THEY SUPPORTED ONE OF MY FIRST NIH GRANTS, THE K01, THAT REALLY SUPPLEMENTED MY CAREER AS AN ALCOHOL EPIDEMIOLOGIST. I'VE GONE ON TO BE FORTUNATE TO RECEIVE MORE FUNDING FOR MY WORK FROM NIAAA THANKS TO SUPPORTIVE LEADERSHIP AND STAFF. AND IT'S THIS NIAAA FUNDED WORK AND SUPPORTED WORK THAT I'LL BE DISCUSSING TODAY. NOW OVER THE NEXT SEVERAL DAYS, AN IMPRESSIVE ARRAY OF INVESTIGATORS HAVE BEEN ASSEMBLED FOR THIS TWO-DAY SYMPOSIUM AND THEY'LL TAKE EVERYONE DEEP INTO THE WEEDS OF ALCOHOL SCIENCE. AND WHAT I'M GOING TO DO IS THE OPPOSITE. I'M GOING TO PROVIDE THE 30,000-FOOT VIEW OF ALCOHOL SURVEILLANCE HISTORY, POPULATION HEALTH DISTRIBUTIONS AND WHAT TO EXPECT IN THE COMING DECADES REGARDING THE PREVALENCE OF ALCOHOL USE AND ALCOHOL USE DISORDERS THROUGH THE LENS OF AGE, PERIOD AND COHORT EFFECTS. SO LET'S BEGIN BY JUST RECOGNIZING HOW MUCH VARIATION THERE IS AT THE POPULATION LEVEL IN ALCOHOL CONSUMPTION OVER TIME. ONE WAY TO VISUALIZE THIS VARIATION IS THROUGH TRENDS PER CAPITA ETHANOL CONSUMPTION IN THE UNITED STATES THROUGH THIS GRAPH PRODUCED BY NIAAA. WE CAN SEE CLEARLY THAT ALCOHOL CONSUMPTION EBBS AND FLOWS WITH PEAK AND VALLEYS ACROSS TIME, BASED ON A VARIETY OF DIFFERENT ISSUES SUCH AS ALCOHOL POLICY, FOR EXAMPLE, WE SEE THE TIME OF PROHIBITION, WE SEE THE TIME PERIOD IN WHICH THE MINIMUM LEGAL DRINKING AGE WAS CHANGING, AND WE ALSO SEE VARIATION THAT COINCIDES WITH NATIONAL AND GLOBAL EVENTS SUCH AS WARS, RECESSIONS AND ECONOMIC STIMULUS, AS WELL AS A WHOLE HOST OF OTHER FACTORS PERTAINING TO NORMS AROUND ALCOHOL CONSUMPTION THAT PROMOTE OR DISCOURAGE HEAVY CONSUMPTION. AND WE CAN ALSO SEE THAT DESPITE MAJOR DECLINES IN CONSUMPTION THROUGHOUT THE 1980s AND 1990s, REALLY OVER THE LAST 10 TO 20 YEARS, THERE HAVE BEEN CONSISTENT INCREASES IN PER CAPITA ALCOHOL CONSUMPTION IN THE UNITED STATES OTHER THAN THIS RELATIVELY SMALL DIP DURING THE 2008 ECONOMIC RECESSION. AND MY RESEARCH PROGRAM AND RESEARCH CAREER IS FOCUSED ON ASKING THE QUESTION OF WHY. WHY DOES ALCOHOL CONSUMPTION INCREASE AND DECREASE AND HOW DO WE KNOW THAT? AND IT BEGINS BY RECOGNIZING THAT THESE TIME TRENDS THAT WE CAN SEE IN ALCOHOL CONSUMPTION ARE REALLY THE PRODUCT OF THREE INTERSECTING PHENOMENA: AGE, PERIOD, AND COHORT EFFECTS. AGE EFFECTS TYPICALLY REPRESENT VARIATION ASSOCIATED WITH AGING. WHY ALCOHOL CONSUMPTION IS MORE COMMON AT SOME AGES THAN OTHERS. IT'S PROUT ABOUT BY PHYSIOLOGICAL CHANGES, THE ACCUMULATION OF SOCIAL EXPERIENCE, AND ROLE OR STATUS CHANGES. FOR EXAMPLE, WE KNOW FROM DECADES OF ALCOHOL EPIDEMIOLOGY, INCLUDING THESE DATA FROM THE NISART AND OTHER STUDIES THAT RISK FOR ALCOHOL USE DISORDER ONSET PEAKS IN LATE ADOLESCENCE AND EARLY ADULTHOOD, AND THAT INCIDENCE REMAINS ELEVATED THROUGHOUT THE TRANSITION TO ADULTHOOD WHERE IT THEN BEGINS TO DECLINE THEREAFTER. HOWEVER, THESE AGE EFFECTS INTERSECT WITH OTHER NATIONAL, GLOBAL EVENTS THAT ARE OCCURRING IN THE BROADER POPULATION. THESE ARE SOMETIMES REFERRED TO AS PERIOD EFFECTS. PERIOD EFFECTS ARE THINGS THAT REPRESENT VARIATION OVER TIME PERIODS THAT AFFECT ALL AGE GROUPS SIMULTANEOUSLY. THEY OFTEN RESULT FROM SHIFTS IN SOCIAL, CULTURAL, ECONOMIC OR PHYSICAL ENVIRONMENTS. ONE OF THE MOST OBVIOUS EXAMPLES IN THE ALCOHOL LITERATURE IS U.S. PROHIBITION OF ALCOHOL FROM 1920 TO 1933. WHICH RESTRICTED ACCESS TO ALCOHOL ACROSS ALL AGE GROUPS. AND WHILE ALCOHOL WAS STILL ACCESSED DURING PROHIBITION, AVAILABLE EVIDENCE INDICATES THERE WAS A DECLINE IN BOTH ACUTE AND CHRONIC ALCOHOL-RELATED MORBIDITY ACROSS THE ENTIRE POPULATION DURING THE TIME OF PROHIBITION. SOMETIMES WE'RE REALLY CONCEPTUALLY INTERESTED IN THESE PERIOD EFFECTS AND HOW THEY MIGHT INTERSECT ACROSS AGE AND BIRTH COHORT, AS IN THE EXAMPLE OF U.S. PROHIBITION. AND SOMETIMES THEY CAN BE NUISANCE FACTORS THAT WE WANT TO CONTROL OUT OF TIME TREND ANALYSIS. SO THINGS LIKE CHANGES IN DIAGNOSTIC CRITERIA THAT WOULD APPLY TO ALL INDIVIDUALS IN THE POPULATION, OR THE INTRODUCTION OF SOMETHING LIKE BETTER SCREENING, SO WE'RE ABLE TO DETECT MORE PEOPLE WHO HAVE ALCOHOL USE DISORDERS. OR METHODOLOGICAL CHANGES IN SURVEY ADMINISTRATION. ALL OF THOSE MAY MANIFEST AS PERIOD EFFECTS AT A POPULATION LEVEL. FINALLY, THERE'S BIRTH COHORT EFFECTS THAT I'LL SPEND SOME TIME DISCUSSING THE RESULTS FROM ALCOHOL EPIDEMIOLOGY TODAY. BIRTH COHORT EFFECTS, SHOWN HERE AS THE COHORT THAT CAME OF AGE IN THEIR ADOLESCENCE AND YOUNG ADULTHOOD IN THE LATE 1960s, WHEN THERE WAS MORE PERMISSIVE ATTITUDES TOWARDS SUBSTANCE USE INCLUDING ALCOHOL USE, AND THE IDEA IS THAT SOME BIRTH COHORTS HAVE DIFFERENT LEVELS OF HEALTH-RELATED CONDITIONS THAT THEY CARRY WITH THEM THROUGH THE LIFE COURSE. SO THESE COHORT EFFECTS ARE ASSOCIATED WITH CHANGES ACROSS GROUPS OF INDIVIDUALS WHO ARE BORN AROUND THE SAME YEAR, AND THEY REFLECT THE EFFECT OF HAVING FORMATIVE EXPERIENCES AT A PARTICULA AGE IN A PARTICULAR TIME PERIOD. FOR EXAMPLE, IN ALCOHOL EPIDEMIOLOGY, WE KNOW THE EXPOSURE TO INCREASED ACCESS TO ALCOHOL EARLIER IN THE LIFE COURSE, FOR EXAMPLE, THROUGH EARLIER MINIMUM LEGAL DRINKING AGE, IS ASSOCIATED WITH DIFFERENCES IN DRINKING PATTERNS THAT REMAIN THROUGHOUT THE ENTIRETY OF THE LIFE COURSE. SO SOME COHORTS, DEPENDING ON WHEN THEY'RE EXPOSED TO ALCOHOL, DEPENDING ON THE NORMS AND OTHER ALCOHOL POLICIES THAT ARE PRESENT WHEN EACH COHORT MOVES THROUGH ADOLESCENCE AND YOUNG ADULTHOOD DURING THESE HEIGHTENED PERIODS OF RISK FOR ALCOHOL USE DISORDERS, CARRY WITH THEM AN IMPRINT OF THAT FORMATIVE EXPERIENCE AS THEY AGE THE LIFE COURSE. AND IT IS WITHIN THESE THREE SOURCES OF TIME-RELATED VARIATION: AGE, PERIOD, AND COHORT EFFECTS, THAT WE NEED TO PARSE THESE OVERALL TRENDS OVER TIME AND WE ACTUALLY WANT TO MAKE SENSE OF OR UNDERSTAND THE ETIOLOGY OF OR DESIGN INTERVENTION AND PREVENTION PROGRAMS TO AMELIORATE PROBLEMATIC ALCOHOL PATTERNS OVER TIME. AND REALLY, DECADES AND CENTURIES OF EPIDEMIOLOGICAL WORK HAS DEMONSTRATED REALLY THE PROFOUND IMPORTANCE OF IDENTIFYING THESE COHORT EFFECTS. COHORT EFFECTS IN PARTICULAR HAVE PROVEN TO BE CRITICALLY IMPORTANT FOR UNDERSTANDING HEALTH AND MORTALITY ACROSS THE WORLD. AND TO BEGIN TO ILLUSTRATE THE IMPORTANCE OF HEALTH COHORTS FOR BIRTH AND DISEASE, I'LL JUST GO THROUGH ONE OF THE EARLY YIS AND I THINK ENGAGING EXAMPLES OF BIRTH COHORT EFFECTS AND MORTALITY, WHICH IS MORTALITY RATES IN ENGLAND AND WALES FROM 1845 TO 1925. EACH ROW REPRESENTS A YEAR OF -- AN AGE AT WHICH SOMEONE DIES. SO WE HAVE PEOPLE WHO DIED IN INFANCY, PEOPLE WHO DIED AT AGE 10, PEOPLE WHO DIED AT AGE 20, 30, 40, ET CETERA. EACH COLUMN REPRESENTS THE DECADE IN WHICH THEY DIED, SO THESE ARE PEOPLE WHO DIED IN 1845, 1855, 1865, 1875. EACH CELL IN THIS TABLE IS THE RELATIVE MORTALITY RATE COMPARED TO SOMEONE OF THE SAME AGE WHO DIED IN 1845. SO THESE ARE ALL THE REFERENCE GROUPS. EVERYONE STARTS AT 100, AND THEN EACH CELL REPRESENTS THE RELATIVE MORTALITY RATE COMPARED TO THAT AGE IN 1845. AND YOU CAN SEE OVERALL THAT MORTALITY IS DECLINING. IF YOU LOOK AT THESE RELATIVE MORTALITY RATES IN 19 FEN 1915 AND 1925, YOU'LL SEE THE MORTALITY RATE IS ALMOST HALVED COMPARED TO THAT IN 1845. BUT WHAT KERMACK AND COLLEAGUES DID IN THIS PAPER IS THEY STARTED TO DRAW LINES AROUND THOSE RELATIVE MORTALITY RATES THAT WERE SIMILAR. SO SHOWN IN THIS KIND OF BAND HERE ARE ALL THE MORTALITY RATES THAT ARE IN THE 80s. SHOWN HERE IS THE 70s AND 60s. SHOWN HERE IS THE 50s. SO THIS REPRESENTS HALF THE MORTALITY RATE OF THAT SAME AGE AT THE EARLIER TIME PERIOD. THEN IT'S DOWN TO 40 AND 30, ET CETERA. WHAT'S REMARKABLE ABOUT THIS IS THAT THOSE DIAGONALS REPRESENT INDIVIDUALS WHO ARE FROM THE SAME BIRTH COHORT. BECAUSE INDIVIDUALS WHO DIED IN INFANCY IN 1855, FOR EXAMPLE, WERE BORN IN THE SAME YEAR AS PEOPLE WHO DIED AT AGE 10 IN 1865, AGE 20 IN 1875, AGE 30 IN 1885, ET CETERA. SO THE RELATIVE MORTALITY RATE FOLLOWED A BIRTH COHORT TRAJECTORY EVEN THOUGH IT WAS GETTING BETDER ACROSS THE ENTIRE POPULATION, IT WAS GETTING BETTER FOR EACH COHORT AS THEY MOVED THROUGH THE LIFE COURSE. AND THIS FINDING FROM KERMACK HAS BEEN REPLICATED IN MANY DIFFERENT COUNTRIES ACROSS MANY DIFFERENT TIME PERIOD THAT EACH HAS AN IMPRINT, THESE IDEAS OF COHORT-RELATED PHENOTYPES, THAT YOU CARRY IT WITH YOU ALONGSIDE OTHER PEOPLE WHO ARE BORN IN OR AROUND THE SAME TIME, AND THEY REALLY SHAPE A LOT OF HEALTH-RELATED BEHAVIORS, INCLUDING THINGS LIKE SMOKING, ALCOHOL CONSUMPTION, AND OTHER DRUG USE. SO THESE COHORT EFFECTS HAVE REALLY FORMED AN IMPORTANT FOUNDATION OF HOW WE UNDERSTAND MORTALITY RATES ACROSS THE WORLD AND AGAIN THEY'VE BEEN REPEATED TIME AND TIME AGAIN. AND IF WE FAST FORWARD TO THE CURRENT GENERATION IN THE U.S., AGE, PERIOD AND COHORT EFFECTS REMAIN CENTRAL SOURCES OF MORTALITY VARIATION. AS CASE AND DEATON DEMONSTRATED IN THEIR 2015 PAPER, NOT ONLY IS THE U.S. LAGGING BEHIND SIMILARLY POSITIONED NATIONS IN LIFE EXPECTANCY, BUT THE CAUSES OF DEATH THAT ARE PARTICULARLY INCREASING IN THE U.S. ARE THOSE ASSOCIATED WITH PSYCHIATRIC DISORDERS AND SUBSTANCE USE, INCLUDING DRUG POISONING, SUICIDE, AND CHRONIC LIVER DISEASE, ESPECIALLY FOR THOSE IN MID LIFE. SO WE KNOW THAT MORTALITY RATES STRUCTURE AROUND BIRTH COHORTS AND THAT ALCOHOL IS A MAJOR DRIVER OF MORBIDITY AND MORTALITY, AND THAT ALCOHOL USE HAS BEEN INCREASING IN THE UNITED STATES IN RECENT YEARS. WHICH BEGS THE QUESTION OF HOW ALCOHOL USE OUTCOMES THEMSELVES ARE PATTERNING ACROSS BIRTH COHORTS, AND WHAT WE CAN LEARN ABOUT THE SOCIAL AND ENVIRONMENTAL DRIVERS OF ALCOHOL USE FROM EXAMINING AGE, PERIOD AND COHORT PARAMETERS. SO STATISTICALLY, SEPARATING AGE, PERIOD AND COHORT EFFECTS PRESENTS ANALYTICAL CHALLENGES GIVEN THAT THEY ARE LINEARLY RELATED. COHORT IS FULLY A FUNCTION OF PERIOD AND AGE. IF I KNOW SOMEONE'S AGE IN A PARTICULAR YEAR, I CAN DIRECTLY CALCULATE WHAT THEIR BIRTH COHORT IS. AND PART OF MY RESEARCH PORTFOLIO IS DEVELOPING, ADVANCING AND IMPLEMENTING ESTIMATES IN A WIDE VARIETY OF DATA STRUCTURES. AND WHILE I WON'T GET INTO THE SPECIFICS OF THESE ESTIMATION AND ANALYTIC PLANS IN TODAY'S TALK, SUFFICE TO SAY EACH METHOD THAT EITHER I OR OTHERS HAVE DEVELOPED FOR ESTIMATING AGE, PERIOD AND COHORT EFFECTS HAS A SET OF ASSUMPTIONS FOR IDENTIFICATION. AND THOSE ASSUMPTIONS CAN MAKE THE RESULTS SENSITIVE TO MODELING STRATEGIES. SO THAT'S BEEN A MAJOR TOPIC IN THE FIELD. BUT KIND OF PUTTING THAT ASIDE, I'LL GIVE YOU SOME RESULTS ACROSS DIFFERENT DATASETS USING DIFFERENT ANALYTICAL TECHNIQUES THAT ARE CONVERGING ON SOME REPLICABLE FINDINGS. SO WHEN WE CONDUCT THESE ANALYSES OF AGE, PERIOD AND COHORT EFFECTS AND ALCOHOL-RELATED OUTCOMES, ACROSS A WIDE VARIETY OF DATA SOURCES, WE DO FIND THAT BIRTH COHORT EFFECTS, WHEN WE SEPARATE OUT THE VARIANCE FOR COHORTS FROM PERIOD AND AGE, ARE EVIDENT, INDICATING THAT PARTICULAR BIRTH COHORTS HAVE PARTICULAR MARKERS OF HEAVY DRINKING THAT THEY CARRY WITH THEM THROUGHOUT THE LIFE COURSE. FOR EXAMPLE, THESE ARE DATA FROM THE NATIONAL HOUSEHOLD SURVEY ON DRUG USE AND HEALTH FROM 1985 THROUGH 2009. AND THEY SHOW BIRTH COHORT EFFECTS FOR MOST COHORTS BORN IN THE 20TH CENTURY. EACH OF THE BARS HERE REPRESENT THE AVERAGE AMOUNT OF BINGE DRINKING FOR EACH COHORT AVERAGED OVER THEIR LIFE COURSE. SO EACH OF THESE VALUES IS THE AVERAGE AMOUNT OF BINGE DRINKING AFTER YOU SEPARATE OUT VARIATION DUE TO AGE, VARIATION DUE TO PERIOD, WHAT BIRTH COHORTS ARE JUST HEAVY DRINKING FROM ADOLESCENCE THROUGH TO OLDER AGE. AND IT'S CLEAR SOME OF THESE COHORTS ARE HEAVY DRINKING COHORTS. THESE COHORTS IN PARTICULAR RIGHT HERE FOR MEN AND PARTICULARLY KIND AFTER WORLD WAR II, THE COHORTS BORN AFTER WORLD WAR II AND SORT OF THAT BINGE DRINKING ACROSS THE LIFE COURSE INCREASED RISK PEAKS IN THESE LATE 1970s/EARLY 1980s COHORTS. FOR WOMEN, YOU SEE A SIMILAR PHENOMENON, ALTHOUGH THE PEAK OF THEIR BINGE DRINKING IS SLIGHTLY YOUNG YOUNGER BUT THESE COHORTS THROUGH THE LATE 1970s AND EARLY 1980s COHORTS ARE HEAVY DRINKING COHORTS, MEANING WHATEVER THE AGE, THEY'RE DRINKING MORE THAN SIMILAR COHORTS WERE DRINKING WHEN THEY WERE THAT AGE. AND YOU CAN SEE THAT FROM THESE NEGATIVE COHORT EFFECTS DOWN HERE. THE SAME RANGE OF COHORT EFFECTS HAS BEEN INDEPENDENTLY REPLICATED IN OTHER STUDIES, SUCH AS THE NATIONAL ALCOHOL SURVEYS. SO SHOWN HERE ARE DATA FROM THE NATIONAL ALCOHOL SURVEYS COVERING RELATIVELY SIMILAR TIME PERIODS, 1979 TO 2010, WITH NOW EACH LINE REPRESENTING THE COHORT EFFECT FOR AND SEPARATED BY BEVERIDGE TYPE TOO. SO FOR BEER, SPIRITS AND WINE, ON THE LEFT-HAND SIDE IS FOR MEN AND THE RIGHT-HAND SIDE IS FOR WOMEN. ACROSS DIFFERENT BEVERAGE TYPES AND ACROSS MALE AND FEMALE, WE DO SEE THESE POST WORLD WAR II COHORTS HAVE AN INCREASED COHORT EFFECT, SO AGAIN, EACH OF THESE DOTS REPRESENTS THE AVERAGE OVER THE LIFE COURSE FOR EACH OF THESE COHORTS AFTER VARIANTS DUE TO AGE AND PERIOD HAVE BEEN EXTRACTED, WITH THEET LATE 1970s, EARLY 1980s COHORTS HAVING A PEAK OF THAT COHORT EFFECT IN TERMS OF THEIR LEVEL OF DRINKING COMPARED TO OTHER COHORTS WHO WERE AT THAT AGE IN OTHER GENERATIONS. AND YOU CAN SEE IT REALLY ACROSS DIFFERENT BEVERAGE TYPES AND ACROSS GENDER AS WELL. WHILE THE ANALYSES THAT I'VE JUST SHOWED YOU PRESENT DATA STRATIFIED BY SEX, TRENDS OVER TIME IN SEX DIFFERENCES IN DRINKING BY COMPARING THE ACTUAL RATIO OF MALE TO FEMALE DRINKERS, IT'S ALSO IMPORTANT BECAUSE NOT ONLY IS IT VARYING OVER TIME, BUT IT PROVIDES A LENS INTO HOW THESE COHORT EFFECTS OPERATE AND A FRAMEWORK TO THINK ABOUT WHAT WE EXPECT IN ALCOHOL SURVEILLANCE IN THE COMING DECADE. SO THERE HAVE BEEN SEVERAL REVIEWS AND META ANALYSES OF GENDER DIFFERENCES IN ALCOHOL USE BOTH IN THE U.S. AND WORLDWIDE, AND THIS INCLUDES A REVIEW THAT I CONDUCTED IN 2011, WITH MY COLLEAGUES, WHERE WE FOUND SUBSTANTIAL EVIDENCE REVIEWING DOZENS OF STUDIES THAT THERE ARE COHORT BY GENDER INTERACTIONS IN ALCOHOL USE THAT REALLY BEGAN IN THAT POST-WORLD WAR II PERIOD, AND COVERED ALL OF THE ALCOHOL SURVEILLANCE THAT WE HAD DONE UP UNTIL THE TIME, WHICH AGAIN IS ABOUT, YOU KNOW, COMING ON A DECADE AGO. SO I'M GOING TO UPDATE YOU ON THE LAST DECADE IN A MINUTE. BUT JUST FOCUSING ON THIS, WE FOUND THAT IF YOU LOOK AFTER WORLD WAR II, THERE'S STRONG EVIDENCE FOR A GENDER BY COHORT INTERACTION WITH WOMEN IN YOUNGER COHORTS ESCALATING DRINKING FASTER THAN MEN IN YOUNGER COHORTS. WE'VE SINCE DONE MORE ANALYSES AND WITH MY COLLEAGUES IN AUSTRALIA, WE CONDUCTED AN UPDATED META REGRESSION OF ALL OF THE STUDIES THAT HAVE ESTIMATED COHORT BY GENDER INTERACTIONS IN ALCOHOL USE, AND IN THIS KIND OF BROAD CATEGORY THAT WE CALL PROBLEMATIC ALCOHOL USE, WHICH THE DEFINITION VARIED ACROSS STUDIES BUT KIND OF PUTTING THEM ALL TOGETHER IN STUDIES THAT WERE ESTIMATING PROBLEMATIC ALCOHOL USE, WHAT WE FOUND IN THIS META REGRESSION IS THAT IF YOU LOOK AT ALL THE STUDIES THAT EXAMINED COHORTS REALLY ACROSS THE 20TH CENTURY, THE GENDER RATIO OF OVERREPRESENTING MEN IN PROBLEM ALCOHOL-RELATED -- PROBLEM ALCOHOL USE WAS BETWEEN 2 AND 3 TO 1. SO TWO AND THREE TIMES MORE PROBLEMATIC ALCOHOL USE IN MEN COMPARED TO WOMEN. BUT SURE ENOUGH, WHEN YOU START LOOKING AT THIS POST-WORLD WAR II PERIOD AND ESPECIALLY IN RECENT TIMES, STARTING WITH THAT LATE 1970s/EARLY 1980s