MY NAME IS GEORGE KOOB, DIRECTOR OF NIAAA, ON BEHALF OF THE NATIONAL INSTITUTE ON ALCOHOL ABUSE AND ALCOHOLISM WELCOME TO THE 12th ANNUAL JACK MENDELSON HONORARY LECTURE. THIS LECTURE SERIES IS ATTRIBUTED TO JACK MENDELSON, A MY NEAR IN CLINICAL ALCOHOL RESEARCH WHO HELPED SHAPE OUR FUNDAMENTAL UNDERSTANDING ABOUT ALCOHOL USE DISORDER AS A MEDICAL CONDITION THAT CAN BE TREATED EFFECTIVELY. HE WAS A GENEROUS MENTOR FOR AN ENTIRE GENERATION OF YOUNG INVESTIGATORS, WHO HAVE GONE ON TO BECOME LEADERS IN THE FIELD, ONE OF WHOM WAS ME. HE. HE WAS ONE OF MY GUARDIAN ANGELS WHO KEPT AN EYE ON MY CAREER CAREER. AS WE CELEBRATE THE NIAAA'S 50th ANNIVERSARY, IT'S NOTEWORTHY HE WAS INSTRUMENTAL IN LAYING THE FOUNDATION OF MULTI-DISCIPLINARY RESEARCH WHEN HE SERVED AS DIRECTOR OF THE NATIONAL CENTER FOR PREVENTION AND CONTROL OF ALCOHOL PROBLEMS WITHIN THE NATIONAL INSTITUTE OF MENTAL HEALTH, AND THAT CENTER EVOLVED INTO THE NIAAA, AROUND 1970. IN HONOR OF HIS LEGACY THIS ANNUAL LECTURE SPOT LIGHTS THE ACCOMPLISHMENT OF THE OUTSTANDING INVESTIGATOR WHO HELPED ADVANCE ALCOHOL RESEARCH. I'M PLEASED TO ANNOUNCE THIS YEAR'S HONOREE, DR. SANDRA BROWN, PIONEERING WORK SHED LIGHT ON CONSEQUENCES AND TRAJECTORIES ASSOCIATED WITH ALCOHOL ADOLESCENT USE AND IMPLICATIONS FOR TREATMENT. SHE'S A DISTINGUISHED PROFESSOR OF PSYCHOLOGY AND PSYCHIATRY AT UNIVERSITY OF CALIFORNIA SAN DIEGO, THROUGHOUT HER CAREER SHE HAS FOCUSED ON UNDERSTANDING THE ETIOLOGY, PROGRESSION AND REMISSION OF SUBSTANCE USE DISORDERS, IN THE BROADER CONTEXT OF DEVELOPMENT USING LONGITUDINAL, AMONG FIRST RESEARCHERS TO DEMONSTRATE ADVERSE NEUROCOGNITIVE OUTCOMES OBSERVED IN YOUTH MAY PERSIST AFTER LONG-TERM ABSTINENCE, DEMONSTRATED VOLUNTARY INTERVENTIONS DEVELOPMENTAL TAILORED CAN BE SUCCESSFUL, SCHOOL SETTINGS ARE A KEY IN IMPROVING ACCESS TO PREVENTION SERVICES FOR YOUTH OF ALL BACKGROUNDS. DR. BROWN ALSO HELPED LEAD IMPLEMENTATION OF NATIONAL SCREENING AND EARLY INTERVENTION GUIDELINES FOR YOUTH, CONTRIBUTING AS ADVISER FOR NIAAA'S ALCOHOL SCREENING, PRACTITIONERS GUIDE AND HELPING US TO CRAFT A WORLD HEALTH ORGANIZATION TREATMENT STANDARDS FOR ALCOHOL AND OTHER SUBSTANCE USE DISORDERS. HAVING EMERGED AS A LEADER IN OUR FIELD, IN 2012 SHE HELPED ORGANIZE AND ESTABLISH NATIONAL CONSORTIUM ON ALCOHOL AND NEURODEVELOPMENT IN ADOLESCENTS. HER NATIONAL ROLE EXPANDED IN 2015 WHEN SHE BECAME CO-PRINCIPAL INVESTIGATOR OF ADOLESCENT BRAIN COGNITIVE DEVELOPMENT STUDY, KNOWN AS THE ABCD STUDY, THE LARGEST LONG-TERM STUDY OF BRAIN DEVELOPMENT AND CHILD HEALTH IN THE UNITED STATES. DR. BROWN HAS EARNED MANY ACCOLADES FOR HER WORK, SERVED AS PRESIDENT OF THE SOCIETY OF ADDICTION PSYCHOLOGY OF THE AMERICAN PSYCHOLOGICAL ASSOCIATION, A FELLOW IN THREE APA DIVISIONS, AND RECEIVED APA'S DISTINGUISHED SCIENTIFIC AWARD AND RECEIVED THE DEPARTMENT OF VETERANS AFFAIRS FIRST ANNUAL WOMEN MAKING A DIFFERENCE AWARD, AND FOR HER DEDICATION TO TRAINING THE NEXT GENERATION OF RESEARCHERS DR. BROWN RECEIVED THE ALAN MARLAT YOUNG INVESTIGATOR MENTORSHIP AWARD, RESEARCH FUNDING FOR 35 YEARS FROM NIAAA, IN ADDITION TO DR. BROWN'S RESEARCH ALSO HAS BEEN FUNDED BY THE NATIONAL INSTITUTE ON DRUG ABUSE, NATIONAL CANCER INSTITUTE, EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF HEALTH AND HUMAN DEVELOPMENT. TODAY WE'RE VERY PROUD TO HONOR -- BROWN WITH THE JACK MENDELSON LECTURE AWARD, FOR INCREASING OUR UNDERSTANDING OF HOW ALCOHOL AND OTHER SUBSTANCES IMPACT ADOLESCENT DEVELOPMENT AND HOW EFFECTS CONTRIBUTE TO OUTCOME THAT PERSISTS INTO ADULTHOOD. ON A PERSONAL NOTE I'VE KNOWN SANDY FOR MANY YEARS. WE TAUGHT IN THE SAME DEPARTMENT IN PSYCHOLOGY AT UCSD BUT OUR GREATEST ADVENTURE IS WHEN WE WERE BOTH ON COUNCIL FOR NIAAA AND POPPED IN A RENTAL CAR TO DRIVE OUT OF A HURRICANE DESCENDING ON WASHINGTON, D.C. AND WE MANAGED TO GET TO NEW YORK UNSCATHED. SO ONE OF MY FOND MEMORIES OF INTERACTIONS WITH DR. BROWN THAT DOESN'T INVOLVE SCIENCE. SO, WELL, SORT OF INVOLVES SCIENCE. SCIENTISTS ANYWAY. BEFORE I TURN IT OVER TO DR. BROWN PLEASE NOTE WE WILL BE HOSTING A QUESTION-AND-ANSWER SESSION AT THE END OF THE LECTURE, IF YOU WOULD LIKE TO SUBMIT A QUESTION PLEASE CLICK ON THE SEND LIVE FEEDBACK BUTTON WHICH IS LOCATED ON THE VIDEOCAST PAGE FOR THIS LECTURE. AND SO CONGRATULATIONS, DR. SANDRA BROWN. IF YOU WERE IN WASHINGTON WE WOULD GIVE YOU A PLAQUE AND BE TAKING PICTURES AND WE'LL HAVE TO DO THAT LATER. AND SHE'S ABOUT TO GIVE US A TALK NOW DISCERNING RISKS AND EFFECTS OF ALCOHOL IN THE MIDST OF ADOLESCENT DEVELOPMENT. SANDY, IT'S ALL YOURS. THANK YOU, DR. KOOB, FOR THE VERY KIND AND GENEROUS INTRODUCTION, IN PARTICULAR THANK NIAAA FOR THIS AMAZING AWARD. I HAD THE GOOD FORTUNE OF MEETING JACK MENDELSON, IN ADDITION TO PERSONAL CONTACTS HEARD MANY ENTERTAINING STORIES ABOUT HIS SUBSTANTIAL CONTRIBUTIONS AND PERSONAL