COHORTS, THE GENDER RATIOS BEGIN TO DECLINE. AND BY THE MOST RECENT BIRTH COHORT THAT WE HAD DATA TO EXAMINE, WE'RE MOVING TOWARDS TOTAL CONVERGENCE BETWEEN MEN AND WOMEN IN PROBLEMATIC ALCOHOL USE. SO KIND OF TO SUMMARIZE, THE EVIDENCE INDICATES THAT THROUGH MUCH OF THE COURSE OF THE LAST HALF OF THE 20TH CENTURY AND NOW MOVING IN TO THE 21ST CENTURY, COHORTS IN THE U.S. SHOWING HIGH LEVELS OF USE PARTICULARLY FOR THOSE BORN BETWEEN THE LATE 1970s AND EARLY 1980s, AND THAT THESE COHORT EFFECTS ARE GENERATING CONVERGENCES IN ALCOHOL USE BY SEX. BUT WHAT ABOUT THE LAST 10 YEARS? WHAT I'VE SHOWN YOU SO FAR USUALLY ENDS AROUND 2010, 2011 AND WE'VE HAD A DECADE MORE OF DATA TO SEE WHAT'S GOING ON MORE RECENTLY. WELL, WE KNOW THAT AMONG ADOLESCENTS, ALCOHOL USE AND BINGE DRINKING IS CONTINUING TO CLIMB TO HISTORIC LOWS. SO SHOWN HERE ARE DATA FROM MONITORING THE FUTURE, A NATIONALLY REPRESENTATIVE STUDY THAT'S CONDUCTED EVERY YEAR, WITH THE PREVALENCE OF BINGE DRINKING AMONG HIGH SCHOOL SENIORS ON THE LEFT, AND THE PREVALENCE OF DAILY DRINKING IN THE LAST 30 DAYS ON THE RIGHT. AND WE CAN SEE THAT OVERALL, THROUGHOUT MUCH OF THE LAST 45 YEARS, BINGE DRINKING AND DAILY DRINKING ARE ON A PRETTY STEEP DECLINE. SHOWN HERE IS MALES, SHOWN HERE IS GIRLS. BUT THIS DECLINE HAS BEEN FASTER FOR BOYS COMPARED TO GIRLS SUCH THAT THERE IS A COHORT BY GENDER INTERACTION, THERE IS A MUCH BIGGER DIFFERENCE IN 12TH GRADE COHORTS BETWEEN BOYS AND GIRLS IN THE LATE 1970s, EARLY 1980s, THAN THERE IS NOW, AND WE SEEM THE SAME PHENOMENON FOR DAILY DRINKING AS WELL. SO ADOLESCENTS, GOOD STORY, THEY'RE DECLINING DRINKING, WE'RE AT HISTORIC LOWS FOR BOTH BOYS AND GIRLS. AND THE GENDER DIFFERENCES ARE CONVERGENT BECAUSE MEN ARE DECREASING -- MEN AND BOYS ARE DECREASING FASTER THAN GIRLS. BUT AMONG ADULTS, A DIFFERENT STORY IS EMERGING. THESE ARE DATA SHOWN HERE ON PAST-YEAR BINGE DRINKING PREVALENCE AMONG ALCOHOL USERS, META ANALYZED ACROSS SIX NATIONAL STUDIES THAT TRACK ALCOHOL USE. SHOWING THAT ALCOHOL USE AMONG ADULTS IS INCREASING. THAT'S WHAT WE SEE IN THIS BLACK LINE, INCREASING ALCOHOL CONSUMPTION FROM 2000 TO 2015. BUT THE INCREASES IN ALCOHOL CONSUMPTION ARE ALMOST EXCLUSIVELY DRIVEN BY WOMEN. ADULT WOMEN, INCREASING THEIR DRINKING AT A MUCH FASTER RATE THAN MEN. SO AGAIN, IN 2000, WE SAW A GREATER GENDER GAP THAN WE SEE IN 2015, BUT UNLIKE THE ADOLESCENTS, THE GENDER GAP IS NOT CONVERGING BECAUSE BOYS ARE DECLINING FASTER. THE GENDER GAP IS CONVERGING BECAUSE WOMEN ARE INCREASING FASTER. THESE TRENDS, THE DECLINING PREVALENCE OF ALCOHOL USE AMONG ADOLESCENTS AND THE INCREASING PREVALENCE OF ALCOHOL USE AMONG ADULTS ARE ACTUALLY INTERCONNECTED THROUGH THE VERY SAME COHORT EFFECTS THAT WE'VE BEEN TALKING ABOUT THROUGHOUT THIS PRESENTATION. AND WE ARE REALLY LUCKY IN MONITORING THE FUTURE. IT AFFORDS US THE OPPORTUNITY TO EXAMINE THE ALCOHOL CONSUMPTION EXPERIENCE OF EACH BIRTH COHORT AS THEY LONGITUDINALLY PROGRESS THROUGH THE LIFE COURSE, BECAUSE WE REPEATEDLY FOLLOW EACH 12TH GRADE COHORT LONGITUDALLY THROUGHOUT THEIR ENTIRE ADULTHOOD. THAT ALLOWS US TO CONNECT WHAT'S GOING ON WITH THE 12TH GRADE COHORTS TO THEIR EXPERIENCE DURING THEIR TRANSITION TO ADULTHOOD. THIS CONNECTED PICTURE IS REALLY ILLUMINATING. SO SHOWN HERE ON THE X AXIS IS THE YEERL THAT MONITORING THE FUTURE RESPONDENTS WERE 18 YEARS OLD. SO SOME WERE 18 YEARS OLD IN 1976, SOME WERE 18 YEARS OLD IN 2003. AND GRAPHED HERE IS THE PREVALENCE OF BINGE DRINKING FOR EACH OF THOSE COHORTS. BOYS IN BLACK AND GIRLS IN GREY. AND WE CAN SEE OVERALL JUST LIKE WE SEE IN THE DEDESCRIPTIVE GRAPH THAT BINGE DRINK SOMETHING DECLINING FOR THESE COHORTS, ESPECIALLY WHEN WE MOVED THROUGH THE 80s AND MINIMUM LEGAL DRINKING AGE CHANGED, YOU CAN SEE PRETTY STRONG DECLINE IN BINGE DRINKING FOR BOTH BOYS AND GIRLS. THESE ARE THE SAME COHORTS, THE SAME PEOPLE, WHEN THEY'RE 30 YEARS OLD, AND AGAIN, GRAPHED HERE ON THE X AXIS IS THE YEAR THAT THE RESPONDENTS WERE 18 YEARS OLD. SO FOR EXAMPLE, THOSE WHO WERE 18 YEARS OLD IN 2003, THEY'RE NOW 30 YEARS OLD IN 2015. AND WHAT WE SEE HERE IS ACTUALLY AN INCREASING SLOPE FOR BOTH BOYS AND GIRLS, ESPECIALLY DURING THAT 19 -- THE COHORT -- THE COHORTS THAT WERE 18 DURING THE 1980s. SO YOU CAN THINK OF IT LIKE A TEETER-TOTTER, RIGHT? AS THE PREVALENCE OF BINGE DRINKING AT AGE 18 DECLINES, THOSE SAME COHORTS ARE ACCELERATING THEIR DRINKING MORE DURING THE TRANSITION TO ADULTHOOD. SUCH THAT WE SEE AN INCREASING PREVALENCE IN ALCOHOL USE AMONG ADULTS IN THE UNITED STATES. AND THEY ARE THE VERY SAME COHORTS THAT HAD THE DECREASING PREVALENCE AT AGE 18. AND CERTAINLY WHAT THIS INDICATES IS THAT ALCOHOL PREVENTION DOESN'T STOP IN ADOLESCENTS, RIGHT? WE NEED TO SHIFT SOME OF OUR FOCUS OR NOT EVEN SHIFT BUT ALIGN SOME OF OUR FOCUS ON THE EXPERIENCES OF ADULTS IN THE IN THE UNITED STATES BECAUSE THOSE ARE THE PEOPLE THAT ARE ESCALATING ALCOHOL CONSUMPTION, ESPECIALLY WI. WOMEN. SO GIVEN THAT WE HAVE THIS MID LIFE INCREASE IN ALCOHOL USE, PART OF MY RESEARCH PORTFOLIO IN THE PAST SEVERAL YEARS HAS BEEN TRYING TO INTERROGATE WHY AND AMONG WHOM AND LIKE WHO AMONG THESE FEMALE COHORTS ARE AT THE HIGHEST RISK FOR THIS INCREASE IN CONSUMPTION. SO AS JUST ONE EXAMPLE, THERE'S BEEN SUBSTANTIAL REPORTING AND ARTICLES AND MAGAZINES THAT INCREASES IN ALCOHOL CONSUMPTION AMONG ADULT WOMEN IS BEING DRIVEN BY SO-CALLED MOMMY DRINKING, THAT ALCOHOL USE AMONG WOMEN WHO ARE PARENTING YOUNG CHILDREN IS BECOMING FA FASHIONABLE AND SOCIALLY ACCEPTABLE. SO WE WANTED TO INTERROGATE THAT. IS THERE ANY EVIDENCE FOR AN INCREASE IN ALCOHOL CONSUMPTION THAT'S BEING PARTICULARLY DRIVEN BY WOMEN WHO ARE PARENTING YOUNG CHILDREN? SO WE USE DATA FROM THE NATIONAL HEALTH INTERVIEW SURVEY, AND WE STRATIFY BY THESE THREE DIFFERENT TIME PERIODS IN WHICH WOMEN WERE MOST LIKELY TO BE LIVING WITH YOUNG CHILDREN, 18 TO 29, 30 TO 44, 45 TO 55. AND WE EXTRACTED THE PEOPLE WHO WERE LIVING WITH SOMEONE IN THEIR HOME UNDER THE AGE OF 18. AND WE DIVIDED MEN AND WOMEN FROM 2006 TO 2018 BASED ON WHETHER THEY WERE LIVING IN A% HOME WITH SOMEONE UNDER 18 OR NOT. AND WHAT WE SAW WAS THAT THERE WAS VERY LITTLE EVIDENCE FOR THIS MOMMY DRINKING PHENOMENON. THIS SOLID RED LINE HERE IS WOMEN WITH CHILDREN AND THE TRENDS IN THEIR BINGE DRINKING OVER TIME. WOMEN WITH CHILDREN WERE AT THE LOWEST RISK FOR BINGE DRINKING ACROSS THESE DIFFERENT GROUPS THAT WE EXAMINED, AND THERE WAS A SLIGHT INCREASE AMONG WOMEN WITH CHILDREN AGED 30 TO 44, BUT NOT AS MUCH AS THIS DOTTED RED LINE, WHICH IS WOMEN WITHOUT CHILDREN. AND BOTH WOMEN WITH AND WITHOUT CHILDREN ARE NOT DRINKING AS MUCH AS MEN, WHO SIMILARLY TO ALL OTHER NATIONAL SURVEYS ARE DECLINING ALCOHOL CONSUMPTION, ESPECIALLY DURING THIS TRANSITION TO ADULTHOOD PERIOD, BUT ARE STILL DRINKING MORE THAN WOMEN. THE ONE EXCEPTION IS THIS CROSSOVER THAT'S OCCURRED WHERE NOW BETWEEN THE AGE OF 18 AND 29, WOMEN WITHOUT CHILDREN ARE CONSUMING ALCOHOL AT THE SAME FREQUENCY AS MEN WITH CHILDREN. SO IF MOMMY DRINKING IS NOT DRIVING THE INCREASES IN ALCOHOL CONSUMPTION AMONG ADULT WOMEN, WHAT ARE OTHER SOURCES OF VARIATION THAT WE CAN LK AT IN CAN LOOK AT TO IDENTIFY WHICH WOMEN ARE AT THE HIGHEST RISK. ONE WE WERE REALLY CURIOUS ABOUT WAS AXE EASE OF INCOME, EDUCATION AND SOCIOECONOMIC STATUS. HERE A REALLY INTERESTING PICTURE EMERGES. SO THIS AGAIN IS DATA FROM THE NATIONAL HEALTH INTERVIEW SURVEY, AND THESE ARE PREDICTED PROBABILITIES OF BINGE DRINKING FOR JUST THIS GROUP OF WOMEN AGED 30 TO 49 WHO ARE ESSENTIALLY IN THAT LATE 1970s, EARLY COVID-19 80s COHORT THAT ALL OF THESE STUDIES HAVE IDENTIFIED ARE A HIGH RISK GROUP FOR BINGE DRINKING. WE GRAPHED THE INCREASE IN BINGE DRINKING FROM THIS GROUP FROM 2006 TO 2018 BY AXE EASE AXEIS OF SOCIOECONOMIC INCOME. IT IS THIS GROUP, THE WOMEN WITH THE MOST INCOME, THAT IS INCREASING THE MOST. FOR WOMEN THAT ARE LIVING BELOW THE POVERTY LINE, THERE'S ALMOST NO INCREASE IN BINGE DRINKING. IT'S REALLY INCREASING AMONG THE MOST PRIVILEGED. AND WE ALSO EXAMINE THIS BY EDUCATION AND BY OCCUPATIONAL PRESTIGE. WE FOUND THE INCREASES IN FEMALE DRINKING IN MID LIFE ARE THE MOST CONCENTRATED AMONG WOMEN WITH THE HIGHEST INCOMES, THE HIGHEST LEVELS OF EDUCATION, INCLUDING GRADUATE DEGREES, AND WOMEN WITH THE HIGHEST LEVELS OF OCCUPATIONAL PRESTIGE ACROSS ALL OF THOSE DIFFERENT AXES. THAT IS WHO WAS DRIVING THE INCREASE IN BINGE DRINKING AMONG WOMEN IN THE UNITED STATES. SO IN ADDITION TO EXAMINING TRENDS IN BINGE DRINKING, WHICH IS MOST CONSISTENTLY -- BINGE DRINKING IS THE MOST CONSISTENTLY CAPTURED ALCOHOL USE INDICATOR ACROSS THESE DATASETS, WE'VE REALLY BEEN INTERESTING TO KNOW WHAT'S GOING ON WITH ALCOHOL USE DISORDERS. BINGE DRINKING IS A PROBLEMATIC INDICATOR OF ALCOHOL USE BUT NOT NECESSARILY INDICATIVE OF AN ALCOHOL USE DISORDER, THE PEOPLE WHO MIGHT NEED THE MOST SERVICES, MIGHT NEED THE MOST TREATMENT. AGAIN MONITORING THE FUTURE IS A REALLY VALUABLE RESOURCE FOR THIS, SO USING THAT, WE HAVE SCALES OF ALCOHOL USE DISORDERS IN MID LIFE, AND WE'VE BEEN ABLE TO EX-AP INTHIS ACROSS AGE 35, 40 AND 45 FOR A NUMBER OF DIFFERENT COHORTS. SO EACH OF THESE LINES REPRESENTS THE LIFE COURSE EXPERIENCE AT AGE 35, 40 AND 45 FOR INDIVIDUALS OBSERVED IN 2003 TO 2007, 2008 TO 2012 AND 2013 TO 2060. AT AGE 35, IT'S A GOOD STORY. WE FIND FOR ALCOHOL USE DISORDERS, EACH SUCCESSIVELY -- EACH GROUP OF 35-YEAR-OLDS THAT ARE ONLIED IN MORE RECENT HISTORY HAVE A LOWER PREVALENCE OF ALCOHOL USE DISORDER AT AGE 35. THIS DOTTED LINE HERE ARE THOSE WHO WERE OBSERVED BETWEEN 2003 AND 2016. BUT IF YOU LOOK AT THAT TRANSITION THROUGH MID LIFE TO 45, YOU SEE THAT THE OLDER COHORTS ARE DECLINING IN AUD PREVALENCE AT A MUCH FASTER RATE THAN THE YOUNGER COHORTS. SO THE YOUNGER COHORTS OF AGE 35-YEAR-OLDS, THEY BEGIN AT A LOWER RATE BUT THEY DON'T DECLINE AT THE SAME RATE AS THE OTHER COHORTS, AND, THEREFORE, WE MIGHT BE WORRIED THAT THIS IS A GROUP THAT'S NOT GOING TO HAVE THE SAME AGE-RELATED DECLINE IN ALCOHOL USE THAT WE COMMONLY SEE ACROSS THE LIFE COURSE, AND WE SEE A SIMILAR STORY WHETHER WE LOOK AT MILD, MODERATE OR SEVERE ALCOHOL USE DISORDERS. AND WHILE I DIDN'T SHOW THE GENDER DIFFERENCES IN THIS GRAPH, WHAT WE FIND IN THE MONITORING THE FUTURE DATA IS THAT THE CASE OF THIS SAME DECLINE, THE PACE OF THE DECLINE FOR THE MORE RECENTLY BORN COHORTS OF THOSE IN MID LIFE IS 17% SLOWER FOR WOMEN. AGAIN SUGGESTING THAT WOMEN ARE THIS INCREASINGLY HIGH RISK GROUP NOT ONLY FOR BINGE DRINKING BUT ALCOHOL USE DISORDERS. AND FINALLY, WE'VE ALSO BEGUN FORECASTING WHAT WE CAN EXPECT IN THE COMING DECADES. SO THIS REALLY IS -- AGAIN, THIS IS MONITORING THE FUTURE DATA, BUT WE'RE LITERALLY MONITORING THE FUTURE NOW. SHOWN HERE ARE OUR OBSERVED DATA ON BINGE DRINKING THROUGH 2020, SO THIS IS 2016 TO 2020, AND WE ARE PROJECTING WHAT WE EXPECT IN TERMS OF GENDER DIFFERENCES AND BINGE DRINKING THROUGH 2040. AND THIS IS DRITICALLY CRITICALLY IMPORTANT. LOOKING AT TRENDS IN THE PAST CAN BE ILLUMINATING FOR HISTORICAL ACTIVITY, BUT UNLESS IT HELPS US PLAN FOR THE FUTURE, IT'S OF LITTLE RELEVANCE TO PUBLIC HEALTH. SO WE REALLY ACTUALLY TRIED TO USE OUR DATA TO PROJECT INTO THE FUTURE. NOW OF COURSE COVID-19 IS A SALIENT NEW RISK FACTOR THAT WILL IMPACT THESE TRENDS, BUT THIS IS ASSUMING WE DO NOTHING, NOTHING CHANGES, WE JUST GO ALONG THE SAME TRAJECTORY AND USING THE SAME RISK FACTORS THAT INFORM ALCOHOL RELATED SURVEILLANCE TRENDS THUS FAR. SO WHAT CAN WE EXPECT? WE CAN EXPECT IF WE DO NOTHING THAT AGE 18 BINGE DRINKING WILL CONTINUE TO DECLINE. AND THEY'LL STILL BE SHOWN HERE IN THE SOLID LINES ARE THE UNADJUSTED MODELS, AND THAT'S ALL I'M GOING TO DISCUSS TODAY, BUT IF PEOPLE HAVE QUESTIONS, I'M HAPPY TO ANSWER THEM. SO DECLINES IN BINGE DRINKING, AGE 18, SIMILAR TO WHAT WE SAW IN THE OBSERVATIONAL DATA THROUGH THE MID PART OF THIS DECADE IN THE 2000s, WE CAN EXPECT GREATER GENDER CONVERGENCES THROUGH 2040 IN BINGE DRINKING AS THAT ACCELERATION DURING THE TRANSITION TO ADULTHOOD CONTINUES THAT UPWARD SLOPE. SO WHILE WE DO EXPECT THERE TO BE GENDER CONVERGENCES IN BINGE DRINKING AT AGE 18 FROM DECLINES, THOSE ARE GOING TO -- AS THESE DIFFERENT BIRTH COHORTS MOVE THROUGH THE LIFE COURSE. BUT ALL OF THIS IS PROBABLY BEGGING A CENTRAL QUESTION IN YOUR MIND: WHY? WHY ARE WOMEN IN MIDLIFE DRINKING MORE, WHY ARE THE TRENDS OCCURRING THE WAY THEY ARE, ESPECIALLY FOR THOSE AT THE HIGHEST LEVELS OF PRESTIGE AND STATUS, AND HOW DOES THAT INFORM OW WE THINK ABOUT ALCOHOL EPIDEMIOLOGY, FORMING THE FOUNDATION OF THE NEXT STAGE OF THIS WORK. AND THE ANSWERS THAT THIS HAS LED ME TO IN MY OWN WORK, REALLY BUILDING ON A FOUNDATION OF DECADES OF SCHOLARSHIP, IS THAT THROUGHOUT THE HISTORY OF ALCOHOL-RELATED CONSEQUENCES AT THE POPULATION LEVEL, THE ROLE OF ALCOHOL ACCEPTABILITY AND NORMS AND THE WAY IN WHICH THAT ACCEPTABILITY INTERSECTION HAS BEEN EXTRAORDINARILY POWERFUL AS A PREDICTOR OF POPULATION LEVEL RATES. AND JUST AS AN INTERESTING HISTORICAL EXAMPLE OF THIS, THIS IS FROM 1948. IT DEPICTS GEORGE WASHINGTON, HE'S TOASTING HIS OFFICERS, WE SEE WASHINGTON HOLDING A CLASS AND ON THE TABLE, THERE'S A SUPPLY OF LIQUOR. IN 1878, THIS PICTURE WAS REENGRAVED, REFLECTING THE INFLUENCE OF THE TEMPERANCE MOVEMENT. WASHINGTON NO LONGER HOLDS ANY ALCOHOL AND THE ALCOHOL HAS BEEN REPLACED BY A HAT. SO WHAT THIS IS A LENS INTO IS THE WAY IN WHICH ALCOHOL ACCEPTABILITY AND ALCOHOL POLICY INTERSECT IN WAYS THAT PREDICT WHAT'S GOING TO HAPPEN WITH POPULATION LEVEL TRENDS IN ALCOHOL CONSUMPTION. AND WE'VE SEEN THIS TIME AND TIME AGAIN IN ALCOHOL EPIDEMIOLOGY INCLUDING MONITORING THE FUTURE. IN MY WORK, I'VE REALLY TRIED TO FOCUS ON WHAT DRIVERS HISTORICAL TRENDS IN POPULATION LEVEL ALCOHOL CONSUMPTION. AND WHILE EVERYONE WHO'S HERE RECOGNIZES THE IMPACT OF ALCOHOL POLICY, THE ROLE OF ALCOHOL ACCEPTABILITY AS BOTH A DRIVER AND A CONSEQUENCE OF THAT POLICY AND A MECHANISM THAT DRIVES POPULATION LEVEL CHANGE IS UNDERAPPRECIATED. SO IN MY WORK IN MONITORING THE FUTURE, FOR EXAMPLE, WE DEMONSTRATED THAT THE PROPORTION OF EACH BIRTH COHORT, THE DISAPPROVES OF THINGS LIKE WEEKEND BINGE DRINKING, AS THAT PROPORTION INCREASES -- DECREASES, THE LOG INCREASES. THIS CONTROLS FOR THE ADOLESCENT'S ONLY ATTITUDE TOWARDS DRINKING. IF YOU ARE IN A BIRTH COHORT THAT IS HIGHLY DISAPPROVING OF BINGE DRINKING YOU'RE MORE PROTECTED AGAINST BINGE DRINKING INDEPENDENT OF WHETHER YOU'RE IN A FAMILY, A NEIGHBORHOOD OR A SITUATION WHERE ALCOHOL IS READILY ACCESSIBLE AND THERE ARE LITTLE SANCTIONS TO USE, INDICATING THAT THE POWER OF THE BIRTH COHORT TO DRIVE THESE SOCIAL NORMS AND THE WAY IN WHICH THEY PREDICT POPULATION LEVEL CHANGE IS A REALLY POWERFUL DETERMINANT OF THE DISTRIBUTION OF ALCOHOL USE AT A POPULATION LEVEL. AND THE ROLE OF THESE BROADER NORMS AND STRUCTURES FOR WOMEN ALSO ARE INDICATIVE OF THE GENDER DIFFERENCES THAT WE SEE AND THE CONVERGENCES AND DIVERGENCES AND GENDER DIFFERENCES THAT WE SEE. SO FOR EXAMPLE, USING THE WORLD MENTAL HEALTH SURVEY, IN A PAPER IN 2010, CONSTRUCTED A MEASURE OF GENDER ROLE -- THE PROPORTION WHO ARE USING -- TO GET HIGHER LEVELS OF EDUCATION, AND WHAT THEY FOUND IS THAT AS THE GENDER ROLE TRADITIONALITY INCREASE, GENDER ROLES ARE MORE TRADITIONAL FOR WOMEN, THEIR ODDS OF SUBSTANCE USE DISORDER DECREASES. SURGING THAT ONE WAY IN SUGGESTING ONE WAY WE CAN THINK ABOUT THESE TRENDS IN BINGE DRINKING FOR WOMEN AS INCOME AND PRESTIGE INCREASES, IS THAT THEY ARE CONSISTENTLY OCC OCCUPYING SPACES THAT WERE TRADITIONALLY MALE-DOMINATED AND AS THE ACCEPTABILITY OF HEAVY ALCOHOL USE IS ALSO INCREASING, SUGGESTING THAT UNDERSTANDING THE SOCIOLOGICAL PHENOMENON THAT UNDERLIE THE POSITIONS WE TAKE IN SOCIETY ARE AN IMPORTANT DETERMINANT OF HOW WE'RE GOING TO CONSIDER WAYS TO IMPROVE POPULATION HEALTH THROUGH ALCOHOL CONTROL. BUT OBVIOUSLY IT'S CRITICAL TO CONSIDER COVID-19. IT'S IMPORTANT TO CONSIDER HOW THESE TRENDS ARE ALL GOING TO BE SHAPED IN THE COMING YEARS AND DECADES THROUGH THE LENS OF THIS PANDEMIC THAT WE'RE ALL LIVING THROUGH. BUT WHAT I HOPE I'VE CLEARLY ARTICULATED IN THIS TALK IS THAT THE ANSWER TO THAT QUESTION CANNOT BE ANALYZED BY ONLY CONSIDERING THE PANDEMIC CONTEXT. ACTUALLY HISTORICAL VARIATION OF ALCOHOL CONSUMPTION IS MUCH LONGER STANDING THAN 2020. AND THE EXISTING AGE, PERIOD AND COHORT EFFECTS IN ALCOHOL USE WILL NEED TO BE EMBEDDED WITH AND MAY POTENTIATE THE EFFECTS OF COVID-19. SO AT JUST ONE EXAMPLE, WE HAVE BEEN CONSIDERING HYPOTHETICAL SCENARIOS IN WHICH COVID-19 MAY CHANGE ALCOHOL TIME TRENDS AND DEVELOPING METHODOLOGICAL AND STATISTICAL TOOLS THAT WILL HELP US TEASE APART LONG TERM AGE, PERIOD AND COHORT EFFECTS FROM LOCAL AND SUDDEN FLUCTUATIONS. TWO COHORTS MOVING THROUGH TIME, COHORTS OF YOUNG ADULTS AND COHORTS OF MIDDLE ADULTS, AND WE MIGHT ANTICIPATE THAT THE MIDDLE AGED ADULTS ARE GOING TO BE DRINKING MORE THAN THE YOUNG ADULTS, GIVEN THE TIME TRENDS THAT WE'VE BEEN OBSERVING IN RECENT YEARS. BUT WE MIGHT ANTICIPATE THAT FOR THESE DIFFERENT BIRTH COHORTS, THERE WILL BE AN INTERSECTION WITH LOCAL AGE EFFECTS DUE TO COVID-19, WHERE FOR YOUNG ADULTS, WE MIGHT PREDICT THAT COVID-19 WILL ACTUALLY DECREASE ALCOHOL CONSUMPTION COMPARED TO WHAT WE WOULD HAVE PREDICTED IN A NON-PANDEMIC CONTEXT IF YOUNG ADULTS ARE REMOVED FROM COLLEGE CAMPUSES, IF THEY'RE SPENDING MORE TIME AT HOME AND LUS UNSUPERVISED TIME WITH YOUNG ADULTS. WHEREAS FOR MIDDLE ADULTS, WE MIGHT -- DO TO INCREASED STRESSFUL LIFE EVENTS, BEREAVEMENT AND OTHER STRESSFUL EXPERIENCES. SO IN THIS, THE ONGOING LONG TERM COHORT AND PERIOD EFFECTS WITH LOCALIZED PERIOD EFFECTS THAT THEMSELVES ARE INTERACTING WITH AGE. UNTIL WE UNDERSTAND ALL OF THOSE TIME DYNAMICS TOGETHER, WE WON'T GET GOOD QUANTITATIVE ESTIMATES OF THE EFFECT OF COVID-19 ON ALCOHOL USE. SO REALLY INTEGRATING FRAME WORKS WITH THE ABILITY TO DETECT THESE CHANGES IN LOCALIZED PERIOD EFFECTS THAT MAY THEMSELVES INTERSECT WITH AGE IS THE NEXT STEP OF OUR RESEARCH. AND FINALLY, I'M JUST GOING TO END THIS TALK BY AGAIN STEPPING BACK AND THINKING ABOUT HOW COVID-19 HAS AMPLIFIED EXISTING INEQUALITIES AND EXISTING KIND OF PUBLIC HEALTH PRINCIPLES, RIGHT? SO WHEN WE WERE INTRODUCING THE BOOK, WE WROTE THIS COMMENTARY FOR AMERICAN JOURNAL OF PUBLIC HEALTH, AND IN THAT PAPER, WE SAID, WHEN WE LOOK ACROSS THE LAST CENTURY TO THE FACTORS THAT HAVE DRAMATICALLY IMPROVED THE LIVES 69 OF THE POPULATION, VERY FEW HAVE BEEN PERSONALIZED FOR PRECISE. AND WHAT WE'VE SEEN IN COVID-19 IS THIS PHENOMENON PLAY OUT. WHAT HAS CONTROLLED THE PANDEMIC HAS BEEN INTERVENTIONS THAT ARE NEITHER PERSONALIZED OR PRECISE. THEY ARE POPULATION LEVEL TO SHIFT THE CURVE. THAT'S THE SAME REFRAIN THAT WE'VE -- I THINK THAT SAME PRINCIPLE CAN BE APPLIED TO ALCOHOL EPIDEMIOLOGY. WHEN WE LOOK ACROSS WHAT'S GOING TO HAPPEN IN THE NEXT CENTURY, THE NEXT DECADES OF CONTROLLING ALCOHOL-RELATED HARM IN THE POPULATION, WE NEED TO LOOK TOWARDS INTERVENTIONS THAT ARE NEITHER PERSONALIZED NOR PRECISE. THAT ARE BOLD AND BROAD AND SHIFT THE ENTIRE POPULATION CURVE TOWARDS A MORE HEALTHY LEVEL OF ALCOHOL CONSUMPTION FOR THE POPULATION. THAT'S NOT EASY. IT'S NOT AN EASY POLITICAL SELL, AS WE'VE SEEN WITH COVID-19. THIS HAS TO DO WITH THE PREVENTION PARADOX. MOST PEOPLE WILL NOT BENEFIT FROM PREVENTION EFFORTS, RIGHT? WE'VE SEEN THAT WITH COVID-19. LARGE NUMBERS OF PEOPLE WHO WILL NOT BENEFIT STILL NEED TO PARTICIPATE FOR POPULATION HEALTH TO BE MAXIMIZED. AND IT'S THOSE KIND OF PRINCIPLES, THAT WILL FORM THE FOUNDATION OF THE PUBLIC HEALTH WORK I PLAN TO DO IN THE COMING DECADES, HOPEFULLY WITH THE SUPPORT FROM NIAAA. SO I WOULD LIKE TO THANK THE FUNDERS OF MY WORK, INCLUDING NIAAA, BUT OTHER NIH INSTITUTES AS WELL AND THE CDC, AS WELL AS MY DEPARTMENT -- THE COLUMBIA UNIVERSITY DEPARTMENT OF EPIDEMIOLOGY. THANK YOU VERY MUCH. >> SO THANK YOU, KATHERINE. THAT WAS A SUPERB TALK, AND I LEARNED A LOT MYSELF FROM YOUR PRESENTATION, AND I'M PARTICULARLY INTRIGUED, OF COURSE, WITH THE COHORT EFFECTS AND HOW THAT'S IMPACTING A LOT OF THE MEASURES THAT WE'RE TAKING, AND IT'S CERTAINLY GOING TO HAVE IMPORTANT CONSEQUENCES FOR WHERE WE DIRECT OUR ENERGY PREVENTION AND INTERVENTION IN THE FUTURE, SO I THANK YOU PROFUSELY FOR ALL THAT. THERE ARE A COUPLE QUESTIONS SHOWING UP ON THE SCREEN BUT I'M GOING TO ASK YOU ONE OF MY OWN FIRST, BECAUSE IT'S MY PREROGATIVE, SO TO SPEAK. WHAT ABOUT WHAT I WOULD NEBULOUSLY CALLED CULTURE? WE HAD CONVENED A GROUP ON BINGE DRINKING SOME TIME AGO, AND ONE OF THE THINGS DOVETAILS A LITTLE BIT WITH WHAT MARC IS GOING TO TALK ABOUT, BUT YOU KNOW, WE HISTORICALLY, IN MOVIES AND TV SHOWS, WE EXTOL THE CHAP WHO CAN SAUNTER UP TO THE BAR OR THE WOMAN WHO CAN SAUNTER UP TO THE BAR, DOWN FIVE SHOTS, PICK UP THE DART AND HIT THE BULL'S-EYE OKAY, AND I THINK MARC IS GOING TO TELL US THAT LOW RESPONSE INDIVIDUALS LIKE THAT ARE THE ONES WHO GO ON TO AN ALCOHOL USE DISORDER LATER IN LIFE. SO IN YOUR LAST MESSAGE THERE, DO WE HAVE TO CHANGE CULTURE AND ATTITUDES IN THIS PROPORTION OF DISAPPROVAL, WILL THAT BE A PUBLIC HEALTH WAY OF WEARING A MASK, SO TO SPEAK? >> YES, I THINK SO. THAT HAS BEEN -- I THINK THE EVIDENCE IS CERTAINLY CLEAR THAT ALCOHOL CULTURE AND ALCOHOL ATTITUDES DO HAVE SORT OF AN INDEPENDENT EFFECT ON POPULATION DISTRIBUTIONS OF ALCOHOL CONSUMPTION OVER AND ABOVE OTHER TYPES OF POPULATION CONTROL STRATEGIES. FOR EXAMPLE, WHEN YOU LOOK ACROSS THE 1980s AND 1990s, WHERE WE SAW THIS BIG DECLINE IN ADOLESCENT BINGE DRINKING, AND IT WAS DURING THIS TIME PERIOD IN WHICH WE WERE RAISING THE MINIMUM LEGAL DRINKING AGE AND THERE WERE ALL SORTS OF OTHER EFFORTS TO REDUCE UNDERAGE DRINKING. WE HAVE FOUND IN OUR ANALYSES THAT THAT EXPLAINS ABOUT HALF OF THE VARIATION IN DRINKING AMONG ADOLESCENTS, MEANING THAT THERE'S A WHOLE 'NOTHER HALF OF THAT VARIATION LEFT TO BE EXPLAINED AND WE THINK A LOT OF THAT HAS TO DO WITH ATTITUDES AND CULTURE, AND SO UNDERSTANDING WHAT DRIVES CHANGES IN THOSE THINGS OVER AND ABOVE KIND OF POLICY LEVERS I THINK IS A REALLY IMPORTANT GOAL FOR BOTH KIND OF WITHIN GEOGRAPHIC AREA, CHANGE, AS WELL AS TEMPORAL CHANGE AND PREDICTING IT. >> SO THERE WAS ONE QUICK QUESTION FROM SOME OF MY FRIENDS, TWO OF THEM ACTUALLY. ONE WAS ABOUT WHEN ARE WE GOING TO STOP USING THE WORD "ABUSE" IN OUR REPORTS AND WEBSITE, SO ON AND SO FORTH. THAT'S FROM TIFFANY HALL, FROM RECOVER ALASKA. TIFFANY, WE'VE ALREADY BEEN PURGING FOR THE LAST YEAR OR TWO, AND WE JUST HAVE REDONE OUR WEBSITE. I'M NOT GOING TO DWELL ON THIS, BUT YOU'LL NOTICE IN MY PRESENTATION, I NEVER USED THE WORD ABUSE, I USED MISUSE. IT'S IN THE TITLE OF OUR INSTITUTE. WE KARNLT CAN'T CHANGE THAT EXCEPT AS AN ACT OF CONGRESS, AS YOU'RE WELL AWARE. IF WE'VE SCREWED UP, LET US KNOW. THEN MICHAEL HOFFER HAS ONE FOR YOU, KATHERINE. U.S. ADOLESCENTS HAVE MORE ACCESS TO A WIDER VARIETY OF PSYCHOACTIVE SUBSTANCES THAN PREVIOUS GENERATIONS. IS THE DECREASE IN ALCOHOL USE IN HIGH SCHOOL STUDENTS MERELY A SUBSTITUTION EE FECT FOR OTHER INHERENTLY REWARDING SUBSTANCES? >> THIS QUESTION COMES UP A LOT, AND FROM OUR -- THE WAY WE LOOK AT THAT EPIDEMIOLOGICALLY IS TO COMPARE THE TIME TREND IN ALCOHOL USE TO THE TIME TRENDS IN OTHER SUBSTANCES, AND IN FACT, THE TIME TRENDS DO NOT CORRESPOND. SO IT'S NOT WHEN YOU SEE AN INCREASE IN ALCOHOL, YOU SEE AN INCREASE IN OTHER PSYCHOACTIVE SUBSTANCES. IN FACT IN THE LAST 20 YEARS, MOST SUBSTANCES IN -- FOR EXAMPLE, CANNABIS USE, ELECTRONIC CIGARETTE USE, VAPING, THOSE TYPES OF PRODUCTS. YOU WOULD EXPECT THE DECLINE IN ALCOHOL USE STARTED WELL BEFORE INCREASES IN THINGS LIKE OPIOID USE IN THE POPULATION, WHICH ITSELF HAS BEEN DECLINING AMONG ADOLESCENTS FOR OVER 10 YEARS NOW. SO WE DON'T SEE ANY COMPELLING EVIDENCE THAT THE DECLINE IN ALCOHOL CONSUMPTION IS BEING REPLACED OR SUBSTITUTED BY ANY OTHER PSYCHOACTIVE SUBSTANCE, ALTHOUGH OTHER PSYCHOACTIVE SUBSTANCES HAVE THEIR OWN DYNAMIC TIME TRENDS. I JUST HAVEN'T SEEN EVIDENCE THAT THEY'RE INVERSE LIQUOR LATED. >> GREAT. AND THEN -- SKIPPING AROUND ON ME. RICHARD JOHNSON: DID THE PREFERENCE OF ALCOHOLISM INCREASE DURING THE 20TH CENTURY AND ARE THERE PUBLICATIONS THAT LOOK AT THE RATE OVER THE VARIOUS DECADES? >> I ASSUME THAT MEANS ALCOHOL USE DISORDER? I AM NOT AWARE OF POPULATION SORT OF COMMUNITY-BASED DATA SOURCES THAT HAVE LOOKED AT TIME TRENDS IN ALCOHOL USE DISORDER IN COMPARABLE ENOUGH -- WHERE YOU CAN STITCH TOGETHER DURING THE 20TH 20TH CENTURY. WE HAVE BEEN ABLE TO RETROSPECTIVELY SORT OF TO BELIEVE WHEN WE USE THOSE TYPES OF METHODS, WE DO SEE AN INCREASE IN ALCOHOL USE DISORDERS, ESPECIALLY AFTER WORLD WAR II, OF COURSE TAKES THAT WITH A GRAIN OF SALT BECAUSE WE HAVE SEEN WITH OTHER TYPES OF HEALTH OUTCOMES LIKE DEPRESSION, FOR EXAMPLE, OFTENTIMES WHEN YOU HAVE RETROSPECTIVE REPORTING, YOU SEE -- DRINKING BETTER THAN THE OLDER GENERATIONS WHEN THEY WERE THAT GENERATION'S AGE. SO I THINK WHAT I WOULD SAY IS THE AVAILABLE ESTLED SUGGESTS THAT THERE IS INCREASE IN ALCOHOL USE DISORDER KIND OF POST WORLD WAR II, 20TH CENTURY, BUT I THINK IT'S NOT DEFINITIVE. >> GREAT. JAVIER BALISTER SAYS GREAT PRESENTATION, I WAS WONDERING IF YOU'VE TAKEN INTO ACCOUNT IN YOUR STUDIES THE NUMBER OF CHILDREN THAT WOMEN AND MEN HAVE AS A FACTOR THAT COULD EXPLAIN SOME OF THE CHANGES IN THE GENDER EFFECT. I WAS THINKING MORE PRECISELY IN THE ROLE OF PROGESTERONE WITH SOME POTENTIAL >> NO, I THINK THAT'S A REALLY INTRIGUING IDEA. WE HAVE TAKEN INTO ACCOUNT NULLA PARITY, CERTAINLY IN THE LAST 40, 50 YEARS THERE'S BEEN INCREASE IN THE PROPORTION OF WOMEN WHO DON'T HAVE CHILDREN AND DELAY IN THE AGE OF CHILDBEARING, AND WE'VE TAKEN THAT INTO ACCOUNT AND CHANGES IN DRINKING IF, AND CERTAINLY THAT DOES PREDICT SOME OF THE CHANGE IN DRINKING, BUT THAT'S NOT -- THAT WOULDN'T HAVE THE SAME MECHANISM, I THINK, THAT YOU WERE DESCRIBING, AND WE HAVEN'T REALLY TAKEN INTO ACCOUNT THE AVERAGE FAMILY SIZE, SO I THINK THAT'S A GREAT IDEA. >> THEN KEN LEONARD WANTS TO KNOW, TO WHAT EXTENT DO SOME OF THE RECENT INCREASES IN WOMEN'S DRINKING REFLECT REDUCED -- THE INCREASED AGE OF HAVING CHILDREN, PARTICULARLY IN MIDDLE, UPPER -- SORRY -- IN MIDDLE UPPER SES. >> SO I THINK I WAS KIND SPEAKING TO THAT IN THE LAST QUESTION TOO. WE HAVE EXAMINED THAT AS A MEDIATING MECHANISM IN MONITORING THE FUTURE AND QUANTIFIED THE PROPORTION OF THE ACCELERATION IN DRINKING DURING THAT TRANSITION TO ADULTHOOD THAT WE SEE IN RECENT BIRTH COHORTS THAT'S DUE TO EACH OF THESE DIFFERENT FACTORS, INCLUDING THINGS LIKE AGE OF MARRIAGE AND AGE OF CHILDBIRTH, AND INCLUDING OTHER -- WHICH HAS CHANGED DRAMATICALLY AND CERTAINLY ALL OF THEM HAVE A SIGNIFICANT -- CERTAINLY I THINK THAT DOES EXPLAIN SOME OF THE INCREASES THAT WE'RE SEEING BUT NOT IN TOTALITY. >> THEN ANOTHER GOOD ONE FROM TIFFANY HALL. THE SES LEVELS FOR WOMEN BINGE DRINKING, DO THESE NUMBERS INCLUDE PEOPLE EXPERIENCING HOMELESSNESS? OUR TOWN CON FLAITS HOMELESSNESS AND AUD, AND EVEN THOUGH I KNOW SOME OF THESE NUMBERS CORRELATING WEALTH AND ALCOHOL USE, IT'S HARD TO DISPEL THE NOTION THAT PEOPLE SEE IT ON THE CORNER, INTOXICATED -- IT'S A GOOD QUESTION ABOUT PUBLIC PERCEPTION VERSUS THE NUMBERS. >> YEAH, I THINK THAT'S A REALLY IMPORTANT POINT. CERTAINLY A LOT OF THESE NATIONAL SURVEYS ARE HOUSEHOLD SAMPLES SO THEY'RE NOT GOING TO CAPTURE THE MOST AT-RISK POPULATIONS SO I THINK THAT'S AN IMPORTANT POINT THAT I PROBABLY SHOULD HAVE MADE THAT ALL OF OUR ESTIMATES ARE LIKELY AN UNDERESTIMATE OF THE TOTALITY OF DRINKING PROBLEMS IN THE POPULATION. I THINK THAT'S A REALLY GOOD POINT. I THINK MUCH MORE RESEARCH NEEDS TO BE DONE IN ORDER TO DI SPELL THE KINDS OF STIGMA ON UNHOUSED PEOPLE. THANK YOU FOR MENTIONING THAT. >> TOM DEHUGHES. REGARDING THE TRADITIONAL -- GENDER ROLE NORMS WHERE -- THIS IS -- THERE'S A FLAW IN OUR WORK HERE WITH THESE MESSAGES COMING IN, WHICH IS THAT I CANNOT READ THEM WHILE IT'S JUMPING AROUND. SO DEB, WE'VE GOT TO DO SOMETHING ABOUT WHEN I'M SPEAKING, NOT TO SEND MORE. REGARDING THE TRADITIONAL GENDER NORMS, WHEREAS THESE REDUCE HARMFUL ALCOHOL USE AND OVERALL USE AMONG WOMEN IN VARIOUS CULTURAL CONTEXTS, WHAT ABOUT WOMEN WHO DO NOT ADHERE TO SUCH NORMS, LESBIAN AND OTHER SEXUAL MINORITY WOMEN? WOULDN'T THIS HELP EXPLAIN INCREASED RISK IN THIS GROUP? >> I THINK THAT'S A GREAT POINT, AND THAT'S SOMETHING THAT, YOU KNOW, SEXUAL ORIENTATION IS NOT ROUTINELY CAPTURED ON A LOT OF THESE NATIONAL STUDIES AS WELL, SO WE WERE NOT ABLE TO TEASE APART, YOU KNOW, KIND OF GENDER ROLES AND ADHERENCE TO THEM IN THESE STUDIES, BUT I THINK IT'S CRITICALLY IMPORTANT AND I THINK LOOKING AT TRENDS IN THOSE OVER TIME WOULD BE REALLY ELIMINATING. >> GREAT. -- MARTINEZ WRITES. THE USE OF WIDE RANGING PUBLIC POLICIES TO CURB COVID-19 APPEARS DIFFICULT TO SUSTAIN FOR LONG PERIODS, MORE THAN A FEW MONTHS. WOULDN'T THIS -- THAT POLICIES ON ALCOHOL WOULD NOT BE SUSTAINABLE FOR MORE THAN A FEW MONTH AS WELL? >> HOPEFULLY NOT. WE'VE BEEN ABLE TO KEEP MINIMUM LEGAL DRINKING AGE AROUND FOR A WHILE. >> HOW ARE YOU INCORPORATING COLLABORATING WITH PEOPLE WHO HAVE LIVED EXPERIENCES OF ALCOHOL MISUSE AND RECOVERY IN YOUR RESEARCH? GOOD QUESTION. >> THAT'S A GREAT QUESTION. YOU KNOW, CERTAINLY IN A LOT OF OUR WORK, WE TRY AS MUCH AS WE CAN WITH COMMUNITY MEMBERS AND COMMUNITY GROUPS THAT ARE DEALING WITH ALCOHOL USE DISORDER AND UNFORTUNATELY ALCOHOL USE DISORDER IS SOMETHING THAT TOUCHES A LOT OF FAMILIES SO HAVING LIVED EXPERIENCE WITHIN A RESEARCH GROUP IS PROBABLY -- NOT HAVING LIVED EXPERIENCE WITHIN A RESEARCH GROUP IS PROBABLY THE EXCEPTION RATHER THAN THE RULE, BUT YOU KNOW, I CERTAINLY THINK IT'S REALLY CRITICALLY IMPORTANT TO CONTINUOUSLY ENGAGE WITH COMMUNITIES OF PEOPLE WHO ARE ACTIVELY EXPERIENCING ALCOHOL USE DISORDER AND RECOVERING FROM THEM. IT'S BROUGHT A LOT OF NUANCE AND VALUE TO MY WORK, SO THANK YOU FOR RAISING THAT. I THINK IT'S IMPORTANT. >> SHAMORA ASKS, IS THE CHANGE IN FARMING WITH CONVERTING FOOD PRODUCING LAND TO GRAPE AND WINE PRODUCTION AND TAKING INTO CONSIDERATION MARKETING WINE TO WOMEN AND INCREASED PRODUCTION, AVAILABILITY AND REDUCED -- ON THE INCREASE OF ALCOHOL USE FOR WOMEN IN PARTICULAR? >> YEAH, I TOTALLY AGREE, AND THAT'S SOMETHING I'M REALLY INTERESTED IN, IT IS ONE OF THESE CHICKEN AND EGG ISSUES. CERTAINLY WE KNOW THE NUMBER OF ALCOHOL PRODUCTS THAT ARE MARKETED TOWARDS OR BRANDED FOR