CONNECTIONS AND KINDNESS TO THE LEADERS IN OUR FIELD THAT HAVE LED TO ADVANCES IN CLINICAL ALCOHOL RESEARCH AND IN TREATMENT. AND I'M VERY HONORED TO BE A SMALL PART OF HIS LEGACY TO THE FIELD. TODAY, I WILL BE COVERING FOUR TOPICS, A BIT ON ADOLESCENT DEVELOPMENT, HOW IT APPEARS ALCOHOL ADOLESCENTS PREFER ALCOHOL AS A DRUG OF CHOICE, THEIR INVOLVEMENT IN PROBLEMS, IN CLINICAL COURSE, MAKE SOME COMMENTS ABOUT FORMULATING DEVELOPMENTAL FRAMEWORKS FOR THE STUDY AND TREATMENT OF ALCOHOL AND OTHER SUBSTANCE USE PROBLEMS DURING ADOLESCENCE AND FINALLY GIVE SOME EXAMPLES FROM THE TWO CONSORTIA THAT DR. KOOB MENTIONED. LET'S START WITH ADOLESCENT DEVELOPMENT. I WILL NOTE THAT THE CONCEPT OF ADOLESCENCE WAS DEVELOPED IN THE UNITED STATES IN THE LATE 1800s, UP TO 1920. IF YOU WERE LIVING, SAY, IN SHAKESPEARE'S TIME, 16th CENTURY, 12 AND 13-YEAR-OLDS WOULD BE CONSIDERED ADULTS. IT WAS REALLY THE INDUSTRIAL REVOLUTION THAT LED TO THE MIGRATION OF CITIES, YOUTH WORKING OUTSIDE THE HOME, PUBLIC EDUCATION ADVOCACY, ET CETERA, THAT LED TO THIS NEW PHASE OF DEVELOPMENT. PARADOXICALLY PRIOR TO THAT PUBERTY CAME LATER BUT ASSUMPTION OF ADULT ROLES CAME EARLIER. AND DEPARTURE FROM PARENTAL SUPERVISION ALSO CAME EARLIER. SINCE MID-1800s PUBERTY INCHED BACK, THE ONSET AT LEAST, A YEAR FOR EVERY 20 YEARS ELAPSEED SUCH THAT IN 1995 AFTER A COMPREHENSIVE SURVEY OF THE U. S., DR. ANNETTE COINED THE TERM "EMERGING ADULTHOOD," THE ADDITIONAL EXTENSION INTO EMERGING ADULTHOOD WHICH REFLECTED THE DELAYED TRANSITION TO EMPLOYMENT, MARRIAGE, PARENTHOOD UP TO AGE 25. SO THIS IS A NEW CONCEPT, ADOLESCENCE. ADOLESCENCE IS A UNIQUE PERIOD OF DEVELOPMENT THAT'S MARKED BY A PUNCTATE BIOLOGICAL ONSET, PUBERTY, AND OFFSET COMPLETELY BEHAVIORAL, ASSUMPTION OF ADULT ROLES AND RESPONSIBILITIES. AS BOB ZUCKER WOULD SAY IT'S NOT A PASS-THROUGH PERIOD BUT PIVOTAL TIME IN THE LIVES OF YOUNG PEOPLE, FOR WE HAVE RAPID INCREASES IN KNOWLEDGE, SKILLS, NEW TYPES OF ENGAGEMENT, ALL OF WHICH DRIVE YOUTH TOWARD INDEPENDENCE. SALIENT SOCIAL ENGAGEMENT AND INCREASED RISK TAKING INCLUDING ALCOHOL AND OTHER SUBSTANCE AINVOLVEMENT, INITIALLY A PERIOD OF TIME WE BEGIN TO SEE THE ONSET OF CERTAIN PHYSICAL PROBLEMS AND EMOTIONAL PROBLEMS. IF WE LOOK ACROSS SPECIES, AND LOOK AT THIS PERIOD OF TIME, THIS ADOLESCENCE, WE SEE ACCELERATIONS IN ACTIVITY LEVEL, SOCIALIZATION, EXPERIMENTATION, AND RISK TAKING. THERE IS A MOVE TOWARD NEW INDEPENDENCE AND ACTIVITIES. IN PARTICULAR, IN HUMANS WE SEE DEVELOPMENT OF SELF REGULATION, WE VIEW THAT AS CRITICAL, INVOLVES NEUROPSYCHOLOGICAL SKILLS, BEHAVIORAL CHOICE AND CONTROL, AFFECT MANAGEMENT AND REGULATION, AND MANAGING ONE'S BEHAVIOR AT THE SAME TIME YOU'RE EXPOSED TO NEW ENVIRONMENTS. THE PAST 25 YEARS IN PARTICULAR WE HAVE SEEN MARKED AND RAPID CHANGES IN YOUTH BEHAVIOR, AND SOCIETAL IMPACT OF THOSE BEHAVIORS. FOR EXAMPLE, IN 2004 ONLY 58% OF TEENS HAD ACCESS TO BASIC CELL PHONE, BUT TODAY OVER 95% HAVE A SMARTPHONE. LIFETIME DRUNKENNESS HAS DECREASED FOR YOUTH, DOWN TO 70%, BUT OVER ALL SUBSTANCE USE REMAINED RELATIVELY STABLE, ALTHOUGH THE TYPES OF SUBSTANCES USED AND METHODS HAVE CHANGED. FEWER GET DRIVER LICENSE, MORE PLAY COMPUTER GAMES, TEEN BIRTH DECREASED, DEPRESSION INCREASES, OVER TIME WITHIN THE INDIVIDUAL NOT ONLY ALTER THE DEVELOPMENTAL DEMANDS BUT CHANGE LEARNING OPPORTUNITIES AND SOCIAL EXPERIENCES OF YOUTH. THESE BEHAVIORAL CHANGES OCCUR IN THE MIDST OF BIOLOGICAL CHANGES, INCLUDING NEURODEVELOPMENTAL CHANGES, AS THEY CONTINUE TO UNFOLD. FOR OVER 15 YEARS NOW WE'VE HAD EVIDENCE THAT THE BRAINS OF YOUTH EXHIBIT NEURO ANATOMICAL DIFFERENCE ACROSS AGES FROM CHILDHOOD TO ADOLESCENCE TO YOUNG ADULTHOOD. THIS DEPICTS FINDINGS AT NIH THAT DEMONSTRATED THESE AGE-BASED DIFFERENCES IN GRAY MATTER VOLUME. THIS IS THIS HAS BEEN VERIFIED AND EXTENDED IN NIH-FUNDED PAIN PROJECT WITH CHILDREN AT MUCH YOUNGER AGES. SO WHAT ARE SOME OF THE SALIENT CHANGES THAT ARE UNFOLDING IN THE BRAIN? SCHEMATICALLY REPRESENTED IN THIS FIGURE THERE ARE A NUMBER OF TYPES OF CHANGES FROM PRENATAL, POST-NATAL, THIRD DECADE. SYNAPTIC REFINEMENT, MYELINATION DIFFERENCES IN PARTICULAR ARE UNFOLDING OVER THE COURSE OF ADOLESCENCE. THUS, CHANGE IS THE NORM WHEN WE STUDYING ADOLESCENCE. TO ENSURE PRECISION IN STUDIES OF ALCOHOL IN YOUTH WE NEED TO BE MEASURING THE THINGS THAT CHANGE, THE PATTERNS OF INTERRELATED CHANGES TO ENHANCE OUR MODELS AND UNDERSTANDING OF ALCOHOL USE AND CONSEQUENCES. IF WE ARE TO IMPROVE EFFECTIVENESS OF PREVENTION AND TREATMENT. NOW, ALCOHOL ONSET AND RATES OF USE INCREASE DRAMATICALLY FROM AGES 12 TO 18, FROM EIGHTH GRADE TO 12th GRADE. AND ARE CONTEXT SPECIFIC. THESE RATES ARE SIGNIFICANT, REPRESENTING PAST MONTH USE, EIGHTH GRADERS, 8%, 30% BY TWELFTH GRADE, MAJORITY OF SENIORS ARE USING, HAVE LIFETIME USE, AND ONE IN FIVE ARE REPORTED BEING DRUNK IN THE LAST MONTH. THAT RATE ESCALATES TO 1 IN 3 AMONG COLLEGE STUDENTS. IT'S NOT JUST THE ONSET OF ALCOHOL CONSUMPTION THAT NORMATIVELY OCCURS BUT YOUTH DRINK DIFFERENTLY THAN ADULTSDZ, HALF AS OFTEN, UNDER 21 YEAR OLD AGE RANGE, BUT DRINK ON AVERAGE TWICE AS MUCH WHEN THEY DRINK. AND TO ADD TO THE RISK THEY MUST OFTEN DRINK QUICKLY, BEFORE, DURING OR AFTER EVENTS, TO DO SO IN AN UNSUPERVISED FASHION BECAUSE IT IS ILLEGAL. FURTHER ADDING TO RISKS ASSOCIATED WITH HEIGHTENED BLOOD ALCOHOL CONCENTRATIONS. IN MODERN SOCIETY, PARTICULARLY IN AMERICA, ALCOHOL IS NOW INTEGRATED INTO MANY OF THE CORE DEVELOPMENTAL TASKS. FOR EXAMPLE, MOVING THROUGH SCHOOL. 