WOMEN HAS INCREASED QUITE A BIT, ESPECIALLY IN THE LAST 10 YEARS. SKINNY COCKTAILS AND OTHER TYPES OF PRODUCTS THAT ARE EITHER IMPLICITLY OR EXPLICITLY MARKETED TOWARDS WOMEN, AND IS THAT DRIVING THE DEMAND OR IS THE DEMAND DRIVING THE PRODUCT OR IS IT A LITTLE BIT OF BOTH, THE ALCOHOL INDUSTRY IS TAKING NOTICE IN THE INCREASES IN CONSUMPTION AMONG WOMEN. I HAVEN'T ACTUALLY LOOKED AT THE CONVERSION OF LAND TO WINE PRODUCTION. CERTAINLY WE KNOW THAT THERE IS AN INCREASE AMONG BEVERAGE TYPES THAT ARE CONSUMED IN THE UNITED STATES, THERE HAS BEEN INCREASE IN WINE CONSUMPTION REFLECTIVE OF THE INCREASED TRENDS IN CONSUMPTION AMONG WOMEN. BUT A MORE PREHEN SIEVE LOOK AT COMPREHENS IVE LOOK WOULD BE INTERESTING SO THANK YOU FOR SUGGESTING IT. >> SO WE WILL SAVE THESE MESSAGES AND GET THEM TO KATHERINE, SHE WILL HAVE YOUR EMAILS AND SHE'LL BE ABLE TO RESPOND TO YOU BY EMAIL. BUT MICHAEL MILLER WRITES, THERE WAS NO MENTION AT ALL ABOUT THE TELESCOPING EFFECT IN WHICH WOMEN DEVELOP MEDICAL COMPLICATIONS AFTER SHORTER-TERM EXPOSURE AND LOWER LEVEL EXPOSURE VERSUS MEN RELATIVE TO YOUR GENDER DATA. THIS IS PROBABLY A WHOLE DIFFERENT TALK BUT MAYBE A QUICK ANSWER. >> THE TELESCOPING LITERATURE HAS BEEN PREDOMINANTLY DERIVED FROM CLINICAL SAMPLES AND THERE IS A BIT OF A CLINICIAN'S TO TELESCOPING. I'VE DONE SOME WORK EXAMINING WHETHER THE TELESCOPING PHENOMENON EXISTS IN COMMUNITY-BASED SAMPLES. SUFFICE TO SAY IT'S A MORE COMPLICATED PICTURE WHEN YOU LOOK AT NON-TREATMENT-SEEKING SAMPLES IN TERMS OF HOW AND WHERE TELESCOPING OCCURS AND THE BIRTH COHORT TRENDS IN THE TELESCOPING EFFECT ITSELF. SO I'D BE HAPPY TO SEND REFERENCES ON THAT. >> ALL RIGHT. WELL, THANK YOU AGAIN TORE A WONDERFUL TALK AND GREAT ANSWERS TO THE QUESTIONS, AND GREAT QUESTIONS FROM EVERYONE, AND I'M SORRY WE CAN'T GET TO THEM ALL, BUT WE MOVED A AS QUICKLY AS WE COULD AND KATHERINE DID A GREAT JOB. ALL RIGHT. IT IS NOW MY PLEASURE TO INTRODUCE OUR NEXT SPEAKER. DR. MARC SCHUCKIT. DR. SCHUCKIT IS THE DISTINGUISHED PROFESSOR OF PSYCHIATRY AT THE UNIVERSITY OF CALIFORNIA-SAN DIEGO. THROUGHOUT HIS DISTINGUISHED CAREER, HIS RESEARCH HAS FOCUSED ON THE IDENTIFICATION OF PREDISPOSING FACTORS FOR HEAVY DRINKING AND ALCOHOL PROBLEMS AND CONDUCTING STUDIES THAT INVESTIGATE BOTH GENETIC AND ENVIRONMENTAL FACTORS RELATED TO ALCOHOL USE DISORDER. IN ADDITION TOLL -- HE HAS MADE SIGNIFICANT CONTRIBUTIONS DEVELOPING DIAGNOSTIC CRITERIA FOR ALCOHOL AND OTHER SUBSTANCE USE DISORDERS. I JUST WANT TO ADD THAT I'VE KNOWN MARC FOR A LONG TIME, AND HE'S ACTUALLY ONE OF MY HEROS IN THE ALCOHOL FIELD, AND HE STILL LOOKS YOUNGER THAN I DO, SO I'M REALLY HAPPY TO HAVE HIM BE PART OF OUR SYMPOSIUM. WE WILL NOW BEGIN DR. SCHUCKIT'S PRESENTATION, "ALCOHOL USE DISORDER RISK, DIAGNOSES AND COURSE IN A 35--YEAR-OLD PROSPECTIVE STU TI STUDIES ALONG WITH IMPLICATIONS FOR INTERVENTION. MARC, IT'S ALL YOURS. >> HELLO, EVERYONE. I'M MARC SCHUCKIT FROM THE UNIVERSITY OF CALIFORNIA-SAN DIEGO. AND I AM GOING TO SHARE WITH YOU TODAY SOME RESEARCH THAT I HAVE BEEN DOING PRETTY MUCH SINCE THE NIAAA WAS THE NIAAA. AND IN FACT, SOME OF WHAT I'LL TALK ABOUT ACTUALLY BEGAN WITH THE PRECURSOR OF THE NIAAA. SO PRETTY MUCH THIS IS AN EXPOSITION ON HOW I GREW UP WITH THE NIAAA AND HOW GRATEFUL I AM FOR ALL OF THE HELP THAT I'VE RECEIVED OVER THE YEARS. I'M GOING TO EMPHASIZE TWO PROSPECTIVE STUDIES THAT I'VE BEEN INVOLVED WITH. ONE THAT BEGAN IN 1978, AND IT'S CALLED THE SAN DIEGO PROSPECTIVE STUDY, AND THE OTHER, THE COLLABORATIVE STUDY ON GENETICS OF ALCOHOLISM. AND I WILL BE BRINGING IN SOME DATA FROM A FEW ADDITIONAL STUDIES, BUT IT'S IMPORTANT TO NOTE, THIS IS A RABID OVERVIEW, ALMOST RAPID OVERVIEW WITH WONDERFUL COLLABORATORS AND WITH THE HELP AND SUPPORT OF THE NATIONAL INSTITUTE ON ALCOHOLISM AND ALCOHOL ABUSE. MY WORK ACTUALLY BEGAN AS PART OF A STUDY WHEN I WAS A MEDICAL STUDENT, AND THIS STUDY WAS FUNDED BY THE PRECURSOR OF THE NIAAA, WITH JACK MENDELSOHN. AND JACK BECAME A MENTOR AND A VERY DEAR FRIEND OVER THE YEARS. MY WORK CONTINUED AS I HAD THE OPPORTUNITY OF WORKING WITH DR. ENOCH GORDIS AND DR. GEORGE KOOB. HE WAS DOING WORK DOWN THE STREET NEAR THE UNIVERSITY OF CALIFORNIA-SAN DIEGO, AND HE CONTINUES TO BE PART OF THE IMPORTANT WORK THAT I DO. AND ESPECIALLY I WANT TO PAY TRIBUTE TO TO DR. T.K. LI, AND OF THE MANY WONDERFUL THINGS ABOUT T.K. I REMEMBER, IT'S THIS SMILE THAT JUST ABSOLUTELY TRUNKLES. MY WORK, THEREFORE S A TRIBUTE TO THESE LEADERS WHO HAVE IMPACTED SO MUCH ON MY LIFE. AS WELL AS THE AWESOME STAFF THAT I'VE HAD THE CHANCE TO INTERACT WITH OVER THE YEARS, ESPECIALLY IN RECENT YEARS,% ANTONIO AS WELL AS JOHN. WHAT I'M GOING TO BE PRESENTING IS NEARLY 50 YEARS OF WORK AND IT IS BASED PRIMARILY ON THE SAN DIEGO PROSPECTIVE STUDY. SO WE CAN BEGIN BY JUST GIVING YOU A BRIEF OVERVIEW. THIS WAS A STUDY THAT BEGAN IN 1978 WITH 453 DRINKING BUT NOT ALCOHOL USE DISORDER. NOT ABUSE OR DEPENDENT, MALE STUDENTS. ABOUT AGE 20 OR 21. AS THE STUDY PROGRESSED AND AS WE WENT IN TO A FOLLOW-UP PHASE OF THE ORIGINAL STUDIES THAT BEGAN IN '78, WE WERE FORTUNATE ENOUGH, PROPORTIONATE ENOUGH TO BE ABLE TO BRING IN THE WIVES AS WELL AS CHILDREN, BOTH SONS AND DAUGHTERS OF OUR ORIGINAL SUBJECTS. EVERYTHING ADDS UP NOW TO ABOUT 1600 PEOPLE. AND OVER THE YEARS, WE'VE BEEN ABLE TO STUDY BOTH WITH GENES AND ENVIRONMENT, AND BECAUSE THESE SUBJECTS HAVE BEEN SO GOOD TO US, EVEN AT 35-YEAR FOLLOW-UP, AND THAT FOLLOW-UP WAS BASICALLY ONGOING NOW, WE STILL HAVE 90% OF THE ORIGINAL PRO BANS WITH US. SO SOME OF THE DATA I'M GOING TO PRESENT WILL BE BACKGROUND ON WHAT WE'VE DONE, AS WELL AS THE FOLLOW-UP AS IT'S BEEN DONE WITH THE PROBANDS WHO ARE NOW ABOUT AGE 55. THE PROBANDS ARE OF COURSE THE INDIVIDUALS WHO FUNDED -- WHO FOUNDED, I SHOULD SAY, THE FAMILIES THAT WOVE BEEN FOLLOWING OVER THE YEARS AND THEN EXPANDED INTO. AND THEY ARE CHILDREN, AND THE CHILDREN THAT WILL COME UP IN SOME OF THE SLIDES TODAY ARE AN AVERAGE AGE OF 28. WE'RE TALKING ABOUT CHILDREN WHO HAVE HAD EXPERIENCE WITH ALCOHOL. THE STUDY BASICALLY FALLS INTO A SERIES OF STEPS, AND THOSE STEPS AGAIN ARE THE BASIS OF THE PRESENTATION. IN 1978, WE HAD A HYPOTHESIS THAT IN ADDITION TO OTHER VERY IMPORTANT CHARACTERISTICS SUCH AS IMPULSIVITY AS WELL AS A PERSONAL HISTORY OF PSYCHIATRIC DISORDERS, WE FOUND THAT A WAY AN INDIVIDUAL RESPONDS WOULD BE A VERY IMPORTANT PREDICTION OF ALCOHOL. SO WE WERE LOOKING AT HOW THE PERSON RESPORDZ TO ALCOHOL OR A LOW LEVEL OF RESPONSE PER DRINK, AND INDEED, THAT FIRST SECTION OF THE STUDY DEMONSTRATED THAT THE LOW LEVEL OF RESPONSE FOR DRINKING IN THESE QUITE YOUNG NON-ALCOHOL USE DISORDERED, NOT BINGE DRINKERS, BUT PEOPLE WHO HAD EXPERIENCE WITH ALCOHOL. AND HOW THAT RELATED, THE LOW RESPONSE RELATED TO A RISK FACTOR FOR ALCOHOLISM. THEN BEGINNING IN 1988, WE HAD COMPLETED OUR ACQUISITION OF THE 453 INDIVIDUAL SUBJECTS. AND NOW WE DID OUR FIRST FOLLOW-UP. AND AT THAT FIRST FOLLOW-UP, DUE TO GOOD CIRCUMSTANCES AND A BIT OF STUBBORNNESS, WE WERE ABLE TO LOCATE 100% OF THE 453, AND ALL BUT THREE AGREED TO THE 10-YEAR FOLLOW-UP. THAT SECTION OF WHAT I'LL TALK ABOUT TODAY IS TO ADDRESS THE QUESTION OF WHETHER THE LOW LEVEL OF RESPONSE, WHICH I'LL EXPLAIN MORE ABOUT IN A BIT, THE LOW LEVEL OF RESPONSE, INDEED IT DID. THEN WHAT WE'RE GOING TO DO IS LOOK AT 1993 TO THE PRESENT, WHERE WE ARE SEARCHING FOR GENES ALL WITH VERY SKILLED COLLABORATORS, AS WELL AS ENVIRONMENTAL CHARACTERISTICS THAT IMPACT AND SOME OF THEM IMMEDIATE HOW THE LOW RESPONSE TO DUBTS OR PROBANDS, AND THEIR DRINKING OFFSPRING, HOW THOSE MEDIATORS WORK, AND THOSE GENES WORK. AND I'M GOING TO PUT A SPECIAL EMPHASIS AT THE CLOSE OF THIS TALK TODAY ON A GROUP OF STUDIES WE'VE DONE IN THE LAST FIVE YEARS, ESPECIALLY WITH WORK ACROSS GENERATIONS. SO LET LOOK NOW FIRST AT THE BACKGROUND FOR THIS SERIES OF STUDIES, AS BASICALLY WE LOOKED AT THINGS IN 1978, AND AGAIN, THE ABBREVIATION SDPS IS SAN DIEGO PROSPECTIVE STUDY. THE BASE STUDY THAT I'LL BE REFERRING TO TODAY. AS I STARTED TO GET INTO THIS KIND OF WORK IN THE MID 60s IN MEDICAL SCHOOL AND THEN AS A RESIDENT AND THEN AS A FACULTY MEMBER IN THE 70s, IT BECAME PRETTY OBVIOUS THAT THERE WERE STRONG GENETIC IMPACTS ON ALCOHOLISM BUT THAT ALCOHOLISM OR BETTER SAID ALCOHOL USE DISORDERS ARE INDEED VERY HETEROGENEOUS RESPONDING TO BOTH GENES AND ENVIRONMENT INTERACTION. SO THE SEARCH THEN TURNED TO MULTIPLE CHARACTERISTICS, WHICH IS GOING TO BE THE NEXT SLIDE, THAT ARE IMPACTING ON THE ALCOHOL USE DISORDER, HEAVY DRINKING AND ALCOHOL PROBLEMS, AND EACH OF THOSE CHARACTERISTICS THAT PEOPLE HAVE LOOKED AT OVER THE YEARS ARE LIKELY TO ALSO RELATE TO BOTH GENES AND ENVIRONMENT, ROUGHLY 50/50 GENES AND ENVIRONMENT, ALTHOUGH THE SPECIFIC STUDY I WAS REFERRING TO HERE WAS 60/40. WHAT WERE THOSE RISK FACTORS? ALCOHOL METABOLIZING ENZYMES IMPACTING ON HOW A PERSON RESPONDS TO ALCOHOL WERE DISCOVERED IN AT LEAST THE 1960s, AND OF COURSE THOSE ENZYMES ARE -- TO CONTROL FOR SOMETHING THAT BY THE MID 1970s WAS TO MY IMPRESSION ALREADY WELL ESTABLISHED. THE NEXT CHARACTERISTIC THAT I CONSIDERED IN THE MID 70s IS WHETHER A PERSON MAKES DECISIONS WITHOUT THINKING OF THE CONSEQUENCES, AND HE OR SHE IS ON THE EXTREME OF THAT. HIGHER LEVELS OF IMPULSIVITY AND PROBABLY GOING BACK TO THE 1930s, THERE WERE STUDIES THAT HIGHER LEVELS OF IMPULSIVITY IS RELATED TO PROBLEMS WITH BOTH ALCOHOL AND DRUGS. THEN PSYCHIATRIC DISORDERS, AS GEORGE KOOB REFERS TO THE DARK SIDE OF SUBSTANCE USE DISORDERS, AND THOSE PSYCHIATRIC DISORDERS AS WELL AS OTHERS ALSO IMPACT ON THE RISK FOR ALCOHOL USE DISORDER, BUT I WAS AGAIN FORTUNATE ENOUGH TO HAVE GOOD ADVICE TO TRY TO FOCUS ON SOMETHING THAT WAS A BIT DIFFERENT, THE LOW SENSITIVITY TO ALCOHOL, WHICH IS AGAIN BASICALLY GOING TO BE DESCRIBED FOR YOU THE NEXT SERIES OF SLIDES. HERE BY WAY OF BACKGROUND ARE SOME STATEMENTS AND THIS DEVELOPED OVER THE YEARS, AND THEY DEMONSTRATE WHY WE HYPOTHESIZE THAT THE LOW SENSITIVITY TO ALCOHOL WOULD BE ONE OF MANY CHARACTERISTICS INCLUDING HIGH SENSITIVITY IN SOME INDIVIDUALS, THAT IS -- AND MORE AND MORE -- MORE LEVELS OF EXCITEMENT WHEN DRINKING, AS WELL AS CARDIAC CHANGES BUT THE LOW SENSITIVITY BY ITSELF WOULD HELP EXPLAIN WHY, WHEN ESPECIALLY YOUNG PEOPLE BEGIN THEIR DRINKING PATTERNS, THEY ARE DRINKING FOR EFFECTS, LIKE INTOXICATION, AND IT TAKES MORE ALCOHOL TO HAVE THOSE EFFECTS, THEY'RE GOING TO DRINK MORE PER OCCASION, AND THEN THERE ARE THOSE THAT RELATE TO ASSOCIATING WITH HEAVIER DRINKING PEERS, EXPECTATIONS IS WHEN THEY DRINK A LOT USING ALCOHOL TO COPE WITH STRESS AND OTHER CHARACTERISTICS, THAT IN A NUTSHELL IS THE RATIONALE FOR THE LOW SENSITIVITY TO ALCOHOL AND ITS RELATIONSHIP TO ALCOHOL PROBLEMS. WHEN WE BEGAN THIS STUDY IN 19 -- ACTUALLY 75, WE DID THE PILOT STUDY, BUT IN 1978, WITH THE DATA THAT YOU'LL BE SEEING ME RETRUE TODAY. WHEN WE BEGAN THIS STUDY, WE SELECTED PEOPLE WHO WERE AT HIGH RISK FOR ALCOHOL USE DISORDERS. IN THIS EXAMPLE, THEY HAVE AN ALCOHOL USE DISORDER PARENT, AND PEOPLE WHO ARE AT LOW RISK FOR ALCOHOL USE DISORDER, INDIVIDUALS WHO ARE FAMILY HISTORY NEGATIVE, AND WE MATCH THEM ON THINGS THAT WOULD BE LAKELY TO IMENT PACT THEIR REACTION TO COMOM AS WELL AS MATCH THEM ON THINGS THAT MIGHT IMPACT ON THEIR BLOOD-ALCOHOL LEVEL OVER TIME IN AN . ON THE LEFT SIDE, YOU SEE THE BLOOD ALCOHOL OR IT COULD BE BREATH ALCOHOL MEASURE, AND YOU'LL NOTICE THAT IN THIS GROUP, ONCE YOU GET TO ABOUT 15 OR 20 PAIRS OF PEOPLE MATCHED ON PERCENT BODY WATER, USUAL DRINKING, SMOKING AND USUAL CANNABIS USE, YOU CAN END UP WITH GRAWPS THAT, GROUPS THAT AFTER AN OR AL ALCOHOL CHALLENGE ARE BASICALLY IDENTICAL IN THEIR BLOOD-ALCOHOL LEVEL OVER TIME, BUT DIFFER DRAMATICALLY AS A GROUP, NOT EVERY INDIVIDUAL, ON THE INTENSITY OF RESPONSE TO ALCOHOL, THE GREEN LINE, FOR INDIVIDUALS WHO HAVE A POSITIVE FAMILY HISTORY. AND AMONG THE EFFECT, WHICH IN THIS CARTOON ARE LISTED ON THE SIDE OF THE SLIDE, ARE SUBJECTIVE FEELINGS OF INTOXICATION OVERALL LOWER IN THESE YOUNG DRINKERS WITH FAMILY HISTORIES. BODY SWAY WHICH IS A MODE OF PERFORMANCE TEST, SEVERAL EEG MEASURES AND HORMONES, INCLUDING THE CHANGES WITH WITH ALCOHOL WITH PRO ACTIN, CORTISOL AND ACTH. SO WHEN WE BEGAN THE WORK, ALL OF OUR STUDIES WERE BASICALLY BASED ON THE LEVEL OF RESPONSE TO ALCOHOL AS MEASURED BY AN ALCOHOL CHALLENGE. NOW MOST IF NOT ALL STUDIES HAVE REPLICATED THIS WORK IF THEY SELECT AND MATCH SUBJECTS THE WAY WE'RE TALKING ABOUT, BUT THERE'S VARIABILITY OF COURSE. AND SOME STUDIES DON'T SHOW THIS, BUT THIS IS AN AGE-OLD PATTERN. NOW WE FACE A PROBLEM. WE HAVE SOMETHING RUNNING IN FAMILIES, THIS LOW RESPONSE AT A GIVEN BLOOD-ALCOHOL LEVEL, USUALLY ABOUT .06 AT THE HEIGHT OF THE BLOOD ALCOHOL CURVE, AND IN ORDER FOR -- AND THIS CHARACTERISTIC IS NOT ONLY FA FAMILIAL POTENTIALLY BUT ALSO SERIOUS ALCOHOL PROBLEMS AND SERIOUS HEAVY DRINKING IN THE FUTURE. BUT IT TAKES -- TO DO THESE ALCOHOL CHALLENGES AND WAIT AROUND UNTIL PEOPLE'S BLOOD-ALCOHOL LEVEL ARE BASICALLY ZERO. AND ANYWAY, BECAUSE IT TAKES SO LONG AND THERE ARE SO FEW -- EXCUSE ME, BECAUSE IT TAKES SO LONG AND THERE ARE SO FEW INDIVIDUALS THAT YOU CAN MEASURE, AND YOU NEED GENETIC ANALYSES OF WE DEVELOPED A SECOND MEASURE, AND THE SECOND MEASURE IS ASKING AN INDIVIDUAL TO THINK BACK, LET'S TAKE THAT FIRST DATA COLUMN, TO THINK BACK TO THE FIRST FIVE OR 10 TIMES THEY HAD ALCOHOL ON THEIR OWN. AND TELL US THE NUMBER OF STANDARD DRINKS, WHEN THEY THOUGHT WAY BACK TO THEM, STANDARD DRINKS THAT IMPACTED ON THE -- THAT WERE REQUIRED, I SHOULD SAY, THE NUMBER OF STANDARD DRINKS THAT WERE REQUIRED TO FEEL ANY EFFECT AT ALL, TO FEEL DIZZY OR SLURRED SPEECH, IF THEY GOT TO THE POINT THEY WERE STUMBLING, HOW MANY DRINKS DID THAT TAKE, AND WHEN THEY FELL ASLEEP WHEN THEY DIDN'T WANT TO. THAT IS PASSING OUT WITH ALCOHOL. HERE OF COURSE YOU MUST REALIZE THAT THE MORE DRINKS IT TAKES FOR EFFECTS, . TWO MEASURES I WANT YOU TO PAY ATTENTION TO, ONE MEASURE IS FIRST FIVE TIMES, SENSITIVITY AS OPPOSED TO ACQUIRED TOLERANCE. THEN THE TWO OTHER MEASURES, RECENT THREE MONTHS AND PERIOD OF HEAVIEST DRINKING HELP US TO ADD TO THE SENSITIVITY, THE EFFECTS OF THE DEVELOPMENT OF TOLERANCE OVER TIME. SO THOSE ARE OUR MEASURES. AND WHY DO I THINK THAT THE HIGHER NUMBER OF DRINKS REQUIRED FOR EFFECTS OR LOWER LEVEL OF RESPONSE PER DRINK IS LIKELY TO BE SENSITIVITY RATHER THAN ACQUIRED TOLERANCE. THIS IS DATA I WAS FORTUNATE ENOUGH TO BE ABLE TO JOIN IN ON FROM THE AVON LONGITUDINAL STUDY OF PARENTS AND CHILDREN, WHICH IS IN RECENT YEARS HAS BEEN SUPPORTED BY THE NATIONAL ALCOHOL INSTITUTE. AND THESE WERE ABOUT 300 KIDS OUT OF ABOUT 3,000, WHO HAD EXPOSURE TO ALCOHOL ENOUGH TO FILL OUT THIS S RE. AND AGAIN, THE HIGHER THE NUMBER OF DRINKS ON THE SRE, THE LOWER THE INTENSITY OF RESPONSE IF YOU WERE TO TEST THEM WITH ALCOHOL. IF WE LOOKED AT THOSE 300 OR SO AT AGE 12, THE AMOUNT THEY DRANK PER OCCASION CORRELATED AT ALMOST .5 WITH THEIR SRE SCORE. AND PROBLEMS AS WELL BUT NOT AS STRONG, ALCOHOL FREQUENCY DIDN'T CORRELATE VERY MUCH AT ALL, BUT MOST OF THESE KIDS HAD CONSUMED ALCOHOL, HAD PERIODS OF DRINKING ALCOHOL, EVENINGS OF DRINKING ALCOHOL LESS THAN FIVE TIMES. THIS COULD BE -- IT IS LIKELY THAT WHEN MEASURED AT LEAST FOR THE FIRST FIVE TO 10 TIMES THAT A PERSON DRANK, THAT IT IS AT LEAST TOUCHING ON SENSITIVITY. SO THAT'S THE 1978 TO 1988 GETTING THE INFORMATION ON WHETHER THE LEVEL OF RESPONSE RELATED TO RISK FACTORS. OTHERS HAVE LOOKED AT NATIVE NATIVE AMERICANS, OTHERS LOOKED AT GROUPS WITH LOW RESPONSE TO ALCOHOL, SUCH AS SARAH PETERSON, AND SHE'S LOOKING AT AFRICAN AMERICANS, AND AMERISTELA MONCHERO, AFRICAN AMERICANS AND JEWS WERE A LITTLE MORE SENSITIVE TO ALCOHOL AND THOSE GROUPS HAVE LOWER LEVELS OF RESPONSE TO -- THEY'RE MORE SENSITIVE TO ALCOHOL THAN A LESSER CHANCE OF DEVELOPING ALCOHOL PROBLEMS. SO 1988, WE START FOLLOWING PEOPLE UP. FIRST FOLLOW-UP FROM A STUDY, 100% OF THE SUBJECTS, AND WHAT WE FOUND, AND I'LL SHOW YOU VERY BRIEFLY, IS THAT THE LOW LEVEL OF RESPONSE TO ALCOHOL PREDICTS EVERY DRINKING AND ALCOHOL USE PROBLEMS LATER IN LIFE. EVEN IF YOU CONTROL FOR DRINKING PATTERNS AT THE TIME WE ORIGINALLY TESTED THEM. AND THAT INFORMATION SERVED AS THE BASIS FOR THE LAST SECTION THAT I'LL SL TODAY, WHICH HAVE TODAY WHIC H WILL INCLUDE INFORMATION ON IF YOU KNOW MORE ABOUT THE ENVIRONMENTAL MEDIATORS OF HOW THE LEVEL OF RESPONSE TO ALCOHOL RELATES TO ALCOHOL OUTCOMES OF AN ADVERSE NATURE, THEN YOU MIGHT BE ABLE TO PUT TOGETHER A PREVENTION STUDY THAT ACTUALLY HELPS YOU TO IDENTIFY PEOPLE WHO ARE AT HIGH RISK AND HELP THEM TO MODERATE THEIR DRINKING PROCLIVITY TOWARD PROBLEMS. SO THE LOW LEVEL OF RESPONSE TO ALCOHOL HAS PREDICTED FUTURE ALCOHOL PROBLEMS IN THE SAN SAN DIEGO PERSPECTIVE STUDY. WE ALSO HAD AN NIAAA STUDY, A SEPARATE STUDY WHERE WE WERE LOOKING AT FMRI OR BRAIN IMAGING CHARACTERISTICS ASSOCIATED WITH A LOW RESPONSE TO ALCOHOL. WE HAD SEPARATE FUNDING FROM THE NATIONAL ALCOHOL INSTITUTE FOR A PREVENTION STUDY I'M GOING TO GET TO IN THE NEXT SECTION. AND THEN WE HAVE STUDIED THE LOW SENSITIVITY TO ALCOHOL USING THE SELF-REPORT RETROSPECTIVE MEASURE, THE SRE AND THE COLLABORATIVE STUDY ON THE GENETICS OF ALCOHOLISM, THE AVON LONGIT STUDY PARENTS & CHILDREN AND THERE ARE ALSO DATA FROM COHORTS IN AUSTRALIA AND IN DENMARK. REMEMBER, NOT ALL STUDIES ARE GOING TO SHOW THE SAME THINGS THAT WE HAVE. MOST STUDIES, HOWEVER, USING THE APPROACHES TO WHAT IT IS THAT WE HAVE BEEN USING SUPPORT OUR FINDINGS. SO LOW RESPONSE GENETICALLY AT LEAST RUNS IN VALLEYS AND IS CHARACTERISTIC OF A VARIETY OF RISK FACTORS RELATED TO ALCOHOL. AND IT PREDICTS HEAVY DRINKING. NOW LET'S TURN TO THE PERIOD FROM 1993 TO THE PRESENT, AND THE ASTERISK INCLUDES INFORMATION THAT HAS BEEN PUBLISHED SINCE 2016. SO WITHIN THE LAST FIVE YEARS OR SO. AND IN THIS PERIOD, WE HAVE SEARCHED FOR GENES RELATED TO THE LEVEL OF RESPONSE TO ALCOHOL, ENVIRONMENTAL CHARACTERISTICS RELATED TO THE LEVEL OF RESPONSE TO ALCOHOL, AND AS YOU'LL SEE, WE'VE BEEN ABLE TO LOOK AT THOSE IN TWO GENERATIONS OF THE SAN DIEGO PROSPECTIVE STUDY. WE BEGAN, REMEMBER, THE SAN DIEGO PROSPECTIVE STUDY IN 1978, THEY WERE 20ISH YEARS OLD. THESE SUBJECTS ARE NOW AN AVERAGE OF ABOUT 55 YEARS OLD. AND OF COURSE THEY WERE LIKELY TO HAVE CHILDREN, AND THE CHILDREN ENTERED OUR STUDY, BOTH THE SONS AND DAUGHTERS, AND WHEN THE KIDS BECAME LIKELY TO BE IN AN INITIATION TO ALCOHOL PERIOD OR SOON THEREAFTER, WE WERE ABLE TO STUDY THEM AS WELL. SO THERE ARE MEASURES WE HAVE ACROSS BOTH GENERATIONS. YES, WITH THE HELP OF PEOPLE AND MANY OTHERS, WE'VE BEEN ABLE TO LOOK FOR POTENTIAL GENE VARIATIONS RELATED TO THE LOW SENSITIVITY TO ALCOHOL. THE STRONGEST. WE KNEW WERE THERE BEFORE WE EVEN STARTED OUR STUDY, AND WE DID OUR BEST TO CONTROL FOR AND THOSE WITH THE ALCOHOL METABOLIZING ENZYMES. JUST BRIEFLY, OUR SAN DIEGO PROSPECTIVE STUDY DO NOT HAVE -- INDIVIDUALS THAT WOULD BE MUCH MORE LIKELY -- THE DEHYDROGENASE 1B MUTATION. AND WE DON'T HAVE JEWS AND BLACKS WHO ARE ALSO VERY LIKELY TO HAVE THOSE GENE VARIATIONS IN ALCOHOL METABOLISM. SO AS BEST WE CAN, WE ARE CONTROLLING FOR THE EFFECT OF THE ALCOHOL METABOLIZING ENZYMES AND LOOKING FOR ADDITIONAL GENES THROUGH ADDITIONAL CHARACTERISTICS THAT ARE LIKELY TO BE CONTRIBUTING TO THE LOW RESPONSE TO ALCOHOL. WE'RE NOT GOING INTO THAT IN VERY MUCH DETAIL. THERE'S THE ARTICLE AS WELL AS AN ARTICLE I DID SEVERAL YEARS AGO IN ALCOHOLISM, CLINICAL AND EXPERIMENTAL RESEARCH, REVIEWING THE INFORMATION ON BOTH THE SRE AND THE ALCOHOL CHALLENGE DEMONSTRATING SPECIFIC GENES. BUT FOR THIS PERIOD, 1993 ON, I'M ALSO EMPHASIZING THE ENVIRONMENTAL AND ATTITUDINAL CHARACTERISTICS, AND AS THEY MIGHT MEDIATE OR PARTIALLY MEDIATE THE LOW RESPONSE TO LATE OR HEAVY DRINKING. WE GET OUR PERSONAL HISTORY FROM THE STRUCTURED INTERVIEW CALLED THE SEMI STRUCTURED ASSESSMENT OF THE GENETICS OF ALCOHOLISM THAT WAS ALCOHOLISM. WE USED A SUBSET OF THE KAROLINSKA OR BARRATT. WE LOOKED AT ORIGINAL SUBJECTS AND THEIR OFFSPRING, WE USED A DRINKING TO COPE SCALE, WE USED A PART OF THE IMPORTANT PEOPLE AND ACTIVITY SCALE FOCUSING ON PEER DRINKING AND THEN WE GET OUR INFORMATION ON LEVEL OF RESPONSE TO ALCOHOL THROUGH ALCOHOL CHALLENGES OR THROUGH THIS SELF-REPORT OF THE EFFECTS OF ALCOHOL RETROSPECTIVE MEASURE. AND LET'S TAKE A LOOK AT A SUMMARY KIND OF CARTOON OF WHAT IT IS WE'VE FOUND IN THE SAN DIEGO PRO PROSPECTIVE STUDY AS WELL AS THE COLLABORATIVE STUDY, WE'VE ALREADY SHOWN YOU THAT THE FAMILY HISTORY OF ALCOHOLISM IS RELATED TO MANY THINGS, BUT IT IS ALSO RELATED TO A LOW LEVEL OF RESPONSE TO ALCOHOL AT LEAST AS MEASURED IN 20-YEAR-OLDS. AND THEN THE LEVEL OF RESPONSE TO ALCOHOL CORRELATES WITH A BUNCH OF THINGS. IF YOU HAVE A LOW RESPONSE PR DRINK AND ARE DRINKING MORE THAN MOST OTHER PEOPLE, THEN YOU TEND TO DEVELOP A PEER GROUP THAT DRINKS AS HEAVILY AS YOU DO. THIS USE IN HEAVY AMOUNTS OF ALCOHOL TO GIVE YOU THE DESIRED EFFECT YOU WANT GIVES YOU AN EXPECTATION THAT YOU NEED TO DRINK A LOT TO HAVE FUN, AND THEN THAT ALLOWS STRESS IN OUR POPULATION, DID NOT HAVE A MAJOR POTENTIAL MEDIATING EFFECT OF THE ROLE OF THE LEVEL OF RESPONSE TO ALCOHOL, STRAIGHT LINE FROM THAT TO HEAVY DRINKING AND ALCOHOL PROBLEMS, IT IS HOW USING ALCOHOL TO COPE RATHER THAN OVERALL COPING -- EXCUSE ME -- OVERALL STRESS LEVELS THAT MATTER. AND THEY'RE ALL CONNECTED. WELL, NOT ALWAYS THE SAME IN EVERY SUBSET, BUT THIS IS THE PATTERN WE USUALLY SEE, AND IF YOU ADD TO THIS PATTERN A STRUCTURAL EQUATION MODEL, AN IMPULSIVITY MEASURE, YOU SEE THE IMPULSIVITY MEASURE ALSO RELATES TO FAMILY HISTORY BUT ONLY RELATES TO LEVEL OF RESPONSE AT ABOUT .10, AND IT FINDS ITS WAY THROUGH THE STRUCTURAL EQUATION MODEL IN A DIFFERENT PATTERN THAN DOES THE LOW LEVEL OF RESPONSE TO ALCOHOL. BUT NOW FOR WHAT FOR ME IS AGAIN THE FINAL SECTION OF THIS PRESENTATION, BUT IT IS THE FUN THAT I HAVE HAD OVER THE LAST FIVE YEARS WITH ACCESS TO A DATASET THAT IS LONGITUDAL, MALES AND FEMALES, AND IS ONGOING ACROSS TWO GENERATIONS. THE FIRST THING THAT I'M GOING TO SHARE WITH YOU ARE SOME RECENT STUDIESS THAT WE'VE PUBLISHED ON THE PRO PROBANDS AND OFFSPRING. HERE WE HAD SOMETHING THAT WAS GREAT FUN. AT THE TIME OF THESE ANALYSES, THERE WERE 216 DRINKING OFFSPRING WHO FILLED OUT THE SRE, AND THEY WERE AN AVERAGE AGE OF 28. WHICH MEANS THAT THEY WERE IN THE GENERAL RANGE OF THE AGE AT WHICH WE STUDIED THEIR ORIGINAL -- THEIR FATHERS, THE PROBANDS FROM THIS STUDY. BUT I'M GOING TO PULL DATA FROM THE BRO BANDS AT AGE 31, ABOUT THEIR 10-YEAR FOLLOW-UP, AND TAKE A LOOK AT HOW THESE LOOK ACROSS PROBANDS AND DRINKING OFFSPRING. WELL, AS THIS PART OF THE SLIDE SHOWS YOU, THE AGE IS SIMILAR BUT NOT IDENTICAL, AND THE FATHERS HAD SIGNIFICANT BUT NOT OVERLY SIGNIFICANT, ABOUT THE .05 LEVEL, HAD A HIGHER NUMBER OF DRINKS ON THE SRE, BECAUSE WE GATHERED THOSE FROM THE PROBANDS AS WELL, THAN THE OFFSPRING. THEY HAD A LITTLE LOWER LEVEL OF RESPONSE PER DRINK, AND THEIR MAXIMUM DRINKS WAS A LITTLE BIT HIGHER. THESE FINDINGS ARE SIGNIFICANT, IT'S NOT A HUGE AMOUNT HIGHER BUT IT'S HIGHER. AND THEN TO MY SURPRISE, THAT THE NUMBER OF THE 11 DSM-IV, DOESN'T CHANGE IF WE LOOK AT DSM-V, THE NUMBER OF THE DSM-IV CRITERIA ENDORSED BY THESE DRINKING PROBABDZ, BANDS, SOME OF WHOM DEVELOPED ALCOHOL USE DISORDERS AND SOME OF WHOM DIDN'T WAS ABOUT 1.6, AND IT WAS HIGHER. THE NUMBER OF ALCOHOL PROBLEMS AND THE PROPORTION OF PEOPLE IN THE OFFSPRING GROUP WHO MET CRITERIA FOR AN ALCOHOL USE DISORDER WAS MUCH HIGHER THRAN IN THE ORIGINAL PROBANDS. GOES TO SHOW YOU WHAT I KNOW. I HAD PREDICTED THAT IN THE OFFSPRING GENERATION, THAT THE IMPACT OF THE LEVEL OF RESPONSE TO ALCOHOL, THAT IS, RELATIONSHIP TO HEAVY DRINKING AND ALCOHOL PROBLEM, WOULD BEGIN TO DIMINISH, THAT WE WERE JUST FORTUNATE ENOUGH TO FIND IT IN ONE GENERATION AND IT WOULD KIND OF BE THERE BUT THAT IT WOULD DIMINISH IN ITS IMPACT AND THAT TURNED OUT NOT TO BE TRUE. WE ALSO COULD ACROSS GENERATIONS LOOK AT THIS SELF-REPORT MEASURE, FIRST FIVE TO 10 TIMES, AND THE TOTAL THAT INCLUDES BOTH POTENTIAL SENSITIVITY AND DEVELOPMENT OF TOLERANCE, AND WE COULD LOOK AT THIS BOTH IN PROBANDS, WHICH IS CORRELATIONS OF .3ISH AND .6 ICIAL .6ISH IN SPOUSES, AND IN ADDITION TO THAT, WE CAN LOOK AT THE SONS AND DAUGHTER, WHICH IS THE RELATIONSHIP BETWEEN SRE5 AND SRET, SRE TOTAL, IN MAXIMUM QUANTITY OF DRINKING WAS ACTUALLY A GOOD DEAL HIGHER IN THE SONS BS,S REGARDING THE SRE-5 AND T AND A LITTLE BIT HIGHER IN THE DAUGHTERS. AGAIN SIGNIFICANT WITH WE COULD TEST AND INDEED THE LOW RESPONSE WAS MORE CLOSELY RELATED TO ALCOHOL USE DISORDERS IN THE NEXT GENERATION OF THAT SAN DIEGO POST STUDY. THEN DOES THE LEVEL OF RESPONSE TO ALCOHOL AS MEASURED BY THIS SELF-REPORT MEASURE, DOES IT CORRELATE ACROSS GENERATIONS. AND THE PROBANDS SRE-5 CORRELATED WITH THE SONS ARE-5, .16 TO .22 BUT DID NOT CORRELATE STRONGLY WITH THE DAUGHTERS' PROBLEM. YOU CAN ONLY LOOK AT LEVEL OF RESPONSE TO ALCOHOL WITHIN EACH SEX, BECAUSE WOMEN AND MEN DIFFER ON HOW QUICKLY THEY METABOLIZE ALCOHOL AS WELL AS THE BLOOD-ALCOHOL LEVEL THEY'RE LIKELY TO GET PER DRINK. AND THE MOTHERS CORRELATE CLOSER WITH THEIR NEXT GENERATION, THEIR DAUGHTERS, THAN THEY DO THEIR SONS. AND AGAIN, ONE OF THE THINGS THAT WE NEVER DREAMED WE WOULD BE ABLE TO GO ON TO BE ABLE TO TEST ACROSS GENERATION. THE BROTHER PAIRS AND SISTER PAIRS CORRELATE VERY WELL. SO WE COULD CORRELATE ACROSS GENERATIONS ABOUT HOW WELL THEY PERFORM AND HOW WELL THEY SCORE THEMSELVES ACROSS GENERATIONS. THE NEXT OF LAST OF THESE EXAMPLES, THERE WILL BE ONE MORE, OF THE KINDS OF THINGS YOU CAN DO WITH A PROSPECTIVE STUDY SUCH AS THIS. AND THE GOOD FORTUNE OF HAVING RELATIVELY CONSISTENT FUNDING OVER TIME IS WE HAD THE OPPORTUNITY OF A SECOND GRANT WE HAD AT THE NATIONAL ALCOHOL INSTITUTE, WE WERE ABLE TO DO A PREVENTION STUDY. BASED ON THAT STRUCTURAL EQUATION MODEL I SHOWED YOU. WE TOOK 500 INCOMING FRESHMEN, AGE 18, WHO WERE DRINKERS. WE ASSESSED THEIR DRINKING AT BASELINE, AND THEY WERE MADE UP EQUALLY OF LOW RESPONDERS AND HIGH RESPONDERS, RELATIVELY INSENSITIVE AND SENSITIVE TO ALCOHOL, AND THAT WAS AFTER MATCHING THEM ON USUAL DRINKING, SMOKING AND MARIJUANA USE. THE INDIVIDUALS IN THE STUDY COULD BECOME CONTROLS WHO GOT NO EDUCATION ON ALCOHOL, OR THEY COULD BE IN ONE OF TWO EDUCATION GROUPS, EACH OF WHICH HAD WATCHED, EACH OF WHICH WATCHED FOUR 45 MINUTE VIDEOS, THEY WATCHED FOUR 45 MINUTE VIDEOS, SOME OF WHICH PUT A BIGGER EMPHASIS ON LEVEL OF RESPONSE, LOW LEVEL OF RESPONSE, SOME OF WHICH JUST GAVE A GENERAL OVERVIEW INCLUDING LEVEL OF RESPONSE, BUT THE INFORMATION GIVEN WAS BASICALLY THE SAME. I KNOW BECAUSE I PUT THE FOUR VIDEOTAPES TOGETHER FOR THE LEVEL OF RESPONSE-BASED GROUP AND FOR THE STATE OF THE ART MEANING GENERIC INFORMATION, INFORMATION WAS THERE, IN BOTH, BUT THE EMPHASIS WAS DIFFERENT. AND THEN WE FOLLOWED THESE INDIVIDUALS UP AND CONTINUED TO HAVE 93% THAT DID AT LEAST THREE OF THE FOUR VIDEOS AND AT LEAST FIVE OF THE SEVEN FOLLOW-UP PERIODS. AND IF WE TAKE A LOOK, CARTOON, THE DATA ARE MORE COMPLICATED, BUT IF WE TAKE A LOOK AT OVER 55 WEEKS AT THE BOTTOM OF YOUR SLIDE, AND LOOKED AT THE MAXIMUM QUANTITY CONSUMED, THIS IS WHAT HAPPENED TO THE CONTROL LOW RESPONDERS. IT WAS A PRETTY CONSISTENT INCREASE OVER TIME THAT BIG PEAK YOU SEE UP THERE IS A DRINKING FESTIVAL. IT'S NOT MEANT TO BE A DRINKING FESTIVAL BUT IT'S A WEEK OF CELEBRATION OF SOMETHING CALLED THE SUN GOD FESTIVAL, AND BOY, DID THOSE PEOPLE START TO PEAK ON THEIR MAXIMUM DRINKS DURING THAT PERIOD, WHICH WAS WHERE ONE OF OUR MEASURES WAS. SO HERE'S WHAT HAPPENED OVER TIME TO THE PEOPLE WHO WERE LOW RESPONDERS BUT GOT THE GENERAL INFORMATION. IT WAS A SIGNIFICANT DECREASE, AND IF THE LOW RESPONDERSS WERE ASSIGNED TO THE GROUP THAT REALLY EMPHASIZED LOW RESPONSE, THEIR DECREASED MAXIMUM DRINK OVER TIME WAS THE STRONGEST OF ALL. AND FOR THE HIGH RESPONDERS, THEY DIDN'T NEED ANYTHING, THEY REALLY DIDN'T CHANGE MUCH OVER TIME BUT THE LOW RESPONDERS CERTAINLY DID. NOW, THE VERY LAST OF THE THINGS THAT I'M GOING TO TALK ABOUT IS JUST VERY QUICKLY. IT IS TWO PAPERS THAT WE'VE HAD VERY RECENTLY, ONE STILL IN PRESS AND THE OTHER JUST RECENTLY PUBLISHED. THE FIRST WAS BASED ON THE FACT THAT IN OUR INTERVIEWS, WE REVIEW THE NUMBER OF ALCOHOL PROBLEMS AND DRINKING PATTERN FOR ANYONE ON THE PROBANDS OR DRINKING OFFSPRING. THEN AT THE VERY END OF THAT ALCOHOL SECTION, AFTER THEY REPORTED WHATEVER THEY'RE REPORTING, WE ASKED HOW WOULD YOU RATE YOURSELF IN GENERAL, ARE YOU AN ABSTAINER, A MODERATE SOCIAL DRINKER, A PROBLEM DRINKER, AN ALCOHOLIC? AND 67% OF THE PROBANDS AND 82% OF THOSE KIDS AFTER REPORTING ENOUGH PROBLEMS TO BE DIAGNOSED WITH AN ALCOHOL ABUSE DISORDER, WE STUCK TO DMS4 FOR THAT DISTINCTION, 67% AND 82% CALLED THEMSELVES MODERATE SOCIAL DRINKERS. AND THE ONLY IMPORTANT THING HERE IS, THIS GIVES US THE OPPORTUNITY WITHIN TWO AGE GROUPS TO IDENTIFY THE DSM CRITERIA THAT THEY WERE MOST LIKELY TO IGNORE. AND EVEN THOUGH THEY HAD ALCOHOL PROBLEMS, NOT ADMIT TO ALCOHOL PROBLEMS IN THOSE AREAS, AND THAT WAS MOSTLY RELATED TO WHETHER THEY SAW THEMSELVES AS A NON-ALCOHOL USE DISORDER INDIVIDUAL OR NOT. THE OTHER IS THAT IN MY KIND OF STUDIES, IN MINE THAT BEGAN IN 1978, WE DIDN'T GO OUT AND INTERVIEW ALL THE RELATIVES TO BEGIN WITH. WE TOOK THE OFFSPRINGS' REPORT ABOUT THEIR PARENTS, AND INDEED, NOW WE FOLLOWED UP THE SECOND GENERATION AND WE GOT THE FIRST GENERATION, THE PROBAND, OVER TIME, AND ALMOST 80% OF THE OFFSPRING DID NOT KNOW THAT THEIR FATHERS WERE HAVING ANY TROUBLES WITH ALCOHOL. AND IT WAS THE CHARACTERISTICS OF THE FATHERS, THOSE STARS ARE INFORMATION THAT ENDED UP BEING A SIGNIFICANT CONTRIBUTOR TO A REGRESSION ANALYSIS. THAT IT WAS MOSTLY IN YELLOW AND ESPECIALLY THE ONES WITH STARS, THE CHARACTERISTICS OF THE FATHER AND NOT THE CHARACTERISTICS OF THE OFFSPRING THAT PREDICTED WHETHER THE KID DID NOT KNOW OR AT LEAST DID NOT ADMIT ABOUT KNOWING THAT HIS OR HER FATHER WAS HAVING ALCOHOL PROBLEMS. THIS ALLOWS ONE TO BE ABLE TO BEGIN TO INTERPRET BETTER THE CHARACTERISTICS OF INDIVIDUALS MORE LIKELY TO UNDERREPORT IN A FAMILY HISTORY STUDY. BY THE WAY, OUR FAMILY HISTORY STUDY TURNS OUT THAT OF COURSE AMONG THE PEOPLE WHEN THE KIDS SAY THAT THE PARENT HAS AN ALCOHOL PROBLEM, ALMOST 100% OF THE