1 IN 3 YOUTH REPORT ALCOHOL HURT THEIR GRADES IN SOME WAY. IT'S INTEGRATED INTO SCHOOL ACTIVITIES, ACADEMIC PROBLEMS, THOSE WHO ARE USING HIGH LEVELS OF ALCOHOL REPORT LOWER INVOLVEMENT AND SCHOOL CONNECTEDNESS. IN BEHAVIORAL DOMAINS, SUCH AS DRIVING, 1 IN 5 YOUTH REPORT UNSAFE DRIVING RELATED TO THEIR ALCOHOL USE AND HALF OF THE SINGLE VEHICLE CRASHES ARE RELATED TO VOLUME INVOLVEMENT, INDEED INVOLVED IN INJURY AND DEATHS WITHIN VEHICLES. FINALLY ON THAT VERY IMPORTANT DEVELOPMENTAL DOMAIN OF NEW TYPES OF RELATIONSHIPS, STABLE FRIENDSHIPS OUTSIDE THE HOME, ROMANTIC RELATIONSHIPS, INITIAL SEXUAL ENGAGEMENT, EVEN HAVING CHILDREN, ALCOHOL IS INVOLVED. ONE IN TWO SAY THAT THEY REGRET BEHAVIOR IN THEIR SOCIAL BEHAVIOR UNDER THE INFLUENCE OF ALCOHOL, AND ONE IN FIVE REPORT ALCOHOL CREATED SOME TYPE OF RELATIONSHIP PROBLEM, INDEED INVOLVED IN EARLY, RISKY, UNWANTED SEX AS WELL AS DYSSYNCHRONY. OVER 10 MILLION YOUTH 12 TO 20 DRINK ALCOHOL, THE HIGHEST ONSET BEFORE 21, ONE IN THREE, ALCOHOL IS CONNECTED TO THE TOP THREE CAUSES OF DEATH FOR YOUTH. I KNOW THAT IF WE WERE TO LOOK AT ANOTHE DOMAIN THAT RELATES TO RISK BEHAVIORS THAT CARRY HEALTH AND MORTALITY CONSEQUENCES, LIKE VEHICULAR ACCIDENTS, WE WOULD SEE THE SAME REDUCTION IN PREVALENCE IN THE MID-20s WHICH SAYS SOMETHING ABOUT FACTORS, COMMON FACTORS THAT MAY BE INVOLVED IN REDUCTION OF SUCH RISK BEHAVIORS. SO, HOW SERIOUS IS ALCOHOL FOR HUMANS AND FOR ADOLESCENTS, SHOULD WE BE CONCERNED? ANIMAL MODELS ARE A SOURCE OF INFORMATION FOR US BECAUSE FROM THEM WE CAN SEE CROSS--SPECIES SIMILARITY, PROPENSITY FOR SELF ADMINISTRATION, DEPENDENCE, WITHDRAWAL, SUBSTRATES THAT ASSIST IN UNDERSTANDING NEURAL AND ENVIRONMENTAL CONTRIBUTORS AS WELL AS CONSEQUENCES. ANIMAL MODELS WITH RODENTS, FOR EXAMPLE, WILL CONSUME TWO TO THREE TIMES MORE ALCOHOL THAN ADULTS, PARTICULARLY IN MALES. WE SEE LESS SENSITIVITY IN ACUTE SEDATIVE MOTOR IMPAIRING AND SOCIAL INHIBITION EFFECTS BUT MORE SENSITIVITY TO THE REWARDING EFFECTS OF ALCOHOL, SOCIAL FACILITATION, DISRUPTION OF MEMORY, EXECUTIVE FUNCTIONS, AND IMPAIRMENT OF NEUROTRANSMISSION IN THE HIPPOCAMPUS AND CORTEX IN PARTICULAR. BINGES PRODUCE NEURAL INFLAMMATION, LONG LASTING MEMORY EFFECTS, AND VARIETY OF BRAIN REGIONS, AS WELL AS RETARDATION OF NEUROGENESIS AND SLEEP ALTERATIONS WHICH I'LL TALK ABOUT TODAY. PROLONGEDETHANOL PRODUCES LONGER TERM CHANGES IN THE CORTEX AND HIPPOCAMPUS. SO, ALCOHOL DEPENDENCE IN PARTICULAR PRODUCES PROBLEMS THAT ARE BEYOND MORTALITY, THINGS LIKE SCHOOL DROPOUT, DEPRESSION, ILLEGAL BEHAVIOR, UNWANTED OR RISKY SEX, AND WE BEGAN STUDYING ALCOHOL PROBLEMS WITH YOUTH IN TREATMENT. THEY HAD A SHORTER DURATION OF HEAVY ALCOHOL USE, FEWER HEALTH PROBLEMS THAN ADULTS BUT HAD MORE CONSEQUENTIAL RISK TAKING BEHAVIORS. TWO DECADES AGO, WE FOUND THAT ALCOHOL DEPENDENT YOUTH WITH THREE WEEKS OF ABSTINENCE WHILE THEY WERE ABLE TO LEARN AS MUCH VERBAL INFORMATION, NON-VERBAL INFORMATION IN STRUCTURED SETTINGS, WITHIN 20 MINUTES RETAINED 10% LESS RELATIVE TO AGE, GRADE, SES, FROM THE SAME SCHOOL. 20-MINUTE DELAY, 10% DECREASE ON VERBAL AND NON-VERBAL DOMAINS. WE'VE CONTINUED TO FOLLOW YOUTH WITH SUCH DIAGNOSES, WHO RECEIVED TREATMENT. THE GOOD NEWS IS TEENS DO ABOUT AS WELL AS ADULTS, OR AS POORLY AS ADULTS, DEPENDING ON PERSPECTIVE, AFTER THEY RECEIVE SUBSTANTIAL TREATMENT. AS A SURVIVAL CURVE SHOWS, ADOLESCENTS WITH THREE OR FOUR WEEK OF INPATIENT OR RESIDENTIAL TREATMENT DO AS WELL AS ADULTS, THE WHITE LINE BETWEEN THE RED AND GREEN LINES WHICH ARE ADULTS. HOWEVER, THOSE WITH CONCOMITANT MENTAL HEALTH DISORDER DO SUBSTANTIALLY POORER. THAT'S THE YELLOW LINE IN THE FIGURE. AND WHAT ARE THOSE COMORBIDITIES? DISRUPTIVE DISORDER LIKE CONDUCT OR ADHD, DEPRESSION OR ANXIETY, CLEARLY REDUCES STRESS BUT ALSO IMPACTS THEIR INITIAL RETURN TO ALCOHOL AND REPEATED USE. THEY MORE COMMONLY REPORT GREATER NEGATIVE AFFECT, MORE COGNIZANT BEHAVIORAL SYMPTOMS PRIOR TO INITIAL OR LATER RELAPSE EPISODE, NOTABLY ALMOST ALL RELAPSE YOUTH WHO RELAPSE WITHOUT MENTAL HEALTH DISORDER REPORT DOING SO IN THE SOCIAL CONTEXT, THERE ARE MANY MORE RELAPSES ALONE FOR THOSE WHO HAVE THESE TYPES OF CONCOMITANT PROGRAMS, THIS