TIME THE PARENT DOES. AND THAT ALLOWS YOU TO AT LEAST DO AN INTENSIVE STUDY SUCH AS WE HAVE, OF A SUBSET. NOT EVERYBODY, BUT A IS UPSET IS SUBSET O F INDIVIDUALS WHO ARE BEING IDENTIFIED IN A FAMILY HISTORY STUDY. I WANT TO THANK YOU FOR GIVING ME THE OPPORTUNITY TO SHARE THESE DATA WITH YOU AND THEN EXPRESSMYCIN SEER THANKS TO THE NATIONAL ALCOHOL INSTITUTE FOR ALL OF THE HELP BOTH DIRECTLY FUNDED AS WELL AS BY IMPACTS THAT THE VARIOUS PEOPLE HAVE HAD ON THE WORK THAT WE'RE DOING. AND SO THE CONCLUSIONS I'D LIKE TO LEAVE YOU WITH IS THAT THIS CROSS-GENERATIONAL STUDY INVOLVING BOTH MALES AND FEMALES OVER TIME HAS SOME UNIQUE VALUES TO IT. IT'S NOT THE ONLY WAY TO DO THE WORK BUT IT HAS SOME UNIQUE CHARACTERISTICS ABOUT IT THAT ALLOW US TO ADDRESS QUESTIONS THAT MOST OTHER -- THESE ALLOW US TO ADDRESS QUESTIONS THAT MOST OTHER STUDIES CAN'T EVEN BEGIN TO LOOK AT. BECAUSE WE HAVE THE -- BECAUSE WE HAVE INDIVIDUALS IN TWO SUCCESSIVE GENERATIONS OF THESE FAMILIES. THESE ARE CHALLENGING TO CARRY OUT. ANY LONGITUDINAL STUDY IS CHALLENGING TO KEEP GOING, BUT WE HAVE BEEN ABLE TO DO THAT. THESE STUDIES, SUCH AS LEADING TO THE PREVENTION STUDY AS WELL AS THE DENIAL STUDY, AND TRYING TO UNDERSTAND MORE ABOUT WHO DOES AND DOESN'T CORRECTLY IDENTIFY ALCOHOL USE DISORDERS IN THEIR PRIOR GENERATION, ALLOWED US TO ADDRESS THOSE COMPLEX ISSUES. THIS STUDY AGAIN COULD NOT BE DONE WITHOUT THE HELP OF MY FRIENDS AND COLLEAGUES AT THE NIAAA, AS WELL AS MY FRIENDS AND COLLEAGUES IN THE COLLABORATIVE STUDY ON GENETICS OF ALCOHOLISM, AND THE AVON LONGITUDINAL STUDIES ON PARENTS AND CHILDREN. AND IF YOU HAD TALKED TO ME IN 1978, I WOULD HAVE NEVER DREAMED THAT I WOULD HAVE HAD THE OPPORTUNITY TO HAVE SUCH FUN AND HOPEFULLY ADD SOMETHING USEFUL TO THE LITERATURE AS I AM STILL HAVING AND HAVE HAD FOR 35 YEARS. SO WITH THAT, I'LL CLOSE MY TALK, AND I'M LOOKING FORWARD TO QUESTIONS THAT PEOPLE MIGHT ASK. >> SO, EVERYONE, WE'RE NOW IN THE QUESTION AND ANSWER SESSION, AND PLEASE FOLLOW THE INSTRUCTIONS ON THE SCREEN TO SUBMIT YOUR QUESTIONS TO DR. SCHUCKIT. WE ALREADY HAVE A GOOD HERD OF QUESTIONS HERE FOR YOU, MARC. AND I'M GOING TO ASK YOU SO WE CAN COVER ALL THE QUESTIONS WHETHER YOU CAN ADDRESS THEM IN A TIMELY MANNER. SO LET ME GET TO THE FIRST ONE HERE. THE QUESTION IS I WORK IN -- THIS IS FROM MARILYN IN ALASKA CENTER. I WORK IN THE FIELD OF FETAL ALCOHOL SPECTRUM DISORDERS. I'M STRUCK BY THE COMMENTS ABOUT IMPULSIVITY, WHICH IS MUCH MORE COMMON IN INDIVIDUALS WITH FETAL ALCOHOL SPECTRUM DISORDER. I'M WONDERING IF CONSIDERATION HAS BEEN GIVEN OR FUTURE WORK MIGHT BE DONE TO ASCERTAIN WHETHER ANY OF YOUR COHORT GROUP MEMBERS EXPERIENCE PRENATAL ALCOHOL EXPOSURE. BY WAY, MARC, I FORGOT TO SAY, THAT WAS A WONDERFUL TALK. FANTASTIC, TAKING US THROUGH EXACTLY HOW YOU DEVELOPED THE COHORTS AND ALL THE WONDERFUL ANSWERS TO QUESTIONS THAT WE'VE LONG HAD THAT HAVE BEEN ANSWERED BY THE COHORTS. SO THE QUESTION IS ABOUT IMPULSIVITY AND PRENATAL ALCOHOL EXPOSURE. DO YOU HAVE ANY INFORMATION ABOUT THOSE TWO AREAS? IS MARC ON YET? >> IN THE PROBANDS FROM THE SAN DIEGO PROSPECTIVE STUDY, THE ALCOHOLIC RELATIVE WAS THE FATHER. WE DID NOT INCLUDE ANYONE WHEN WE STARTED THE STUDY IN 78, WHO HAD A MOTHER WITH AN ALCOHOL USE DISORDER. OF COURSE SOME COULD HAVE -- SO THAT FIRST GENERATION -- THAT IMPORTANT QUESTION. IN THE SECOND GENERATION, OF COURSE, THE OFFSPRING -- STUDY BECAUSE -- THE KIDS, WHERE THE MOTHER WOULD BE A HEAVIER DRINKER. OUR SAMPLE WOULD NOT BE IDEAL TO LOOK AT THIS IMPORTANT QUESTION BECAUSE BY THE NATURE OF GOING ACROSS TWO GENERATIONS AND STUDYING PEOPLE SO INTENSIVELY OVER TIME, THE SAMPLE WOULD BE RELATIVELY SMALL, AND I DOUBT WE COULD ADD SOMETHING REGARDING FEMALE OFFSPRING WITH ALCOHOL USE DISORDERS AND THE IMPULSIVITY AND THE PROBLEMS RELATED TO THE FETAL ALCOHOL EFFECT. I DON'T THINK WE CAN ADD SOMETHING IMPORTANT TO LITERATURE, BUT THE NATIONAL ALCOHOL INSTITUTE HAS SOME SUPERB DATA, AS DO OTHER PEOPLE THROUGH OTHER FUNDING SOURCES, BUT PRIMARILY THROUGH THE NIAAA, SOME FANTASTIC STUDIES OF EXACTLY WHAT YOU OBSERVED, WHICH IS THAT PART OF THE FETAL ALCOHOL SYNDROME IS IMPULSIVITY, AND BY THE WAY, THERE IS A WONDERFUL SERIES OF BOOKS THAT TALK ABOUT RAISING CHILDREN WITH FETAL ALCOHOL SYNDROMES, BUT INDEED YOUR OBSERVATION IS CORRECT, IT'S NOT SOMETHING THAT OUR STUDY ADDS A GREAT DEAL TO. >> AND MARC, FROM GRAHAM MASON AT YALE, COULD SOME OF THE ACCELERATION OF DRINKING ACROSS GENERATION ARISE FROM THE OVERALL HEAVIER DRINKING ACROSS THE U.S. POPULATION? THAT IS, IF THE CHILDREN COULD BE LIVING IN THE TIME OF THEIR PARENTS, PERHAPS THEY WOULD BE DRINKING SIMILAR AMOUNTS. >> GRAHAM, THANK YOU. I AGREE THAT THAT'S ONE OF THE LOGICAL EXPLANATIONS, THAT IF WE TAKE A LOOK VERY BRIEFLY AT WHAT IS IT THAT IMPACTS ON HEAVIER DRINKING, BINGE DRINKING AND ALCOHOL-RELATED PROBLEMS, AS WE LOOK AT THAT, AS WE LEARN FROM KATHERINE, ONE OF THE THINGS, OF COURSE, IS GOING TO BE CONTEXT IN WHICH THE DRINKING OCCURS AND THE ATTITUDES TOWARDS ALCOHOL, AND THE -- I'LL BET THAT ONE OF THE CONTRIBUTORS TO THE HIGHER RATE OF ALCOHOL USE DISORDERS AND CLOSER RELATIONSHIP OF THE LOW LEVEL OF RESPONSE TO ALCOHOL TO ALCOHOL USE DISORDERS IN THAT SECOND GENERATION RELATES TO A COHORT EFFECT THAT IS IMPACTING ON WHAT IS ACCEPTABLE LEVELS OF DRINKING. AND WHAT IS IT ONE SHOULD BE SEEKING OUT DURING A DRINKING SESSION. GEORGE, CAN'T HEAR YOU. I COULDN'T HEAR YOU, GEORGE. >> SORRY, IT KEEPS MUTING ME. OKAY. SO I'M GOING TO DENY THAT IT WAS MY FAULT. MICHAEL CHARNESS: GREAT PRESENTATION, WONDERFUL WORK. PRENATAL ALCOHOL EXPOSURE INCREASES THE RISK OF AUD, IN THE CROSS GENERATIONAL STUDY, DID INCREASED RISK CORRELATE DURING PRENATAL EXPOSURE DURING PROBANDS -- DIFFERENT TAKE ON THE FIRST QUESTION. >> I THINK I MAY -- FETAL ALCOHOL SYNDROME AND ATTENTION DEFICIT DISORDER, ESPECIALLY IN THE CONTEXT OF CONDUCT DISORDER SYMPTOMS, ARE INDEED AMONG THE CHARACTERISTICS THAT PREDICT HEAVY ALCOHOL AND DRUG USE. BUT IN OUR FIRST GENERATION, OF COURSE, THAT'S NOT SOMETHING THAT WE WOULD HAVE BEEN ENRICHED FOR. AND IN THE SECOND GENERATION, OUR POPULATION WOULD HAVE BEEN A BIT TOO SMALL WITH HEAVY DRINKING MOTHERS TO BE ABLE TO HAVE ADDRESSED THAT ISSUE. >> OKAY. WE'VE GOT A HERD OF QUESTIONS HERE. I'M WORKING MY WAY BACKWARDS. DEB, IF YOU COULD JUST HOLD FOR A SECOND SO I CAN GET CAUGHT UP. QUESTION, I AM A PROGRAM DEVELOPER FOR CELEBRATING FAMILIES, WHICH WORKS WITH IDENTIFIED FAMILIES OF AUD AND SUBSTANCE USE DISORDER. WHICH OF THESE STUDIES SHOULD WE BE FOCUSING ON? WE WOULD BE VERY OPEN TO A STUDY, PROGRAM IS NATIONALLY DISTRIBUTED BY NACOA. >> IF I UNDERSTAND THE QUESTION CORRECTLY, PROBABLY THE MAJOR IMPACT OF ANY OF THE WORK THAT I'VE DONE IN THE LAST OR I SHOULD SAY MY GROUP, IT'S NOT JUST ME, HAVE DONE IN THE LAST FIVE YEARS OR SO, IS THAT PREVENTION TRIAL. THAT IF YOU CAN IDENTIFY A CHARACTERISTIC ASSOCIATED WITH INCREASED RISK FOR ALCOHOL OR DRUG USE DISORDERS, AND A LEVEL OF RESPONSE TO ALCOHOL, LOW LEVEL OF RESPONSE IS RELATED ONLY TO ALCOHOL USE DISORDER RISK, AND IF YOU CAN IDENTIFY THE MEDIATORS OF WHICH THERE MUST BE MANY, BUT WE ONLY STUDIED MORE INTENSIVELY FOUR OR FIVE. IF YOU CAN IDENTIFY SOME OF THE MEDIATORS THAT MAGNIFY THE EFFECT OF THE LOW RESPONSE TO ALCOHOL IN OUR INSTANCE BUT IT COULD BE A SEPARATE STUDY DONE WITH IMPULSIVITY. SUCH AS DONE BY PATRICIA KONROD IN THE U.K. AS WELL AS CANADA. YOU CAN TAKE INDIVIDUALS WITH A PREDISPOSITION, THAT IS MEDIATED BY A RANGE OF MEDIATORS, AND TEACH THEM HOW TO CHANGE SOME OF THE MEDIATORS. AND WHEN YOU DO THAT, LIKE TEACHING THEM TO RESIST THE IMPACT OF HEAVY DRINKING FRIENDS OR TEACHING THEM TO FIND ADDITIONAL WAYS OTHER THAN ALCOHOL TO DEAL WITH STRESS, YOU DO HAVE A SIGNIFICANT IMPACT, AT LEAST OVER THE NEXT SIX MONTHS, AND PROBABLY THE NEXT YEAR. YOU HAVE A SIGNIFICANT IMPACT ON THEIR RISK FOR PROBLEMS. >> THANK YOU AGAIN. ALLAN WAR 10BURG, ADVERSE CHILDHOOD EXPERIENCES IN THESE FAMILIES AND WHETHER THERE WAS A CORRELATION WITH THE DEVELOPMENT OF AUD OR ANY SPECIFIC GENETIC FACTORS? >> WONDERFUL QUESTION. THAT WHEN YOU PUT A STUDY TOGETHER SUCH AS THIS, YOU CAN'T STUDY EVERYTHING YOU'D LOVE TO STUDY, AND I AGREE THAT ADVERSE FAMILY ENVIRONMENT AND ADVERSE EFFECTS EARLY IN LIFE ARE INCREDIBLY IMPORTANT IN HOW PEOPLE HANDLE STRESS, DEPRESSIVE SYNDROMES, AS WELL AS ALCOHOL AND DRUG USE AND PROBLEMS. BUT THAT WAS NOT THE MAJOR EMPHASIS OF OUR STUDY, AND IN FACT, WE BEGAN IN 1978 WITH THE BELIEF THAT THERE WERE NOT ENOUGH STUDIES OF THE AVERAGE DRINKER WITH PROBLEMS IN THE UNITED STATES WHO ARE INDIVIDUALS WHO COME FROM FAIRLY SOLID BLUE COLLAR/WHITE COLLAR, RELATIVELY HIGHLY FUNCTIONAL FAMILIES. SO THE VERY FACT THAT WE SELECTED INDIVIDUALS WHO WERE DOING OKAY IN LIFE AT AGE 20, MOSTLY FROM BLUE COLLAR/WHITE COLLAR FUNCTIONAL FAMILIES, œHAVE INCLUDED, IF WE'D HAVE HAD TIME, ADVERSE LIFE EXPERIENCES EARLY IN LIFE, BECAUSE THEY CERTAINLY OCCUR IN ANY GROUP, BUT THAT THEY WERE NOT POTENTIALLY AS PROMINENT AS ONE MIGHT HAVE BEEN IF ONE STARTED WITH, LET'S SAY, FOR EXAMPLE, A HIGHLY IMPULSIVE POPULATION. BUT IT'S A WONDERFUL QUESTION, AND IT'S JUST UNFORTUNATE THAT ONCE YOU EMPHASIZE X, Y AND Z, YOU MAY NOT HAVE AS MUCH TIME AS YOU'D LIKE WITHIN A PROTOCOL FOR FOLLOW-UP AND EVALUATION TO MEASURE EVERYTHING THAT WAS IMPORTANT. >> HERE'S A FILL SOP PHILOSOPHICAL ONE FROM ONE OF MOO FRIENDS, DOUG RAMSEY, IF AN INDIVIDUAL MAKES ROBUST COMPENSATORY RESPONSES THAT OPPOSE ALCOHOL'S PHARMACOLOGICAL EFFECTS DURING AN INITIAL ALCOHOL EXPOSURE, WOULD THOSE RESPONSES THAT EFFECTIVELY OFFER ALCOHOL'S EFFECT -- ALCOHOL TO APPEAR INITIALLY INSENSITIVE? >> I DON'T UNDERSTAND THE QUESTION, I'M SORRY. THAT -- I'LL RIF ON IT -- >> DON'T RIF TOO LONG BECAUSE WE'RE RUNNING OUT OF TIME, BUT BASICALLY WHAT HE'S ASKING IS, IF THERE'S AN OPPONENT PROCESS TO THE ALCOHOL EFFECT DURING THAT INITIAL EXPOSURE, DOES THAT MAKE -- IS THAT THE UNDERLYING BASIS FOR WHAT LOOKS LIKE A LOW RESPONSE? >> DEFINE FOR ME OPPONENT PROCESS, IF YOU COULD. >> SO YOU KNOW, IT'S KIND OF LIKE AN INHERENT TOLERANCE, WHICH IS WHAT YOU CALL SENSITIVITY. >> OKAY. NOW IF WE'RE GOING TO TALK ABOUT THAT, OF COURSE I CAN'T CONTROL ALL INFORMATION REGARDING ATTITUDES THAT A PERSON HAS, BUT THESE TWO GROUPS WERE AT BASELINE NOT DISSIMILAR, THEIR EXPECTATIONS OF THE EFFECTS OF ALCOHOL, AND THE LOW RESPONSE IS SEEN FOR THINGS THAT ARE NOT UNDER VOLITIONAL CONTROL, SUCH AS THE EFFECT OF ALCOHOL ON B3 LATENCY ON THE PROPORTION OF THE BACKGROUND CORTICAL EEG AND ALPHA RHYTHM, AND IN THE FMRI MEASURES. SO THERE ARE BIOLOGICAL RESPONSES THAT ARE PART OF THIS LOW SENSITIVITY TO ALCOHOL. >> I THINK THAT'S WHAT DOUG IS ASKING, AND WE'RE GOING TO TAKE IT OFFLINE SO WE CAN GET TO SOME OF THE OTHER QUESTIONS AND YOU GUYS CAN CHAT ABOUT THIS THROUGH EMAIL. I'M GOING TO SEE IF I CAN GET TO A COUPLE OTHER QUESTIONS. SUSAN TRINIDAD. HOW SHOULD WE THINK ABOUT CULTURAL DIFFERENCES AND LEARNED RESPONSES TO ALCOHOL OR THE PERFORMANCE OF INTOXICATION? >> YOU CANNOT, THIS MAY RELATE TO THE EARLIER QUESTION AS WELL, YOU CANNOT TOTALLY RULE OUT OR CONTROL FOR, I SHOULD SAY, CULTURAL DIFFERENCES. THERE'S A PROBLEM THERE. SO RATES OF ALCOHOL USE DISORDERS ARE LOWER AMONG AFRICAN AMERICANS AND LOWER AMONG JEWS, CULTURES IN THE UNITED STATES, AND THOSE TWO GROUPS SHOW HIGHER RATES -- THOSE TWO -- AND IN NATIVE AMERICANS, AS WELL AS -- NATIVE AMERICANS SHOW -- CULTURE IS EXTREMELY HARD TO TEASE OUT. >> SO JOSHUA GOWAN SAYS GREAT TALK, FOR THE INTERVENTION STUDY, YOU SHOWED DATA FOR MAXIMUM DRINKS. DID YOU ALSO SEE DIFFERENCES IN AVERAGE DRINKS OR NUMBER OF DRINKING DAYS? DID YOU ALSO VARY BY INTERVENTION AND LEVEL OF RESPONSE, DID THAT ALSO VARY BY INTERVENTION AND LEVEL OF RESPONSE? SO HE WANTS TO KNOW WHETHER YOU DID AVERAGE DRINKS OR NUMBER OF DRINKING DAYS. >> OKAY, WHAT I'M GOING TO SAY IS, THE LOW SENSITIVITY TO ALCOHOL IS GENERALLY UNRELATED TO DRINKING FREQUENCY, BECAUSE IT'S NOT A PERSONALITY CHARACTERISTIC. AND THE ONLY RELATIONSHIP THAT THE LOW LEVEL OF RESPONSE TO ALCOHOL HAS TO DRINKING FREQUENCY OCCURS INDIRECTLY THROUGH HIGH DRINKING QUANTITIES. BUT IN ADDITION TO THE DRINKING QUANTITIES, MAXIMUM, AVERAGE DRINKING QUANTITIES SHOW VERY SIMILAR PATTERN AS WE LOOKED AT THEM OVER TIME, AND RELATED TO THE EDUCATION PROGRAM, AND ALCOHOL-RELATED BLACKOUT ALSO WERE DIMINISHED IN INDIVIDUALS WITH LOW RESPONSE TO ALCOHOL WHO WERE GIVEN THE LOW RESPONSE-BASED EDUCATION PROGRAM. SO YES, WE DID LOOK AT OTHER OUTCOMES. >> SO TWO LAST QUESTIONS FROM ANDREA KING. CAN YOU COMMENT ON YOUR PROSPECTIVE FOR FUTURE DIRECTION AND PREVENTION EFFORTS ESPECIALLY FOR AT RISK ADOLESCENTS AND EARLY AGE BINGE DRINKERS? >> ABSOLUTELY. I THINK THAT THERE ARE OTHER EQUALLY ROBUST RISK FACTORS FOR HEAVY DRINKING AND DRINKING PROBLEMS. A DIFFERENT PARADIGM LOOKING AT A DIFFERENT SUBPOPULATION OF NON-ALCOHOLICS, WHO EARLIER IN THEIR DRINKING CAREERS ARE SHOWING THE RISING BLOOD ALCOHOL CURVE MORE STIMULATION, I BELIEVE THAT IS IMPORTANT, AND IT MAY BE THAT THE PREVENTION CHARACTERISTICS THAT ONE WOULD LOOK AT AS POTENTIAL MEDIATORS WOULD BE DIFFERENT THAN THE LOW RESPONSE TO ALCOHOL, AND AGAIN, INDIVIDUALS WITH HIGH LEVELS OF IMPULSIVITY SUCH AS PATRICIA KONROD'S WORK SAYS THAT THE CHARACTERISTICS THAT YOU MIGHT BE LOOKING AT FOR PREVENTION PROTOCOLS WOULD BE, AND VERY LIKELY TO BE, SOMEWHAT DIFFERENT THAN THOSE RELATED TO THE LOW RESPONSE TO ALCOHOL. SO IN SUMMARY, A BUNCH OF DIFFERENT CHARACTERISTICS THAT IMPACT ON EITHER INCREASING OR DECREASING YOUR PROPENSITY TOWARD ALCOHOL PROBLEMS, AND IT IS QUITE POSSIBLE THAT EACH OF THOSE CHARACTERISTICS HAVE SOME DIFFERENT MEDIATORS THAT YOU WOULD BE LOOKING AT IN AN ATTEMPT TO MORE HOLISTICALLY, REGARDING A CROSS OF BROADER RANGE OF RISK FACTORS, DIMINISH THE RISK AND PREVENTION PROGRAMS. >> AND MARC, THERE ARE PLENTY OF OTHER QUESTIONS AND WE'LL SEND YOU THEM IN EMAIL, BUT THE LAST QUESTION FROM HELENE LANGEVIN, HELENE ASKS, THERE ARE MORE QUESTIONS -- OOPS. WHERE DID IT GO? HOW DOES THE PROPENSITY TO DEVELOP/NOT DEVELOP NAUSEA/VOMITING INFLUENCE THE ALCOHOL RESPONSE? >> THAT'S A WONDERFUL QUESTION. IN OUR WORK, WHETHER ONE DEVELOPS A BAD HANGOVER AND THROWS UP THE NEXT MORNING DOES NOT, TO MY SURPRISE, SEEM TO BE RELATED TO WHETHER SOMEBODY IS RELATIVELY INSENSITIVE OR MORE SENSITIVE TOWARD ALCOHOL. SO IT'S A WONDERFUL QUESTION, AND THE PROBLEM IS, IF YOU DON'T GET SICK UNTIL THE NEXT MORNING, THAT IS NOT A VERY GOOD AVERSIVE RESPONSE TO TRY AND IMPACT ON WHAT YOU'RE GOING TO DO IN THE EVENING WHEN YOU'RE TRYING TO DRINK SOMETIME. BUT I THOUGHT IT WOULD BE RELATED TO THE LOW RESPONSE, BUT AT LEAST IN OUR WORK, THE PROPENSITY TOWARD HANGOVERS AND REALLY GETTING SICK WAS NOT RELATED TO THE SENSITIVITY TO ALCOHOL. >> MARC, THANK YOU SO MUCH. THIS WAS A WONDERFUL TALK AND GREAT QUESTIONS, AND I'M ETERNALLY GRATEFUL FOR YOUR WORK AND FOR YOUR WILLING TO PARTICIPATE IN THE SYMPOSIUM. SO WE'RE GOING TO MOVE ON NOW. SO I'M PLEASED TO PRESENT OUR NET DISTINGUISHED PRESENTER, DR. SUSAN TAP ERT FROM THE UC SAN DIEGO, USING MAGNETIC RESONANCE IMAGING, FUNCTIONAL