SHOWS TRAJECTORY OVER 10-YEAR PERIOD, ON AVERAGE 16 YEARS OF AGE WHEN WE FIRST STARTED THE STUDY AND 27 YEARS OF AGE AT THE END. WHAT YOU'LL SEE IS THERE ARE QUITE VARIABLE COURSE FOLLOWING TREATMENT FOR ADOLESCENTS. THE GREEN LINE HERE AT THE VERY BOTTOM YOUTH WHO ABSTAINED, USE VERY LITTLE ALCOHOL OVER THE ENTIRE PERIOD. BLUE LINE ARE MATCHED COMMUNITY CONTROLS. BUT YOU'LL ALSO NOTICE THAT WITH THE RED LINE THAT THERE'S A LATE ADOLESCENT RESURGENT PRIMARILY WITH ALCOHOL OR CANNABIS, OR MARIJUANA. THE GOLD LINE SHOWS YOUTH WERE ABLE TO MAINTAIN LOW LEVELS OF EXPOSURE IN THE FIRST 2 TO 4 YEARS AFTER TREATMENT THERE'S A MARKED INCREASE IN THE EARLY 20s WHEN DRINKING IS NOW LEGAL AND THEY TRANSITION OUT OF THE HOME. THERE'S A SURGE OF ALCOHOL, MARIJUANA, SUBSEQUENT OTHER SUBSTANCE INVOLVEMENT. I WANT TO NOTE APPEARED TO BE RESOLVING BY MID-20s, ON THE RIGHT SIDE OF THE SLIDE. OF NOTE, THERE'S A HEAVY DRINKING GROUP, THAT'S THE BLACK LINE, ACROSS THE LOWER THIRD OF THE CHART. THESE ARE YOUTH WHO ALTHOUGH THEY MAY HAVE USED OTHER SUBSTANCES BEFORE TREATMENT RESOLVED INTO DRINKING ONLY, 16% OF SAMPLES, THEY DID SO WITHOUT EXHIBITION OF ANY DIAGNOSTIC SYMPTOMS THAT ARE DEPENDENCE RELATED OVER THE COURSE OF THE 10-YEAR PERIOD. TWO GROUPS HAVE MUCH LOWER OR MUCH POORER OUTCOMES AT THE VERY TOP, YOU SEE THE GOLD GROUP, THE CHRONIC SEVERE GROUP, THAT SEEM TO JUST CONTINUE AT HIGH LEVELS OF MARIJUANA, ALCOHOL, OTHER INVOLVEMENT OVER THE 10-YEAR DURATION AND THE DARKER BLUE LINE GROUP THAT APPEARS TO DO WELL FOR THE INITIAL SIX MONTHS TO ONE YEAR BUT THEN GRADUALLY INCREASES PARTICULARLY WITH TRANSITION TO ADULTHOOD. SO, WE STUDIED NOT JUST THE YOUTH OUTCOMES BUT OUTCOMES ON JOBS, RELATIONSHIPS, FINANCIAL INDEPENDENCE, ET CETERA. AND ONE OF THE THINGS THAT STOOD OUT FOR US IN THIS STUDY IS THE HEAVY DRINKING GROUP, THE ALCOHOL ONLY GROUP, APPEARED TO BE DIFFERENT ONLY ON TWO DOMAINS, FROM THE ABSTAINERS AND THEIR COMMUNITY COMPARISON GROUP. THOSE WORDS, THEY TEND TO CHOOSE PARTNERS THAT WERE HEAVIER DRINKERS OR MAY HAVE HAD ALCOHOL PROBLEMS RELATIVE TO THOSE ABSTAINING GROUPS OR LOWER COMMUNITY USE GROUPS. AND NEUROCOGNITIVE DIFFERENCES, SUGGESTING THAT THE NEUROCOGNITIVE FUNCTIONING OF THOSE WHO CONTINUE TO USE ALCOHOL HEAVILY DURING THIS PERIOD OF TIME LOOKS MORE LIKE YOUTH WHO USE NOT JUST ALCOHOL BUT OTHER DRUGS, AND MET CRITERIA FOR DISORDERS. THE TOP TWO LINES ON THIS FIGURE, BLUE AND GREEN, REFLECT THE ABSTAINING AND COMMUNITY GROUPS, THESE ARE -- THIS HAPPENS TO BE COGNITIVE PERFORMANCE MODELED ON THOSE TRAJECTORIES AND CVLT MEMORY TASK, FREE RECALL RESULTS. SO SENIORS LOOK LIKE THE COMMUNITY TEAM, SEVERE CHRONIC GROUPS ALTHOUGH COMPARABLE TO NON-USERS AT THE BEGINNING OF PERFORMANCE, THOSE WITH LAID ADOLESCENT OR EARLY 20s RESURGENCE HAVE POORER OUTCOMES, HEAVY DRINKING GROUP IN PARTICULAR AS IMPAIRED AS THOSE WHO USED OTHER DRUGS. ALTHOUGH THEY AREN'T DIFFERENT ON BASELINE. THIS BEGAN OUR SEARCH TO DETERMINE HOW EARLY IN THE ALCOHOL USE CONTINUUM WE COULD IDENTIFY NEUROCOGNITIVE PROBLEMS AND MOOD DISRUPTION AS WELL. OF COURSE THERE MAY BE FACTORS THAT PRE-DATE THE ONSET OF HEAVY INVOLVEMENT THAT WILL INFLUENCE THIS COURSE, BUT THERE ARE TWO WAYS TO LOOK AT THIS. ONE TO BEGIN WITH YOUTH AND OBSERVE WHAT HAPPENS WITH THE ONSET OF DRINKING AND IN PARTICULAR BINGE DRINKING, ANOTHER APPROACH TO EVALUATE WHAT HAPPENS WITH THE OFFSET OF ABSTINENCE EARLIER ON. AND NEXT I'M GOING TO TELL YOU ABOUT THAT STORY. SO FIRST IN A LONGITUDINAL STUDY OF THE INITIATION OF DRINKING AND BINGE DRINKING, PROSPECTIVELY LOOKED AT BOYS AND GIRLS. STARTING AT AGES 12 TO 14, FOLLOWING THEM UP AT MUCH LATER POINTS IN TIME, DEMOGRAPHICALLY MATCHED AND AS WE LOOK THREE YEARS LATER WE CAN SEE THAT THE ONSET OF DRINKING PREDICTED REDUCTION IN PERFORMANCE IN VISUAL SPATIAL TASKS FROM BASELINE FOR GIRLS, THIS IS THE FREQUENCY OF DRINKING FOR GIRLS, AND FOR BOYS WHO REPORTED ONE OR MORE HANGOVER SYMPTOMS THERE WAS DETERIORATION IN ATTENTION. BOTH SHOWED LEARNING AND MEMORY CONSEQUENCES FROM THE ONSET OF HEAVY DRINKING. AND SIX YEARS LATER THEY HAVE IDENTIFIED EXTREME DRINKING, ABOVE 10 PER OCCASION, ASSOCIATED WITH DETERIORATED LEARNING AND MEMORY. IT INFLUENCE WAS ONSET, WHAT ABOUT OFFSET? WE STUDY YOUTH IN HIGH SCHOOLS WHO HAVE 50 OR MORE ALCOHOL USE EPISODES, BINGE DRINKING EPISODES IN THE LAST MONTH, ONE OR MORE WITHDRAWAL SYMPTOMS. AND BUT DID NOT MEET CRITERIA FOR ALCOHOL DEPENDENCE. AND WHILE THERE WERE POORER PERFORMANCES ON PROSPECTIVE MEMORY, INHIBITION TASK, ACCESS, VERBAL MEMORY, VISUAL SPATIAL CONSTRUCTION, SOME DOMAINS WE SEE MARKED IMPROVEMENT WITH ABSTINENCE. REPETITION AREAS ON THE CALIFORNIA LEARNING VERBAL TEST, ANOTHER IS VISUAL-SPATIAL PROBLEM SOLVING WHERE WE SEE DIFFERENCES BETWEEN MATCHED CONTROLS AT THE BEGINNING AND BINGERS THAT RESOLVE AT APPROXIMATELY THREE WEEKS AND CONTINUE TO RESOLVE SO THEY ARE COMPARABLE TO THE CONTROL POPULATION. WE LOOKED AT OTHER DOMAINS, LIKE MOOD CHANGES AND HOW PEOPLE RECOVER, YOUTH RECOVER AS WELL. HERE WE SEE THE GIRLS SHOWED POORER MOOD STATES WHICH PERSIST FOLLOWING ABSTINENCE IN BINGE DRINKING, BOYS MAY SHOW HIGHER SCORES INITIALLY AND DEPRESSION AND ANXIETY, NEGATIVE AFFECT, TEND TO RESOLVE TO THE NORMAL RANGE. WE DON'T KNOW, DO THESE FACTORS PRE-DATE THE ONSET OF ALCOHOL INVOLVEMENT WITH GIRLS SHOW IMPROVEMENT WITH LONGER PERIODS OF TIME, THESE ARE TYPES OF QUESTIONS THAT REMAIN UNANSWERED BUT SOME OF THE LARGER LONGER TERM LONGITUDINAL STUDIES SHOULD HELP US ADDRESS THIS. I WANT TO NOTE THAT THIS HEAVY EPISODIC OR CESSATION FROM HEAVY EPISODIC DRINKING CHANGES MOOD, COGNITION, BUT WHAT YOUTH ACTUALLY DO. FOR EXAMPLE, THIS SLIDE SHOWS THAT THOSE WHO HAVE A HISTORY OF BINGE DRINKING INCREASE IN THE AMOUNT OF TIME THEY SPEND READING OR DOING HOMEWORK DURING THE CESSATION PERIOD. THESE ARE HIGH SCHOOL STUDENTS, REMEMBER, WHO ARE NOT IN TREATMENT, JUST HIGH SCHOOL STUDENTS. AND THE SAME THING HOLDS FOR THOSE AREAS OF PHYSICAL EXERCISE AND SPORTS THAT OTHER BEHAVIORS CHANGE, MULTIPLE DOMAINS ARE CHANGING THE PROCESS OF ABSTINENCE AMONG NORMAL HIGH SCHOOL STUDENTS. LET'S MOVE TO -- GIVEN THIS IS THE CASE WHAT ARE SOME SEE CONSIDERATIONS FOR DEVELOPMENTAL FRAMEWORK OF ADOLESCENT ALCOHOL RESEARCH? ONE FACTOR IS ATTENDING TO CONTINUITY AND DISCONTINUITY THAT WE SEE OVER THE COURSE OF ADOLESCENCE AND INTO YOUNG ADULTHOOD. IT'S A NOTION THERE'S STABILITY WHILE THERE'S ONGOING CHANGE. SECONDLY, THERE'S TREMENDOUS HETEROGENEITY OF INDIVIDUAL TRAJECTORIES OR BEHAVIOR PHENOTYPES IN THE ONSET ESCALATION, OFFSET AND FLUCTUATION OF USE PATTERN. FROM DEVELOPMENTAL PERSPECTIVE YOU ALWAYS WANT TO TAKE A LIFESPAN PERSPECTIVE. MANY, MANY STUDIES LOOK ONLY AT PROXIMAL FACTORS, BUT DISTAL FACTORS SUCH AS FAMILY HISTORY OF ALCOHOL USE, EARLY TRAUMA, MAY INFLUENCE COURSE AND CONSEQUENCES. DEVELOPMENTAL TASKS AND TRANSITIONS THAT INFLUENCE BEHAVIOR AND SUCCESSFUL PERFORMERS. FINALLY, DEVELOPMENTAL FRAMEWORK CALLS FOR MULTI-SYSTEM OR MULTI-DISCIPLINARY APPROACH LOOKING AT BIOLOGICAL FACTORS, ENVIRONMENTAL FACTORS, GENETIC FACTORS, INTRAPERSONAL AND ASSOCIATE SOCIAL AND PERSONAL FACTORS. MAJOR ADVANCES IN ETIOLOGY AND COURSE OF ADOLESCENT ALCOHOL INVOLVEMENT WILL NOT LIKELY COME FROM THE DISCOVERY OF BRAND NEW RISKS, PROTECTIVE FACTORS, BUT PROBABLY FROM HOW THESE FACTORS INTERACT SUCH THAT THESE RISK PATHWAYS OR OUTCOME PHENOTYPES REFLECT CLUSTERS OF FACTORS OPERATING JOINTLY ACROSS THESE DOMAINS. JUST AS THE BEHAVIORAL PHENOTYPES, OUR INDIVIDUALITY, IF YOU WILL, WILL PERSIST OVER TIME AND MAY EVIDENCE CONTINGENT ON OPPORTUNITY AND CIRCUMSTANCE, FOR EXAMPLE CLUSTER TRAITS OR SKILLS OR HABITS. SO WHAT STRATEGIES MIGHT WE USE TO DETERMINE RISK IN THE MIDST OF THESE RAPID DEVELOPMENTAL CHANGES? WELL, CERTAINLY WE NEED TO MEASURE OVER TIME AND FREQUENCIES THAT APPROXIMATE CHANGES IN THE RISK OUTCOMES OF INTEREST. SO TIME SCALE REALLY MATTERS. SENSITIVITY IS NEEDED FOR MODEL SPECIFICITY, THAT IS WE NEED TO MEASURE BEFORE AND AFTER ONSET AND OFFSET, AND FREQUENCY TO ACCURATELY DETERMINE INDIVIDUAL AND ENVIRONMENTAL CHANGES. WE NEED TO MEASURE CORRELATES AND CONFOUNDS FOR THESE RISK PHENOTYPES TO TRULY UNDERSTAND THE ROLE OF ALCOHOL AND WHAT CAN BE ATTRIBUTED TO ALCOHOL'S EFFECTS. AND OUR PROCEDURES MUST BE REALISTIC, ACCEPTABLE, REPEATABLE MEASURES FOR ADOLESCENTS AND WE NEED TO RELY ON CONTENT EXPERTS. NOT JUST SCIENTISTS WE WORK WITH BUT ADOLESCENTS THAT WE'RE STUDYING TO ENSURE THEIR UNDERSTANDING AND THE ACCEPTABILITY OF OUR MEASURES. I DO ALSO WANT TO MAKE A COMMENT, THAT POLICY MAKES A DIFFERENCE. AT THE END OF THE OBAMA ADMINISTRATION THERE WAS A VERY IMPORTANT INITIATIVE, NATIONAL BRAIN INITIATIVE, THAT FOCUSED ON TECHNOLOGIES TO HELP US LINK GREATER SPECIFICITY AND BIOLOGICAL AND BEHAVIORAL SYSTEMS. THIS RESULTED IN ADVANCES IN NEUROIMAGING, EVEN IN THE VIEW OF NEUROGENESIS, FOR EXAMPLE. THERE ARE TECHNOLOGY ADVANCES IN BEHAVIORAL AND BIOBEHAVIORAL DOMAINS AND IT RESULTED IN A SURGE OF FOCUSED ON YOUTH ADISHES ADDICTION, AND THIS INITIATIVE RESULTED IN BOTH DATA AND COMPUTER SCIENCE ADVANCES, ALLOW GREATER POWER AND SENSITIVITY IN MODEL BUILDING AND ASSESSMENT. IT'S IN THIS FRAMEWORK THAT NCANDA WAS LAUNCHED, THAT DR. KOOB MENTIONED AT THE BEGINNING. CERTAINLY NIAAA'S LEADERSHIP ALLOWING THIS TO EVOLVE AND TO LINK EFFORTS WITH OTHER NIH INSTITUTES, NATIONAL INSTITUTE OF DRUG ABUSE, NATIONAL CANCER INSTITUTE AND NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT AS WELL. OUR NCANDA STUDIES TAKES PLACE AT FIVE SITES ACROSS THE UNITED STATES, LAUNCHED IN 2012, AND THERE ARE -- COORDINATING CENTER IS RUN BY SUSAN AND ME, AND YOU'LL SEE ALL THE