MRI, DIFFUSION IMAGING AND NEUROPSYCHOLOGICAL TESTING. HER STUDIES ALSO EVALUATE ADOLESCENT BRAIN DEVELOPMENT, SEX DIFFERENCES AND SCREEN AND MEDIA USE. I MUST SAY SUSAN'S WORK HAS BEEN SO SEMINOLE THAT I'M CONSTANTLY USING HER RESULTS IN WRITING THAT I'M DOING ON ALCOHOL AND THE BRAIN, SO I'M EXCITED ABOUT HEARING HER TALK. HER PRESENTATION IS "ALCOHOL AND THE ADOLESCENT BRAIN: WHAT WE'VE LEARNED AND WHERE THE DATA ARE TAKING US." SO SUSAN, IT'S ALL YOURS. >> HI, I'M SUSAN TAPERT, AND I REALLY WANT TO THANK THE ORGANIZERS FOR INVITING ME TO PARTICIPATE IN THIS VERY EXCITING CELEBRATION OF THE 50TH YEAR ANNIVERSARY OF NIAAA. I'VE BEEN EXTREMELY GRATEFUL FOR SUPPORT FROM NIAAA FOR THE WORK THAT I HAVE CONDUCTED IN MY CAREER TO DATE. I'M GOING TO TALK WITH YOU TODAY ABOUT ALCOHOL AND THE ADOLESCENT BRAIN, WHAT WE LEARNED AND WHERE THE DATA ARE TAKING US. I'LL SHARE WITH YOU BACKGROUND ABOUT TYPICAL ADOLESCENT BRAIN DEVELOPMENT AND THE TYPICAL SUBSTANCE USE PATTERNS THAT OCCUR AT THIS TIME IN LIFE. HOW THE USE OF ALCOHOL MIGHT INFLUENCE THIS, AND THEN SOME OF THE NEXT STEPS THAT WE THINK ARE IMPORTANT IN THIS LINE OF RESEARCH. IN TERMS OF THE PREVALENCE OF SUBSTANCE USE DURING THE ADOLESCENT YEARS, WE LEARNED A LOT FROM THE ANNUAL MONITORING THE FUTURE STUDY, AND IMPORTANTLY WE SEE ALCOHOL CONTINUES TO BE A PRETTY WIDELY USED SUBSTANCE AMONG EET. THE YOUTH. THE PREVALENCE REALLY INCREASES FROM 8TH GRADE TO 12TH GRADE AND WE'RE REALLY INTERESTED IN LOOKING AT THIS DURING THE PANDEMIC RIGHT NOW TOO, TO SEE WHAT THE RATES ARE OF USING THIS INTOXICATING SUBSTANCE AND ONE THAT MIGHT BE SWA MORE SOMEWHAT MORE AVAILABLE TO KIDS WHO MIGHT BE HOME MORE THAN USUAL RIGHT NOW. WHAT'S IMPORTANT TO ME IS THE RATE OF KIDS WHO HAVE REPORTED GETTING DRUNK IN THE PAST MONTH. SO IT'S PRETTY INFREQUENT IN EIGHTH GRADE BUT STILL CONCERNING, AND BY 12TH GRADE, ALMOST 1 IN 5 KIDS REPORT HAVING GOTTEN DRUNK IN THE PAST MONTH. AND I'LL SHOW YOU HOW WE THINK THAT COULD BE REALLY IMPORTANT FOR BRAIN DEVELOPMENT. CANNABIS USE CONTINUES TO BE PRETTY WIDESPREAD AND VAPING HAS REALLY TAKEN OVER THE MARKET OF CIGARETTES FOR YOUTH AND IT'S THE MAIN WAY THAT A LOT OF YOUNG PEOPLE ARE USING CANNABIS IN RECENT YEARS. OTHER SUBSTANCES ARE USED LESS WIDELY BUT ARE CONCERNING AS WELL. AT? THIS TIME IN LIFE WHEN DRINKING TO INTOXICATION INCREASE, THERE ARE A LOT OF IMPORTANT DEVELOPMENTS HAPPENING WITHIN THE BRAIN. WHITE MATTER AND MYELINATION ARE CONTINUING TO DEVELOP PROMINENTLY, THE RATE KIND OF DISSIPATES GRADUALLY AS WE GET INTO THE YOUNG ADULT YEARS. AND THIS BROWN LINE SHOWS KIND OF THE RATE OF CHANGE OF GREY MATTER, SYNAPTIC REFINEMENT IS THE LIKELY PROCESS UNDERLYING THAT, AND THE RATE OF THIS PROCESS REALLY KIND OF INCREASES DURING THE LATE CHILDHOOD/EARLY ADOLESCENT YEARS AND THEN KIND OF BEGINS TO TAPER OFF. AND HERE'S SOME EVIDENCE FROM THE NATIONAL CONSORTIUM ON ALCOHOL AND NEURODEVELOPMENT IN ADOLESCENTS. WHERE WE SHOW HOW GREY MATTER VOLUMES KIND OF DECREASE OVER THIS PERIOD OF LIFE OF ADOLESCENCE, AND AT A PRETTY SIMILAR RATE FOR MALES AND FEMALES. AND WHITE MATTER VOLUMES ARE INCREASING OVER THIS PERIOD OF TIME AS IMPORTANT FIBER TRACKS ARE MYELINATING AND EVEN INTO THE TRANSITIONAL YEARS OF EARLY ADULTHOOD. SO IMPORTANT NEURODEVELOPMENTS SOME OF MY EARLY WORK IN THE EARLY ADOLESCENT ALCOHOL FIELD GOES BACK ALMOST 20 YEARS AGO NOW, A SERIES OF SMALL CROSS-SECTIONAL STUDIES THAT LED TO SOME LARGER STUDIES. THE FIRST WAS LOOKING AT HOW KIDS' BRAINS REACT WHEN THEY SEE PICTURES OF ALCOHOL. IN THIS CASE, WE FOCUSED ON ALCOHOL ADVERTISING AND FOUND THAT TEENAGERS WHO WERE ALREADY DRINKING, THEIR BRAINS REALLY LIT UP AS THEY LOOKED AT PICTURES OF ALCOHOL. ALCOHOL ADVERTISING. AND THAT ACTIVATION DISSIPATED WHEN THEY LOOKED AT PICTURES OF OTHER BEVERAGES, SUCH AS SODA ADVERTISEMENTS. AND THE GREATER THE DEGREE OF THEIR PERSONAL DRINKING, THE GREATER THE DIFFERENTIAL ACTIVATION TO ALCOHOL SPECIFIC ADVERTISING. WE LOOKED AT COGNITIVE PERFORMANCE OF ADOLESCENTS WHO WERE LIGHT DRINKERS AND HEAVY DRINKERS, WHO HAD BEEN VERIFIED TO BE ABSTINENT FOR A PERIOD OF DAYS, WE FOUND THAT THE HEAVY DRINKERS PERFORMED MORE POORLY THAN NON-DRINKERS ON BOTH VERBAL AND NON-VERBAL INFORMATION. ABOUT A 10% DIFFERENCE IN THEIR PERFORMANCE, WHICH IF YOU THINK ABOUT REAL LIFE AND PERFORMANCE IN SCHOOL, IT'S KIND OF LIKE THE DIFFERENCE BETWEEN AN A AND A B IN SCHOOL. IN THIS CROSS-SECTIONAL STUDY. IN THE EARLY 2000s, WE LOOKED AT HIPPOCAMPAL VOLUME AND SAW THIS IMPORTANT BRAIN REGION FOR SUBSERVING MEMORY FUNCTIONS WAS SMALLER IN YOUTH WHO WERE HEAVY DRINKERS THAN IN NON-DRINKERS. AND WE SAW SOME SEX EFFECTS TOO IN THAT BOYS WHO WERE HEAVY DRINKING IN THEIR TEENAGE YEARS HAD A LITTLE BIT SMALLER VOLUMES HERE IN THE PREFRONTAL CORTEX, WHEREAS FOR GIRLS WHO ARE HEAVY DRINKERS, THEY ACTUALLY HAD LARGER VOLUMES IN THIS REGION, SUGGESTING A POSSIBLE INTERACTION BETWEEN KIND OF STAGING OF NEURODEVELOPMENT THAT'S DIFFERENT BETWEEN THE SEXES WITH THEIR DRINKING PATTERN AT THAT TIME IN LIFE. AND LOOKING AT WHITE MATTER, WE SAW IN THIS CROSS-SECTIONAL STUDY THAT THE MORE INTENSE YOUNG PEOPLE'S DRINKING EPISODES HAVE BEEN, THE POORER THE QUALITY OF THEIR WHITE MATTER BASED ON DI FEUNGS DIFFUSION TENSOR IMAGING DATA IN SEVERAL REGIONS OF THE BRAIN, SEVERAL WHITE MATTER TRACKS. SO THOSE WERE CROSS-SECTIONAL STUDIES, WHICH WERE REALLY IMPORTANT FOR HIGHLIGHTING THAT LOOKS LIKE THERE'S SOME IMPACT OF HEAVY DRINKING DURING THE TEENAGE YEARS ON COGNITION AND ON BRAIN STRUCTURE AND FUNCTION, BUT WHAT'S REALLY IMPORTANT IS TO LOOK AT THE SAME INDIVIDUALS OVER A PERIOD OF TIME, AND PREFERABLY WHEN THEY ARE STARTING THIS PERIOD OF VERGS THAT THEY ARE ALCOHOL FREE AT THIS POINT, THAT THEY HAVEN'T STARTED TO DRINK. SO THEN WE CAN OBSERVE OVER TIME WHAT HAPPENS IN THOSE WHO INITIATE HEAVY DRINKING, AND THOSE WHO DO NOT, DO WE SEE SOME CHANGES IN THEIR NEURODEVELOPMENTAL TRAJECTORIES. SO IN THIS STUDY FUNDED BY NIAAA STARTING IN 2002, WE RECRUITED ALMOST 300 12 TO 14-YEAR-OLD NON-DRINKERS FROM SAN DIEGO AREA MIDDLE SCHOOLS, AND WE FOLLOW THESE KIDS ANNUALLY OVER TIME FOR MANY YEARS. THIS STUDY JUST ENDED LAST YEAR. AND WE CONDUCTED MRI SCANNING, NEUROCOGNITIVE TESTING, DETAILED INTERVIEWS AND BIOSPECIMENS ABOUT THEIR SUBSTANCE USE AND OTHER INTERVIEWS AS WELL. AS TIME PROGRESSED, WE SAW THAT A PORTION. SAMPLE REMAINED NON-USERS. SOME INITIATED RELATIVELY HEAVY PATTERNS OF DRINKING, AND SOME BECAME KIND OF MODERATE DRINKERS ORGAN TO USE SOME OTHER SUBSTANCES. SO THIS PROVIDED A NATURALISTIC DESIGN TO LOOK AT CHANGES OVER TIME AND NEURAL MARKERS AND IN COGNITIVE FUNCTIONING, AS A FUNCTION OF ALCOHOL INITIATION. THIS WAS A PARTICULAR ANALYSIS LED BY DR. LINDSAY SQUEGLIA. THIS WAS HER MASTERS THESIS IN GRAD SCAT COOL HERE GRADUATE SCHOOL IN SAN DIEGO. IN THIS LENGTHY BATTERY OF NEUROCOGNITIVE TESTS THAT WE GAVE TO ALL THE KIDS IN THE STUDY, WE FOUND CERTAIN TASKS WERE AFFECTED FOR FEMALE AS A FUNCTION OF HAIR DRINKING THEIR DRINGING AND DRINKING AND OTHER TASKS AFFECTED FOR THE MALES. FOR FEMALES, THE MORE DRINKS PER MONTH THEY STARTED TO HAVE, THE WORST THEY DID OVER TIME IN THEIR PERFORMANCE ON A PICTURE MEMORY TASK. BOYS WHO STARTED TO DRINK WEREN'T PARTICULARLY AFFECTED ON THAT TASK, BUT INSTEAD WERE AFFECTED ON THEIR PER PERFORMANCE OF TASKS OF ATTENTION. SO SOME OF THESE ATTENTION TESTS ARE TASKS WHERE YOU HAVE TO PAY ATTENTION FOR SEVERAL MINUTES OF TIME AND IN A VERY FOCUSED MANNER, CROSS OUT A PARTICULAR THING ON THE PAGE. BOYS WHO STARTED TO DRINK MORE HEAVILY OVER THESE YEARS OF OBSERVATION, EVEN DRINKS TO THE POINT THEY SOMETIME HAD HANGOVERS, WENT DOWNHILL OVER TIME IN THEIR ABILITY TO PERFORM ON THESE TASKS. SOME JOBS DO INVOLVE FOCUSED PERSISTENT ATTENTION, AND IF THIS IS GETTING DISADVANTAGED BY HEAVY DRINKING, THAT'S PRETTY IMPORTANT. ANOTHER GRADUATE STUDENT IN OUR LAB, TAM HERE WE'RE LOOKING AT KIND OF EXTREME BINGE DRINKING EPISODES WHICH ARE LESS PREVALENT BUT PRETTY IMPORTANT, MONITORING THE FUTURE, FOR EXAMPLE, SHOWS THAT QUITE A FEW 17-YEAR-OLDS IN THE PAST TWO WEEKS REPORT HAVING HAD A BINGE DRINKING EPISODE WITH FIVE OR MORE DRINKS AND 11% HAD 10 OR MORE DRINKS ON AN OCCASION, WHICH IS QUITE CONCERNING. IN OUR STUDY, WE CLASSIFIED FOLKS BASED ON THEIR DRINKING PATTERNS AS EITHER A MODERATE DRINKER WHO HAD NEVER HAD A BINGE DRINKING EPISODE, A BINGE DRINKER WHO HAD FIVE OR MORE DRINKS ON AN OCCASION MULTIPLE TIMES AND ALSO FOLKS WHO WERE EXTREME BINGE DRINKERS WHO HAD HAD 10 OR MORE DRINKS ON AN OCCASION. WE LOOKED AT HOW THEY PERFORMED DIFFERENT ASPECTS OF VERBAL LEARNED AND MEMORY. FINDING THAT THOSE WHO ENGAGE PARTICULARLY IN BINGE DRINKING IS SHOWN HERE IN THE BLACK REALLY WENT DOWNHILL OVER TIME ON HOW THEY PERFORMED ON THESE TASKS. SO CONTROLLING FOR BASELINE PERFORMANCE, THEY PERFORMED POST DRINKING INITIATION MUCH WORSE THAN EVEN THE BINGE DRINKERS OR JUST THE MODERATE DRINKERS IN THEIR ABILITY TO LEARN NEW VERBAL INFORMATION AND TO RETAIN THAT INFORMATION OVER A DELAY PERIOD. TAM ALSO LOOKED AT THE AGE OF ONSET OF ALCOHOL USE AS A FUNCTION OF PERFORMANCE AND COGNITIVE TASKS AND FOUND THAT FOR SEVERAL AREAS OF COGNITIVE PERFORMANCE, AN EARLIER AGE OF ONSET OF REGULAR DRINKING, WEEKLY OR MORE FREQUENT DRINKING, WAS LINKED TO POORER PERFORMANCE LATER ON THESE TASKS. ESPECIALLY THOSE TASKS THAT INVOLVED INHIBITING A RESPONSE OR THAT INVOLVE WORKING MEMORY, SO HOLDING INFORMATION IN MIND OVER A PERIOD OF TIME AND WORKING WITH THAT INFORMATION IN MIND. SO THIS SUGGESTS THAT THE EARLIER ONSET OF ALCOHOL USE, POTENTIALLY THE GREATER THE RISK TO THE BRAIN. SO PUTTING TOGETHER KIND OF A SERIES OF OUR STUDIES LOOKING AT BRAIN FUNCTION, COGNITION IN YOUTH BEFORE THE ONSET OF HEAVY DRINKING, AFTER JUST A YEAR OR TWO OF HEAVY DRINKING, AND AFTER MANY YEARS OF HEAVY DRINKING DURING THE ADOLESCENT YEARS, WE KIND OF PUT TOGETHER THIS MODEL WHERE WE SEE WITH BRAIN ACTIVATION IN PARTICULAR LOWER LEVELS OF ACTIVATION IN THOSE KIDS WHO LATER WOULD START TO DRINK, WE'RE SEEING THAT LOWER LEVEL OF ACTIVATION BEFORE THEY START TO DRINK. AFTER ONE OR TWO YEARS OF HEAVY DRINKING, WE SEE THAT THEY HAVE LOWER LEVELS OF ACTIVATION ON TASKS BUT ARE STILL ABLE TO PERFORM REASONABLY WELL, AND THEN AFTER MAYBE FOUR OR FIVE YEARS OF HEAVY DRINKING, WE OFTEN SEE THERE'S ACTUALLY LESS ACTIVATION DURING A COGNITIVE KIND OF A TASK, AS WELL AS POORER PERFORMANCE ON THAT TASK. SO WE SEE, THOUGH, THAT THERE'S SOME SIGNALS THAT THE KIDS WHO ARE GOING TO START TO DRINK HEAVILY LATER SHOW SOME DIFFERENCES IN NEURAL MARKERS BEFORE THE ONSET OF ALCOHOL USE. SO THERE'S SORT OF A BIDIRECTIONAL EFFECT, AND IT'S REALLY IMPORTANT TO CHARACTERIZE WHAT THOSE EFFECTS ARE IF WE WANT TO UNDERSTAND WHAT THE IMPACT OF ALCOHOL ON THE BRAIN IS. SO HERE'S AN ANALYSIS THAT WE DID WHERE WE LOOKED AT THE CHARACTERISTICS OF KIDS AT AGES 12 TO 14. THEY WERE ALL NON-USERS. AND LOOKING TO SEE WHO WOULD START TO DRINK MODERATELY TO HEAVILY BEFORE TURNING 18. IN THIS SAMPLE, WE HAVE 67 KIDS WHO REMAIN NON-USERS, 72 BECAME HEAVY DRINKERS OVER THIS PERIOD OF TIME, AND THIS WAS ANALYSIS LED BY LINDSAY, THE POSTDOC IN OUR LAB AT THAT TIME USING RANDOM ANALYSES AND WE FOUND A RANGE OF NEURAL FEATURES AS WELL AS DEMOGRAPHIC FEATURES DIFFERENTIATED WHO WOULD AND WHO WOULDN'T INITIATE MODERATE TO HEAVY DRINKING IN THE SUBSEQUENT FOUR YEARS. SO HAVING CHARACTERISTICS KIND OF LINKED TO AN ACCELERATED DEVELOPMENT, LIKE KIND OF LIKE A PRECOCIOUS NEURAL DEVELOPMENT BACK IN THOSE PRE-DRINKING YEARS WAS LINKED TO GREATER CHANCE OF DRINKING LATER. SO THINNER CORTEX IN SEVERAL AREAS, LOWER LEVELS OF ACTIVATIN DURING SOME COGNITIVE TASKS, OF COURSE BEING A BOY WAS LINKED TO -- HAVING PARENTS WITH A HIGHER INCOME, AND POORER PERFORMANCE ON SEVERAL COGNITIVE TASKS BEFORE THE ONSET OF HEAVY DRINKING IN THOSE SORT OF MIDDLE SCHOOL YEARS WAS LINKED TO GREATER CHANCE OF DEVELOPING MODERATE TO HEAVY DRINKING BEFORE TURNING 18 YEARS OLD. SO THEN LOOKING AT THE KIND OF FLIP SIDE OF THAT RELATIONSHIP, HOW DOES EMERGING ALCOHOL USE DURING THESE YEARS INFLUENCE NEURODEVELOPMENTAL PROCESSES DURING THIS PERIOD OF TIME, WE COLLABORATED AND FOUND AN INTERESTING PATTERN, WHERE COMPARED TO NON-DRINKING CONTROLS WHO REMAIN NON-DRINKERS THROUGHOUT ADOLESCENCE, THOSE WHO INITIATED HEAVY DRINKING DURING ADOLESCENCE SHOWED ACCELERATED REDUCTION OF THEIR GREY MATTER. SO REMEMBER DURING ADOLESCENCE, WE USUALLY SEE THAT BRAIN MATTER IS TYPICALLY REDUCING. THAT HAPPENED AT EVEN A GREATER LEVEL FOR THE KIDS WHO INITIATED HEAVY DRINKING DURING THIS TIME. TYPICALLY WE'RE SEEING MIGHT WHIET MATTER INCREASES IN THIS PHASE OF LIFE, AND WE SEE THAT ACCELERATION IN WHITE MATTER VOLUME WAS ATTENUATED. THEY DIDN'T HAVE AS MUCH APPARENT GROWTH IN THEIR WHITE MATTER AS WE WOULD EXPECT. SO THIS STUDY WAS A LITTLE SMALLER THAN WE WISHED IT WOULD HAVE BEEN TO BE REALLY CONFIDENT IN THESE RESULTS, SO WE WANTED TO HAVE OPPORTUNITIES TO LOOK AT THIS IN LARGER SAMPLES, AND WE WERE VERY FORTUNATE TO HAVE FUNDING FROM NIAAA TO LAUNCH THE NDID CANDA PROJECT, NATIONAL CONSORTIUM ON CLOL AND NEURODEVELOPMENT IN ADOLESCENCE. ADMINISTRATIVE LEADERSHIP COMES FROM SANDY, OUR DATA ANALYSIS RESOURCE, WE HAVE FIVE DATA COLLECTION SITES AROUND THE COUNTRY AT PITTSBURGH, SRI, DUKE UNIVERSITY, OREGON HEALTH AND SCIENCES UNIVERSITY, AND UC SAN DIEGO. AT NCANDA, WE DID SCHOOL AND COMMUNITY RECRUITMENT AT EACH OF OUR FIVE SITES, CAREFULLY SCREENED FOLKS, AND ENDED UP WITH A SAMPLE OF 831 12 TO 21-YEAR-OLDS THAT WEAVER NOW BEEN FOLLOWING FOR SEVEN YEARS AND HOPE TO FOLLOW FOR MORE YEARS. WE OVERSAMPLED FOR RISK CHARACTERISTICS FOR ADOLESCENT SUBSTANCE USE ISSUES IN THE SAMPLE, SO WE INCREASED OUR RECRUITMENT RATES OF THOSE WITH FAMILY HISTORY OF SUBSTANCE USE DISORDERS, EARLY DRINKING AND EXTERNALIZING KIND OF SYMPTOMS AS WELL. AND 50% OF THE SAMPLE IS REPRESENTATIVE, WITHOUT ANY OF THESE RISK FACTORS FOR ALCOHOL USE DISORDER. SO WE DO ANNUAL FOLLOW-UPS WITH THE 831 FOLKS IN THE STUDY WITH INTERVIEWS, NEUROPSYCHOLOGICAL TESTS, COMPREHENSIVE NEUROIMAGING SESSION, WE ALSO COLLECT DNA SAMPLES. SO WITH THIS LARGER SAMPLE, WE WERE ABLE TO OBSERVE SIMILAR KINDS OF PATTERNS OVER TIME, SO HERE WE LOOKED AT, AFTER TWO YEARS OF FOLLOW-UP, OF FOLKS WHO INITIATED HEAVY DRINKING, 62 FOLKS WHO INITIATED HEAVY DRINKING DURING THIS TIME AS COMPARED TO THE HUNDREDS IN THE SAMPLE WHO DID NOT INITIATE HEAVY DRINKING DURING THOSE AGES IN LIFE, AND AGAIN A STEEPER CORTICAL VOLUME REDUCTION FOR THOSE WHO INITIATED HEAVY DRINKING DURING ADOLESCENCE. THIS IS A PAPER PUBLISHED BY PFEFFERBAUM AND COLLEAGUES. WE SEE VERY SIMILAR PATTERN WITH THOSE WHO INITIATE HEAVY DRINKING SHOW ACCELERATED REDUCTION IN GREY MATTER OVER TIME. LOOK BEING AT WHITE MATTER CHANGES IN ADOLESCENCE, IT'S A FUNCTION OF ADOLESCENT HEAVY DRINKING, ZHOU AT SRI INTERNATIONAL JUST HAS A PAPER ACCEPTED IN JAMA PSYCHIATRY, AND HERE HE LOOKED AT WHITE MATTER QUALITY OF HEAVY DRINKING YOUTH WHO TRANSITIONED INTO HEAVY DRINKING DURING THE PERIOD OF OBSERVATION BOTH BEFORE AS SHOWN KIND OF IN THE BLUE AND AFTER THE HEAVY DRINKING ONSET IN THE CONTEXT