INVESTIGATORS HERE AND A KEY SET OF SCIENTIFIC ADVISORS THAT HELP TO GUIDE US IN THIS PROCESS. I ONLY WANT TO MENTION NCANDA'S ORGANIZATIONAL STRUCTURE TO POINT OUT THAT THERE ARE MANY PEOPLE WHO ARE INVOLVED IN THIS PROCESS. THEY COME FROM DIVERSE BACKGROUNDS AND HAVE DIVERSE INTERESTS. BUT COLLECTIVELY EACH SITE AND THE CONSORTIUM STARTED WITH EXPERTISE IN HUMAN DEVELOPMENT, ADOLESCENT DRUG RESEARCH, NEUROCOGNITIVE AND NEUROIMAGING EXPERTISE, MULTI-SITE PROJECT EXPERIENCE, AND LONGITUDINAL RESEARCH. WE HAVE THE GOOD FORTUNE OF HAVING A NUMBER OF COMMITTEES AND WORKING GROUPS, AND STRONG EXTERNAL ADVISORY GROUPS SUCH THAT WE'RE ABLE TO MOVE SOME OF THE SCIENCE FORWARD. SO WHAT'S THE DESIGN FOR NCANDA? IT'S DEVELOPMENTAL IN FOCUS BY DESIGN. WE PAID ATTENTION TO THE IMPORTANCE OF DEVELOPMENTAL TAILORING, REPLICIABILITY AND GENERALIZATION OF NCANDA RESULTS. EACH OF OUR SITES, EXCUSE ME, NCANDA WAS BASED ON DEVELOPMENTAL HYPOTHESES, AND SCIENTIFIC AND CLINICAL EXPERTISE AND EXPERIENCE AT EACH OF THESE SITES. DATA ANALYTICS AND CORRAL LOUSE FOR EXCEPTIONAL DATA INTEGRATION, METICULOUS DATA HYGIENE AND QUALITY CONTROL SUCH THAT WE CAN FOCUS ON RESULTS-BASED ACCOUNTABILITY, CONSISTENCY AND STANDARDIZED BATTERY, CROSS-SITE TRAINING, MEASUREMENTS, AND ONGOING MONITORING. SO HOW DID WE DEVELOP THE YOUTH WHO ARE PARTICIPATING IN THIS IMPORTANT LONG-TERM STUDY? ACROSS THE FIVE SITES WE SELECTED 831 ADOLESCENTS, THAT CAME FROM SCHOOL AND COMMUNITY FLYERS, IN CATCHMENT AREAS OF SPECIFIC SCHOOLS, 7500 WERE SCREENED, 1400 MET OUR CRITERIA OF LITTLE OR NO USE WITH ONLY SMALL PORTION, 10 TO 15%, REPORTING DRINKING IN ADVANCE OF THE STUDY ACROSS THE AGES THAT WE INVESTIGATED. 53% OF THEM ARE COMPARABLE TO THE SES IN THEIR COMMUNITIES OF THESE FIVE SITES, AND THE OTHER HALF HAD ONE OR MORE RISK FACTORINGS, THINGS LIKE EXTERNALIZING SYMPTOMS, FAMILY HISTORY OF ALCOHOL OR DRUG PROBLEMS, OR HISTORY OF -- OR DISPLAY OF NEGATIVE SYMPTOMS. WE FOLLOW YOUTH ANNUALLY WITH INTERVIEWS, NEUROPSYCH TESTING, NEUROIMAGING AND BIOLOGICAL MEASURES. NCANDA FOCUSES ON EVALUATING EFFECTS OF ALCOHOL ON NEURODEVELOPMENTAL TRAJECTORIES, EFFECTS OF TIMING, DOSE AND DURATION ON BRAIN DEVELOPMENT, MALLEABLE EFFECTS WITH ABSTINENCE AND FACTORS FROM THE BIOPSYCHOSOCIAL DOMAIN THAT MAY INFLUENCE NEURODEVELOPMENT LIKE GENDER AND PUBERTY, FAMILY HISTORY OF ALCOHOLISM, TRAUMA, SLEEP. WE'RE LOOKING AT RISK PROTECTIVE AND RESILIENCY FACTORS FOR ADDICTION AND OTHER FORMS WHICH PARTICULAR MIND FOR THE IMPLICATIONS FOR EDUCATION, PREVENTION, INTERVENTION. THE SAMPLE IS ABOUT 2/3 CAUCASIAN, GOOD REPRESENTATION FROM AFRICAN AMERICAN AND HISPANIC POPULATIONS, AND OVER THE COURSE OF TEN YEARS OF STUDY WE WILL BE OBSERVING THESE YOUTH DURING THOSE KEY PERIODS OF TIME WHERE IT'S MOST LIKELY THEY WILL HAVE ONSET AND OFFSET OF ALCOHOL DISORDERS. SO WHAT ARE SOME OF THE THINGS THAT WE'VE FOUND? AS SHOWN IN MANY STUDIES NOW, BRAIN GREY MATTER AND CORTICAL FITNESS TEND TO DECLINE AMONG HEALTHY ADOLESCENTS. WE SEE BOYS IN BLUE, GIRLS IN RED. AND WHITE MATTER AND COHERENCE TENDS TO INCREASE, AGAIN BOYS IN BLUE, GIRLS IN RED. WE'VE ALSO FOUND THAT THOSE WHO CONTINUE AS LOWER OR NON-DRINKERS, GRAY MATTER DECLINES THROUGHOUT ADOLESCENCE (INDISCERNIBLE) WHITE MATTER REGIONS GREW FASTER AT YOUNGER AGES AND SLOWED TOWARD YOUNG ADULTHOOD AS WELL. THE IMPORTANT THING HERE YOUTH WHO INITIATE HEAVY DRINKING EXHIBITED ACCELERATED FRONTOCORTICAL DIVERGENCE FROM THE NORM. MARIJUANA USE APPEARED TO HAVE NO EFFECT NOR DID BASELINE VOLUMES. IT WAS THE CASE THAT PEAK PAST YEAR DRINKING AND FAMILY HISTORY OF ALCOHOLISM WERE ALSO ASSOCIATED WITH THESE CHANGES. SO IN CONCLUSION, WE CAN SAY THE INITIATION OF HEAVY DRINKING DURING ADOLESCENCE WITH OR WITHOUT MARIJUANA USE APPEARS TO DISRUPT NORMAL BRAIN GROWTH TRAJECTORIES IN INHIBITION AND INTEGRATION. BUT IN NCANDA WE DON'T JUST LOOK AT HOW THE BRAIN IS DEVELOPING. WE'RE LOOK AT CHANGES IN ADOLESCENCE AND FOUND FROM THE STUDIES COMING SRI AND DR. HEFFLER, AT BASELINE PREDICT OF ONSET OF YOUTH DRINKING, DIFFERENCES IN SLEEP ARCHITECTURE AND EEG ACROSS ADOLESCENCE, AND THERE ARE LINKS BETWEEN SLEEP AND BRAIN STRUCTURES. LONGITUDINAL CHANGES IN THE SLEEP ARCHITECTURE IN PARTICULAR ARE ASSOCIATED WITH HEAVY ALCOHOL USE. SIMILARLY, WHEN WE LOOK AT YOUTH WHO ARE EMERGING DRINKERS, RELATIVE TO THOSE WHO ARE NOT, WE SEE THAT THEY SHOW AN INCREASE IN SLEEP DISTURBANCE AND REM SLEEP, DECLINE IN NON-REM SLEEP OVER TIME COMPARED TO MATCHED CONTROL. ALCOHOL IS -- SLEEP MAY INFLUENCE INVOLVEMENT, ALCOHOL INVOLVEMENT MAY INFLUENCE SLEEP. WE KNOW THAT THERE ARE DEVELOPMENTAL SHIFTS AND PSYCHOSOCIAL RISKS, POSITIVE EXPECTANCY OR MOTIVATION AND PEER DRINKING ARE STRONGER INFLUENCE AND PREDICTORS IN EARLY RELATIVE TO LOWER ADOLESCENTS. IMPULSIVITY APPEARS TO BE STRONGER PREDICTOR OF EARLIER CONSUMPTION RATHER THAN LATER CONSUMPTION. IN COMPOSITE THESE FACTORS, THESE FINDINGS SUGGEST THAT RISK FACTORS MAY PRE-DATE, MAY CHANGE IN RELEVANCE AS YOU MATURE, AND CHANGE IN THEIR DEVELOPMENTAL TASKS, NEW ENVIRONMENTS, AND ROLE CHANGES. FINALLY I WANT TO MENTION THAT STRESS AND PARTICULAR TRAUMA APPEARS TO BE RELATED TO MODERATE -- ONSET OF MODERATE TO HEAVY ALCOHOL USE. IN OUR SAMPLE, APPROXIMATELY 50% HAVE EXPERIENCED TRAUMATIC EVENT SUFFICIENT TO TRIGGER CONSIDERATION. THINGS LIKE DEATH OF A FAMILY MEMBER OR FRIEND, EXPERIENCING A NATURAL DISASTER LIKE A HURRICANE, BEING MUGGED OR THREATENED WITH A WEAPON, SEVERE ACCIDENTS, WITNESSING A VIOLENT DEATH, SEXUAL ASSAULT OR ABUSE ARE THE MOST COMMON TYPES OF TRAUMAS THAT YOUTH ARE REPORTING. WHAT WE SEE IN THIS SLIDE IS THAT BASED ON THE -- WHETHER THEY HAD EXPERIENCED TRAUMA OR NOT, NO TRAUMA IS BLUE, ORANGE IS THEY EXPERIENCED TRAUMA BY BASELINE, AND THE GRAY HISTOGRAM IS TRAUMA AND ARE ALREADY EXHIBITING SOME POSTTRAUMATIC STRESS SYMPTOMS, THAT THOSE -- THERE ISN'T A DIFFERENCE EARLY ON BETWEEN THOSE WHO EXPERIENCED OR DIDN'T EXPERIENCE IF THEY HAVE NO SYMPTOM, YOUTH AT THE BEGINNING OF THE STUDY REPORTING POSTTRAUMATIC STRESS DISORDER SYMPTOMS ESCALATE IN THEIR MODERATE TO HEAVY DRINKING OVER FOUR YEARS, THE COURSE OF STUDY. TRAUMA ALONE, EVEN THE NUMBER OF TRAUMAS DIDN'T PREDICT TRANSITION INTO HEAVIER DRINKING. BUT THE EARLY RESPONSES OF THOSE WHO HAD EXPERIENCED TRAUMA APPEARS TO BE WHAT MAKES THE DIFFERENCE. NCANDA WE LOOK NOT ONLY AT BIOLOGICAL CHANGES AND ENVIRONMENTAL CHANGES, BUT WE'RE ACTUALLY TRYING TO DEVELOP NEW STRATEGIES FOR ENHANCING PRECISION OF OUR BEHAVIORAL MEASURES OF YOUTH AND FUNCTIONING IN THE NATURAL ENVIRONMENT. SO, FOR EXAMPLE, WE DEVELOPED WHAT'S CALLED M-NCANDA, MOBILE NCANDA APP WE'RE USING AT MULTIPLE TIME POINTS AND STUDIED THE USE OF THIS APP, REMEMBER OVER 95% OF YOUTH HAVE CELL PHONES, AND THIS HELPS US ASSESS A VARIETY OF TYPES OF THINGS, ALCOHOL AND OTHER SUBSTANCE USE, ACCESS TO THE SUBSTANCE, WHAT YOUTH ARE DOING ON A DAILY BASIS IN TERMS OF THEIR ACTIVITY, STRESSES THEY ARE EXPERIENCING, SOCIAL CONTACT, PHYSICAL ACTIVITY, HEALTH SUPPLEMENTS AND OTHER TYPES OF OVER-THE-COUNTER DRUGS AND QUALITY OF LIFE. THE M-NCANDA APP IS A DESIGN THAT'S ADAPTIVE BY NATURE, THAT IS YOUTH WHO ARE BEGINNING TO REPORT ALCOHOL USE MULTIPLE TIMES PER MONTH ARE ASKED ABOUT ALCOHOL AND OTHER SUBSTANCE INVOLVEMENT ON A WEEKLY BASIS BUT IF THEY ARE NOT USING THEN WE'RE NOT ASKING THOSE QUESTIONS, WE'RE ASKING QUESTIONS ON THE OTHER DOMAIN. TO COMPLETE THE APP TAKES LESS THAN A MINUTE. YOU CAN SEE BY THIS SLIDE THAT YOUTH FOUND IT ACCEPTABLE, SAME-DAY ASSESSMENTS ARE HIGHLY RELIABLE, MATCHES TO STRUCTURED INTERVIEW ASSESSMENTS, THERE'S GOOD ADHERENCE, AND LOW REACTIVITY TO THE COMPLETION. WHERE YOUTH INFORMED US THAT THEY COULD RESPOND MORE EASILY IF THEY COULD CHOOSE THE TIME OF DAY THEY ARE GOING TO RESPOND SO IT DOESN'T INTERFERE WITH WORK OR SCHOOL, DIFFERENT YOUTH PREFER DIFFERENT TYPES OF REMINDERS. ON OCCASION WITH YOUNGER YOUTH IN PARTICULAR PARENTS MAY CONFISCATE THEIR PHONES AND SO THAT'S A CONSIDERATION. AND SUGGESTIONS FOR CALENDAR ASSIST, SOMETHING THAT'S BEEN USED AND DEVELOPED IN NCANDA AND WE THINK WILL ADD TO THE PRECISION OF OUR MEASURES OVER TIME. ALL THESE TYPES OF DATA ARE RUN THROUGH THE DATA AND INFORMATICS RESOURCE CENTER THAT WE HAVE AT SRI, AND THE MODEL IS AN OPEN SCIENCE MODEL, SO UPLOADS ARE DONE QUICKLY, ALL THE DATA IS QUALITY ASSESSED AND THEN IMMEDIATELY AVAILABLE IN REDCap, AND RELEASED AFTER SIX MONTHS OF ANY PUBLICATION, AND TO GAIN ACCESS TO ANY OF THE DATA IN NCANDA YOU JUST APPLY TO NIAAA. IT'S, AGAIN, OPEN SCIENCE MODEL. I WANT TO ENCOURAGE PEOPLE TO CONSIDER OUTIZATION, A RESOURCE PARTICULARLY FOR JUNIOR INVESTIGATORS, PEOPLE NEW TO THE FIELD. DR. KOOB ALSO MENTIONED -- LET ME PAUSE AND SAY WHAT DO WE KNOW SO FAR ABOUT ALCOHOL AND YOUTH? WE KNOW THE BRAIN AND COGNITIVE SKILLS CONTINUE TO DEVELOP. THAT ALCOHOL OR BINGE DRINKING CAN PROVOKE POOR LEARNING AND MEMORY AND FOR ADOLESCENT GIRLS REDUCE VISUAL/SPATIAL FUNCTIONING, MALES PARTICULARLY THOSE WITH ANY HISTORY OF ANY WITHDRAWAL SYMPTOMS ATTENTION DECREMENT, ALCOHOL ACCELERATES GRAY MATTER REDUCTION, SLOWS WHITE MATTER DEVELOP, AS YOUTH ARE MOVING INTO ADULTHOOD, SELF-REGULATION. NOT ALL THESE EFFECTS ARE PERMANENT, THAT'S VERY IMPORTANT. THERE MAY BE SHORT-TERM USE CAN PRODUCE NEUROCOGNITIVE AFFECTIVE AND BEHAVIORAL CHANGES, BUT SOME OF THESE RESOLVE RELATIVELY QUICKLY, AND WE ALSO KNOW THAT RISKS AND IMPACTS VARY BY AGE AND STAGE OF DEVELOPMENT. SO, WHAT'S NEXT? WELL, I THINK WHAT'S NEXT IS POPULATION NEUROSCIENCE, AND THE LAUNCH OF ABCD. IT BECAME CLEAR WE HAVE AN EXTREMELY LARGE SAMPLE, OVER 800 IN NCANDA TO LOOK AT INTERACTIONS CRITICAL IN DEVELOPMENTAL MODELS, IT