OF THE TYPICAL NEURODEVELOPMENTAL TRAJECTORY OF WHITE MATTER IN HUNDREDS OF YOUNG PEOPLE WHO DIDN'T INITIATE HEAVY DRINKING. IN PARTICULAR HERE, WE'RE LOOKING AT FRACTIONAL -- REALLY AT THE QUALITY OF THE WHITE MATTER. WE SEE THERE'S KIND OF A MAJOR CHANGE THAT OCCURS AFTER DRINKING ONSET FOR THOSE WHO INITIATE HEAVY DRINKING DURING THIS PERIOD OF LIFE. THE EFFECT WAS STRONGER FOR THOSE WHO INITIATED DRINKING AT AN EARLIER AGE IN ADOLESCENCE AND THE FINDINGS WERE MOST PRONOUNCED IN THE GENU AND BODY OF THE CORPUS CALLOSUM, WHICH IS A VERY IMPORTANT WHITE MATTER TRACT THAT WE KNOW IS CONTINUING TO DEVELOP DURING THIS TIME. OTHER FEATURES, OF COURSE, IN ADOLESCENTS ARE VERY IMPORTANT TO CONSIDER TOO. IT'S NOT THE ONLY THING HAPPENS IN THE LIVES AND WORLDS OF THESE KIDS WHO WE WERE STUDYING. SOME ARE EXPERIENCING MULTIPLE TYPES OF TRAUMA. SEVERAL NCANDA INVESTIGATORS HAVE BEEN LOOKING INTO -- LOOKING AT EXPERIENCES OF CHILDHOOD TRAUMA AND HOW THIS MIGHT RELATE TO DRINKING LATER. SO SOME KIDS IN THE SAMPLE HAVE REPORTED HISTORIES OF ABUSE AND NEGLECT, AND IN JYOTI'S ANALYSES, SHE FOUND THE MORE INSTANCES OF ABUSE AND NEGLECT, THE GREATER THE CHANCE OF LOWER LEVELS OF CONNECTIVITY BETWEEN KEY REGIONS IN THE BRAIN, PARTICULARLY THOSE REGIONS THAT ARE IMPORTANT FOR COGNITIVE CONTROL AND SENSORY MOTOR CONTROL. AND THE GREATER THAT KIND OF DISRUPTION IN CONNECTIVITY, THE MORE EXECUTIVE DYSFUNCTION THAT WAS OBSERVED ON NEURO -- TASK, AND THAT IN TURN WAS ASSOCIATED WITH A GREATER CHANCE OF HIGHER RISK TO DRINKING LATER. WE'RE ALSO INTERESTED IN MOOD DISORDERS, WHICH ARE RELATIVELY COMMON IN THE ADOLESCENT STAGE LIFE, AND THIS ANALYSIS WAS CONDUCTED BY ALEJANDRO MERUELO, UNIVERSITY OF SAN DIEGO. IN NCANDA, WE LOOKED AT 692 OF THE PARTICIPANTS AT FACE BASTE LINE, BASELINE, AND ONE YEAR LATER, 100 HAD TRANSITIONED INTO MAJOR DEPRESSIVE DISORDER, WHO HADN'T HAD THAT IN THE PRIOR YEAR, AND THE REST REMAINING NON-DEPRESSED. ALEJANDRO FOUND THAT THOSE WHO WOULD LATER LEAD INTO DEPRESSION. AT THIS POINT IN TIME, THE FIRST TIME POINT IN THIS STUDY, HAD THINNER CORTICES THAN THOSE WHO WOULD REMAIN NON-DEPRESSED. SO IT COULD BE KIND OF A PREDICTOR OR A MARKER THAT IS SUGGESTIVE OF DEPRESSION LATER. SO IF WE PUT ALL OF THESE FINDINGS KIND OF TOGETHER, WE SEE A PATTERN WHERE THERE ARE PRE-EXISTING NEURAL FEATURES INCLUDING ONE'S SEX THAT CONTRIBUTE TO ONE'S KIND OF NEUROBIOLOGICAL MAKEUP, AND ALCOHOL USE AND ALCOHOL USE EFFECTS SUCH AS DRINKING TO THE POINT OF HANGOVERS, BLACKOUTS OR WITHDRAWAL, SEEM TO IMPINGE ON THESE NEUROBIOLOGICAL PROCESSES, AND THE KIND OF DEVELOPMENT THAT HAPPENS TO THESE PROCESSES OVER TIME. SO WE SEE WHAT LOOKS LIKE GREY MATTER COMPROMISE. A LOT OF TIMES WE'RE SEEING THIS IN FRONTAL REGIONS IN PARTICULAR WHERE THERE'S KIND OF AN ACCELERATED REDUCTION IN GREY MATTER OVER TIME. AND WITH WHITE MATTER, WE SEE FROM LOOKING AT WHITE MATTER VOLUME AND LOOKING KIND OF AT THE QUALITY OF WHITE MATTER, THAT THERE'S COMPROMISE TO THE WHITE MATTER AS WELL, THAT IT'S NOT KIND OF GROWING AND MYELINATING AT THE SAME EXTENT THAT WE WOULD EXPECT TO OBSERVE OVER THIS PERIOD OF LIFE. AS A FUNCTION OF ALCOHOL. IT'S POSSIBLE THEN THAT THESE IN TURN INFLUENCE COGNITION, MOOD AND AFFECT, AND COULD LEAD TO INCREASED CHANCE OF PROBLEMS IN ADULTHOOD. A REVIEW PAPER THAT RECENTLY CAME OUT FROM KELLY COURTNEY, AN ASSISTANT PROFESSOR IN OUR GROUP, KIND OF REVIEWED HOW MULTIPLE CAN AFFECT MULTIPE FUNCTIONS OF COGNITION, AND WE DO SEE A LITTLE BIT OF A DIFFERENT PATTERN FOR FEMALES THAN MALES, WHERE FOR FEMALES, OR WELL SEE THAT THE EMERGENCE OF HEAVY DRINKING, AND FOR MALE, WE SEE ATTENUATION OF ATTENTIONAL KINDS OF TASKS. BOTH SHOW POOR PERFORMANCE ON ABILITY TO LEARN, RETAIN NEW INFORMATION. SO SOME IMPORTANT THINGS THAT WE HOPE TO LOOK AT MOVING FORWARD, WE LOOK FORWARD TO DOING SO IN A LARGER STUDY AN OVER A LONGER PERIOD OF TIME. JUST MOVING BACK HERE, ONE THING WE HOPE TO LOOK AT FURTHER IN NCANDA IS THE EXTENT TO WHICH SOME OF THESE CHANGES WERE MET WITH ABSTINENCE. WE KNOW SOME PEOPLE JUST KIND OF NATURALLY MATURE OUT OF HEAVY DRINKING AS THEY GO THROUGH THEIR 20s, AND ALSO EXPERIMENTALLY, WE HAVE A FEW STUDIES WHERE WE'VE BEEN ABLE TO MOTIVATE PEOPLE TO STOP DRINKING FOR AT LEAST A BRIEF PERIOD OF TIME AND WE CAN OBSERVE SOME CHANGES AND HOPEFULLY RECOVERY OF THESE DEFICITS OVER THAT TIME. ALSO, WE WANT TO BE ABLE TO LOOK AT MORE INDIVIDUAL VARIABILITY OVER TIME, AND THE ABCD STUDY WILL AFFORD THAT POSSIBILITY. ABCD IS ONE OF THE LARGEST CHILD DEVELOPMENT STUDIES IN OUR COUNTRY, AND WE'RE VERY BRYCE PLEASED TO BE PLEASED TO BE PART OF THIS STUDY. 21 SITES AROUND THE UNITED STATES, WE'RE FOLLOWING THEM FOR A PERIOD OF 10 YEARS. THE STUDY STANDS FOR ADOLESCENT BRAIN COGNITIVE DEVELOPMENT. WE USED A KIND OF SCHOOL BASED RECRUITMENT OF A DIVERSE SAMPLE. WHAT'S GREAT NEWS IS WE HAVE PUBLIC DATA RELEASES EACH YEAR, AND WE JUST RELEASED OUR THIRD ROUND OF DATA LAST WEEK, SO YOU CAN GO TO THIS WEBSITE HERE, AND APPLY FOR ACCESS TO THE DATA, AND ANALYZE THE DE-IDENTIFIED DATABASED ON YOUR OWN INTERESTS. THE DESIGN OF ABCD IS AT ENROLLMENT AND AGE 9-10, WE DID NEUROIMAGING, ASSESSMENTS AND COLLECTING BIOSPECIMENS AND OTHER SELF-REPORT MEASURES. WE REPEAT THIS LENGTHY SEVEN-HOUR ASSESSMENT EVERY TWO YEARS. IN THE YEAR BETWEEN, WE DO A BRIEF FOLLOW-UP THAT DOESN'T INCLUDE NEUROIMAGING BUT INCLUDES NEURO -- AND THEN AT THE SIX-MONTH MARC BETWEEN THESE IN-PERSON ASSESSMENTS, WE HAVE A BRIEF KIND OF ONLINE OR PHONE INTERVIEW. WE DO THIS WITH THE YOUTH. WE ARE CONTINUING TO OPERATE DURING THE PANDEMIC IN BOTH NCANDA AND ABCD WITH SAFE PROCEDURES. WE'VE BEEN ABLE TO PORT A LOT OF WHAT WE DO TO REMOTE ASSESSMENT APPROACHES USING ZOOM AND SMARTPHONES AND OTHER AND TO SAFELY BRING FOLKS IN FOR NEUROIMAGING ASSESSMENTS. I WANT TO THANK OUR NCANDA TEAM WHO ARE TREMENDOUS TO WORK WITH. AND WHO HAVE MADE MUCH OF THE WORK I DESCRIBED POSSIBLE AND OUR TREMENDOUS TEAM AT UC SAN DIEGO, AND ALSO WANT TO THANK A LOT OF FOLKS IN NIAAA WHO HAVE MADE THIS RESEARCH POSSIBLE STARTING WITH ELLEN WITT, BEN XU, JOHN MAT OCHIK, ANTONIO NORONHA AND GEORGE KOOB THANK YOU SO MUCH FOR YOUR TIME TODAY. >> SO I'M NOW BACK AND WE'RE NOW WITH SUSAN TAPERT WHO HAS GRATEFULLY AGREED TO ANSWER QUESTIONS THAT HAVE COME UP FROM HER PRESENTATION. I'M GOING TO ACTUALLY LEAD OFF WITH A QUESTION, SUSAN, THAT INTRIGUED ME WHILE I WAS THINKING ABOUT SOME OF THE THINGS THAT UM JUST PRESENTED. SO WHAT ABOUT MARIJUANA AND ALCOHOL? I KNOW THERE'S SOME STUDIES ON MARIJUANA, AT LEAST ONES I'VE SEEN WHERE THERE WERE SOME MEMORY PROBLEMS IN ADOLESCENTS, AT LEAST ONES THAT WERE HEAVY USERS WHILE THEY WERE USING, BUT THE QUESTION I HAVE IS WHETHER THERE'S ANY DATA YET ON INTERACTIONS WITH ALCOHOL AND MARIJUANA AND WHAT YOUR THOUGHTS WOULD BE ON THAT. >> WE HAVE BEEN LOOKING AT THIS INTERACTION BETWEEN CANNABIS USE AND ALCOHOL USE DURING ADOLESCENCE. IT IS COMMON FOR PEOPLE WHO ARE DRINKING HEAVILY TO ALSO USE CANNABIS. WE HAVE SEEN CERTAINLY WITH CANNABIS USE AND WITH ALCOHOL USE DIFFICULTIES IN VERBAL LEARNING AND MEMORY, AND THE INTERACTION EFFECT IS SORT OF INTERESTING. IT'S A LITTLE BIT TRICKY TO TEASE THESE APART, THERE WERE A LOT OF KIDS THAT ONLY USE CANNABIS AND DON'T USE ANY ALCOHOL, AND IT DOES LOOK LIKE THERE'S SORT OF A DETRIMENTAL INTERACTIVE EFFECT. >> THANK YOU. DO YOU ALL -- I'M NOT SURE I SHOULD ASK THIS QUESTION, BUT MAYBE IT WILL HAPPEN NATURALLY WITH NCANDA, BUT WHAT ABOUT WHAT KATHERINE SHOWED EARLIER TODAY, WHERE THERE'S THIS REBOUND PHENOMENON, YOU COULD CALL IT A KIND OF COHORT PHENOMENON WHERE WE'VE BEEN SEEING THIS DECREASE IN DRINKING DURING ADOLESCENCE. ARE THERE PLANS IN THE FUTURE TO LOOK AT THAT 20 TO 30-YEAR-OLD AGE GROUP, AND GIVEN THAT THE FRONTAL CORTEX DOESN'T REALLY FULLY KICK IN UNTIL ABOUT 25, I WONDER WHETHER WE MAYBE SHOULD BE LOOKING ALSO AT THAT AGE GROUP AND WHAT YOUR THOUGHTS ABOUT THAT ARE. >> IT'S A GREAT POINT, GEORGE. IT'S ARILY IMPORTANT A REALLY IMPORTANT T IME IN LIFE WHERE FOLKS ARE POTENTIALLY SETTING THE STAGE FOR THEIR FUTURE CAREERS AND HIGHER LEVELS OF LEARNING, SETTING UP FAMILIES, AND THERE COULD POTENTIALLY BE SOME DETRIMENTAL EFFECTS TO TRANSITIONING INTO THOSE ROLES IF ONE HAS BEEN HEAVILY INVOLVED WITH ALCOHOL USE. IN NCANDA, WE DO HAVE CAPACITY TO BE ABLE TO LOOK AT THIS IN TERMS OF THEIR CONTINUED ALCOHOL USE PATTERNS, AND HOW THAT MIGHT ALTER THEIR VARIOUS IND KAY INDICATORS OF THEIR BRAIN FUNCTIONING AND COGNITIVE FUNCTIONING AS WELL. I'M REALLY INTERESTED ALSO TO SEE WA KIND WHAT KIND OF EMERGENCE OF MOOD DISORDERS AND OTHER KINDS OF MENTAL HEALTH CONDITIONS MIGHT BE A LITTLE BIT MORE VULNERABLE IF SOMEBODY HAS BEEN USING ALCOHOL AT A HIGH LEVEL THROUGHOUT THEIR ADOLESCENCE INTO THAT TRANSITIONAL PERIOD. >> OKAY, THANKS. BY ASKING YOU A COUPLE QUESTIONS WHICH ARE ON MY MIND, THE STREAM HAS STARTED TO FLOW HERE, SO THIS IS FROM ALISON LUNDERY. SHE SAYS GREAT TALK, YOU SPOKE ABOUT A WIDE VARIETY OF BRAIN MEASURES ACROSS MODALITIES AS WELL AS MANY REGIONS. IN YOUR WORK, WHICH REGIONS, WHAT MODALITIES AND WHAT TASKS HAVE BEEN MOST INFORMATIVE FOR PREDICTING ALCOHOL USE AND OUTCOMES? THAT MAY BE A WHOLE LECTURE UNTO ITSELF, SUSAN, BAW MAYBE YOU COULD QUICKLY NAIL A FEW OF THOSE. >> SURE. GREAT QUESTION, ALISON. FRONTAL REGIONS SHOW UP A LOT WHEN WE'RE LOOKING AT PREDICTING VULNERABILITIES TO DEVELOPING ALCOHOL PROBLEMS LATER. OTHER AREAS TOO BUT THAT'S PROBABLY THE NUMBER ONE REGION. AND IN TERMS OF COGNITIVE TASKS, LIKE FUNCTIONAL MRI TASKS, COGNITIVE CONTROL TASKS ARE PROBABLY THE MOST IMPORTANT THAT WE'VE SEEN FOR PREDICTING EMERGENCE OF DRINKING LATER. >> EDIE SULLIVAN IS SENDING NUGGIES, SO RICH AND SYNTHETIC, CALL OUT TO OUR COLLABORATION. RICHARD SAYS DR. TAI BERT, THANK YOU FOR AN EXCELLENT PRESENTATION. ARE YOU PROPOSING TO OBTAIN GENOME HAD BEEN WIDE DNA SEQUENCE DATA FOR THE 11,000 ABCD SUBJECTS, AND IF SO, WHEN MIGHT IT BE RELEASED? >> EXCELLENT QUESTION, RICHARD. THAT IS PLANNED. I'LL HAVE TO GET BACK TO YOU AND I CAN EMAIL YOU WITH THE SPECIFIC TIMELINE. >> DON'T SALIVATE TOO MUCH, RICHARD. FROM JOANNE, HAVE YOU OR ANYONE IN NCANDA OR ABCD LOOKED AT HEALTH OUT OUTCOMES OR IMMUNE -- PARTICULARLY THE HEAVY BINGE DRINKER, AND WHETHER HEALTHY IMMUNE CHANGES MIGHT BE ASSOCIATED WITH COGNITIVE [INAUDIBLE] >> THIS IS A GREAT QUESTION ABOUT KIND OF IMMUNE FUNCTIONING AND OTHER HEALTH OUTCOMES. WE HAVEN'T LOOKED AT THAT YET. WE HAVE BEEN TRACING DIFFERENT KIND OF HEALTH CONDITIONS AND I KNOW THAT SOME STUDIES, OTHER GROUPS WHO'VE LOOKED AT ADD ADOLESCENT HEAVY DRINKING LIKE REALLY HEAVY DRINKING DURING TEENAGE YEARS HAVE FOUND SOME THINGS LIKE BONE DENSITY ABNORMALITIES, GREATER PROPENSITY TOWARD BROKEN BONES WHICH OF COURSE IS SOMEWHAT ACTIVITY, OR JUDGMENT-RELATED, BUT WE'LL CONTINUE TO TRACK THOSE IN APCD AND IN ABCD AND IN NCANDA. >> DAVID SAYS SOME OF THE DEFICITS ASSOCIATED WITH EARLY EXPOSURE ARE -- DO YOU HAVE ANY PLANS FOR USING GENOMIC TOOLS TO DISENTANGLE THAT GENETIC COMPONENT? >> GREAT QUESTION, DAVID. WE'LL PROBABLY NEED TO CONSULT WITH YOU ABOUT HOW BEST TO DO THAT. IT'S CERTAINLY SOMETHING THAT COULD BE DONE IN ABCD. WE DO HAVE MONOZYGOTIC AND DIZYGOTIC TWIN PAIRS, ALSO SIBLINGS WHO AREN'T TWINS WITHIN THE STUDY AND WE HAVE GENOTYPING DATA WITHIN THOSE, SO IT COULD BE POSSIBLE. >> I'M SEARCHING TO MAKE SURE I'VE COVERED -- SO MAYBE SINCE THERE'S SO MANY QUESTIONS ABOUT ABCD AND WHERE THE DATA IS, MAYBE YOU CAN JUST REITERATE ONE MORE TIME, SUSAN, WHERE YOU CAN FIND AND HOW TO ACCESS THE DATA. I KNOW THAT'S A BIG PART OF ABCD'S CONTRIBUTION TO THE WORLD, IN FACT. >> IT REALLY IS. WE HAVE A REALLY RIGOROUS DATA SHARING POLICY AND PROCESS IN ABCD. SO EVEN US ABCD INVESTIGATORS, WE CAN'T PUBLISH DATA UNTIL THEY HAVE BEEN CURATED. WE JUST RELEASED THE THIRD DATA RELEASE OF ABCD A WEEK AGO, WEEK BEFORE LAST NOW, AND YOU CAN GO TO NDA.NIH.GOV, AND THEN SLASH ABCD, AND THAT WALKS YOU THROUGH THE PROCESS OF HOW YOU CAN APPLY FOR A DATA USE CERTIFICATION, SO THAT YOU CAN ACCESS THE DATA AND ANALYZE THEM. YOU HAVE TO GO THROUGH YOUR GRANT FUNDING INSTITUTION, SO THE UNIVERSITY OR RESEARCH INSTITUTE THAT YOU'RE PART. BUT WE'VE HAD MANY, MANY PEOPLE FROM PRETTY MUCH ALL CONTINENTS NOW ACCESSING THE ABC D-DAY TA AND AN INCREASING NUMBER OF PUBLICATIONS COMING FROM OUTSIDE OF ABCD INVESTIGATORS WHO ARE PUBLISHING ON THESE DATA. I CAN JUST ADD A LITTLE BIT OF WHAT'S INCLUDED IN THIS MOST RECENT DATA RELEASE. WE HAVE ALL OF THE IMAGING, COGNITIVE, SELF-REPORT, PARENT REPORT DATA, AND SOME GENOTYPING INFORMATION FROM THE FIRST TIME POINT IN ABCD. PRETTY MUCH EVERYTHING FROM THE ONE-YEAR FOLLOW-UP IN ABOUT HALF OF THE PARTICIPANTS, 2-YEAR FOLLOW-UP DATA AS WELL. PLUS THESE KIND OF BRIEF MID YEAR ASSESSMENTS THAT WE HAVE WITH THE KIDS AND THE STUDY ABOUT THEIR SUBSTANCE USE LEVELS. >> I'LL ASK YOU ONE MORE QUESTION. I WAS GOING TO ASK OF MARC BUT I THINK MICHAEL CHARNESS BEAT ME TO IT -- NO, IT WASN'T MICHAEL CHARNESS BUT SOMEONE ELSE BEAT ME TO IT. YOU KNOW, KATHERINE TALKED ABOUT A PUBLIC HEALTH RESPONSE TO THE COHORT -- WITH THE COHORT INTERACTION, AND I JUST WONDERING FROM YOUR PERSPECTIVE WITH THE BRAIN IMAGING AND ALL YOUR WORK WITH THE COGNITIVE EFFECTS IN ADOLESCENTS, WHERE WOULD YOU PUT IF YOU WERE ME, WHERE WOULD YOU PUT YOUR EGGS IN THE -- IN A PUBLIC HEALTH RESPONSE TO ALCOHOL MISUSE? I MEAN, PLAY ME FOR A MINUTE. >> IT'S A TOUGH ROLE. I WOULD LIKE TO SEE TREATMENT DEVELOPMENT LOOKING AT EASILY DI SEMINAL -- TO HELP MAKE THE LIFESTYLE MODIFICATIONS NEEDED TO AVOID ALCOHOL USE. WE'RE ALSO FINDING ALL KINDS OF DIFFERENT LITTLE THINGS THAT MIGHT BE ABLE TO HELP A LITTLE BIT WITH YOUNG PEOPLE'S ALCOHOL USE RATES, LIKE ANSI TELL CYSTINE, OTHER PEOPLE HAVE FIND OTHER KINDS OF MEDICATION, FAMILY APPROACHES, SO IF WE LOOK THESE DIFFERENT KIND OF APPROACHES TOGETHER, CAN WE SEE REDUCTIONS OF RISK AND DETRIMENTAL OUTCOMES IN YOUNG PEOPLE. >> YEAH, WE HAVE A LITTLE TIME SO I'M GOING TO AGREE WITH YOU, I MEAN, WHEN YOU TRY TO FIND TREATMENT FACILITIES AND PRANLS PROGRAMS FOR ADOLESCENTS, IT CAN BE QUITE CHALLENGING AND I DO AGREE WITH YOU THAT SOME ENERGY PUT INTO THAT WOULD BE VERY VALUABLE. ALL RIGHT. WELL, I THINK UNLESS MY PEOPLE WHO ARE SENDING ME QUESTIONS HAVE ANY MORE IN THE HOPPER THAT I'VE MISSED, I THINK WE MAY HAVE EXHAUSTED EVERYBODY WITH OUR SYMPOSIUM BY THIS HOUR OF THE DAY. I WANT TO THANK ALL OF YOU FOR YOUR PARTICIPATION. SUSAN, THAT WAS A GREAT TALK IF I DIDN'T SAY THAT ALREADY, I MEANT TO. SAME, MARC, AND SAME, KATHERINE. I THINK ALL OF YOU HAD NOTES THAT INTERSECTED WITH EACH OTHER, AND IT'S REALLY BEEN GREAT FOR ME TO SEE SOME OF THE UPDATES THAT WE'VE BEEN WORKING ON AND SUPPORTING. YOU KNOW, I LOOK FORWARD TO TOMORROW. I'M GOING TO SAY GOODBYE TO EVERYBODY, AND IF YOU HAVE FURTHER QUESTIONS OR I SOMEHOW MISSED YOUR QUESTION, OR WE DIDN'T GET TIME FOR YOUR QUESTION, PLEASE SEND EMAILS THE WAY YOU'VE BEEN SENDING THEM AND I KNOW THE SPEAKERS WILL BE VERY INTERESTED TO INTERACT. OKAY. WELL, THANKS AGAIN, EVERYBODY. IT WAS REALLY WONDERFUL, AND I'M REALLY GRATEFUL TO YOUR PARTICIPATION AND HELP.