TAKES MUCH MORE THAN THAT ESPECIALLY IF WE'RE INTERESTED IN LOOKING AT ADDITIONAL ROLES OF GENETICS, AND OTHER ENVIRONMENTAL FACTORS. I'VE HAD THE GOOD FORTUNE TO WORK WITH TERRY JERNIGAN, MY CO-DIRECTOR OF THE COORDINATING CORE FOR ABCD, AND ANDRES DALE, AS WELL AS SUSAN TAPER, HUGH CARAVAN AND WES THOMPSON. THE IDEA TO PROVIDE A COMPREHENSIVE SURVEY OF DEVELOPMENT TO ALLOW STUDY FOR SPECIFIC GROUPS OF INTEREST, SUBGROUPS OF INTEREST THAT CAN BE MATCHED TO OTHERS IN THE PROJECT. TO HAVE THE POWER TO DETECT SMALL EFFECTS, INTERACTIONS, AFFORD REPLICIABILITY, TO REVEAL VARIABILITY WITHIN SUBPOPULATIONS AS IT RELATES TO SPECIFIC RISK FACTORS OR CONSEQUENCES OF SUBSTANCE USE, AND TO LOOK AT THE COMBINED GENETIC EPIDEMIOLOGY AND NEUROSCIENCE EFFECTS IN CONCERT. WE WANT TO FOCUS ON ROLE OF ENVIRONMENT AND GENETICS ON DEVELOPMENTAL, BOTH HEALTH AND DISEASE AND HOW THESE INFLUENCE DIFFERENCES ACROSS U.S. POPULATION. THIS REQUIRES ASSESSMENTS OF LARGE NUMBERS. SO, ABCD IS OF A DIFFERENT SCALE, AN OPPORTUNITY, AND CHALLENGE. THERE ARE 21 SITES ACROSS THE NATION INVOLVED IN ABCD. AND THIS EFFORT WAS LED BY NIDA, NIAAA WAS A STRONG SUPPORTER AS WERE 11 INSTITUTES AND CENTERS WITHIN THE NIH AND INSTITUTES OUTSIDE OF NIH. ALTHOUGH THERE ARE 21 SITES, THERE IS NO SITE THAT IS JUST A DATA COLLECTION SITE BECAUSE THIS IS BY DESIGN LED AS A TEAM SCIENCE EFFORT, SO COLLECTIVELY THE SITES GUIDE THE SCIENCE OF ABCD. SO, WE HAVE ALMOST 12,000 YOUTH AGES 9 TO 10 THAT WERE ENROLLED NATIONWIDE IN ABCD, THEY WILL BE FOLLOWED FOR TEN YEARS. WE HAVE A SCHOOL FOCUSED RECRUITMENT THAT WAS EPIDEMIOLOGICALLY GUIDED BY THE INSTITUTE OF SOCIAL RESEARCH, UNIVERSITY OF MICHIGAN. AND ADDITIONALLY, A PORTION FOUR SITES, TWIN COHORTS FROM STATE TWIN REGISTRIES, MULTI-MODAL, BEHAVIORAL ASSESSMENT, BIOSAMPLES, ENVIRONMENTS, AND ATTENDING TO NOVEL WIRELESS WEB-BASED AND OTHER TYPES OF TECHNOLOGIES FOR THE ASSESSMENT OF YOUTH FUNCTIONING. THE STUDY OBJECTIVES ARE TO DEVELOP STANDARDS FOR NORMAL BRAIN DEVELOPMENT. AND TO BE ABLE TO MEASURE INDIVIDUAL DEVELOPMENTAL TRAJECTORIES OF BRAIN AND COGNITIVE FUNCTIONING, EMOTIONAL DEVELOPMENT, ACADEMIC PROGRESS. IDENTIFY THOSE FACTORS THAT CAN INFLUENCE BOTH PROTECTIVELY AND ADVERSELY THE DEVELOPMENTAL OF THESE TRAJECTORIES. WE'RE INTERESTED IN BEING ABLE TO HAVE A SAMPLE SIZE THAT'S SUFFICIENT TO LOOK AT THE ROLES OF GENETIC AND ENVIRONMENTAL FACTORS ON DEVELOPMENT, INDEPENDENTLY AND COLLECTIVELY, AND STUDY IMPORTANT DOMAINS OF ADOLESCENT DEVELOPMENT, HELD, PHYSICAL ACTIVITY, SLEEP, SOCIAL ACTIVITIES, FOR EXAMPLE, AND HOW THESE MAY ALTER DEVELOPMENTAL OUTCOMES. WE'RE STUDYING ONSET AND PROGRESSION OF MENTAL HEALTH DISORDERS AND FACTORS THAT MIGHT INFLUENCE THE COURSE AND SEVERITY OF THESE DISORDERS AND RELATIONSHIP BETWEEN MENTAL HEALTH DISORDER AND SUBSTANCE INVOLVEMENT IN PARTICULAR INTERESTED IN DETERMINING HOW EXPOSURE TO PATTERNS OF SUBSTANCE USE MAY AFFECT DEVELOPMENTAL OUTCOMES AND VICE VERSA. OVER TWO-YEAR PERIOD WE WERE ABLE TO GARNER THIS LARGE SAMPLE OF YOUTH THAT APPROXIMATES THE U.S. CENSUS FOR YOUTH AT ABOUT 97%. YOUTH ARE STUDIED ON AN ANNUAL BASIS, IN PERSON ANNUALLY, AND MID-YEAR, VIA PHONE CALLS, AND EVERY TWO YEARS THIS INCLUDES MULTI-MODAL IMAGING AS WELL. AS ONE MIGHT IMAGINE, WITH THE ONSET OF SARS-COV-2 PANDEMIC IT'S BEEN A MAJOR CHALLENGE FOR BOTH NCANDA AND FOR ABCD. AND WE'VE HAD TO TRANSITION TO VIRTUAL ASSESSMENTS, THAT IS DOING ASSESSMENTS IN THE HOMES OF THE FAMILIES WE STUDYING AND I'LL SHARE EXAMPLES FROM ABCD BESIDES IMAGING AND NEUROCOGNITIVE THAT YOU HEARD ABOUT BUT THINGS THAT ARE NEWER AND REFLECT IMPORTANT ASPECTS OF YOUTH DEVELOPMENT. SO, FOR EXAMPLE, SINCE WE'RE STUDYING 9 TO 10 YEAR OLDS, LARGE COHORT OF THE 9 TO 20 YEAR OLDS, LOOK AT SEQUENCE OF SUBSTANCE INVOLVEMENT, ASKING QUESTIONS WHETHER THEY HAVE HEARD OF SOME OF THESE SUBSTANCES OR HAVE PEERS WHO ARE USING OR WE ASK ABOUT THEIR OWN USE, EVEN THOUGH THEY ARE VERY YOUNG DO RANDOM SAMPLES OF BIOSAMPLES TO TEST FOR USE FOR SUBSTANCES. HERE YOU'LL SAY THE MOST COMMON SUBSTANCE FOR YOUTH 9 TO 10 YEARS OF AGE WAS CAFFEINE, AND THEY USED ABOUT TWO DOSES A WEEK, AND 7% HAVE A DOSE, DAILY DOSE, DIFFERENT TYPES OF SODAS, TEAS, IN SOME CASES COFFEE ARE THE MORE COMMON TYPES OF SOURCES FOR CAFFEINE FOR THESE YOUTH. YOU'LL SEE BY THE SLIDE 22.5% OF YOUTH IN OUR SAMPLE HAVE SIPPED ALCOHOL, OF THOSE WHO HAVE SIPPED, ABOUT 2% HAVE ALSO PUFFED NICOTINE AND THOSE WHO ARE NICOTINE -- WHO USED NICOTINE, 60% HAVE SIPPED, ANYONE WHO HAS TRIED CANNABIS HAS ALREADY SIPPED ALCOHOL. WHERE DO THEY GET THESE SUBSTANCES, IN PARTICULAR ALCOHOL? 80% SAID MOM OR DAD GAVE THE SUBSTANCE TO THEM, OR ANOTHER ADULT WITH WHOM THEY KNEW. 3/4 WERE OFFERED, 4% SAID THEY TOOK IT. AND 93% SAID THEY REMEMBERED THESE EXPERIENCES, A SMALL NUMBER THAT WERE TOLD THAT THEY HAD CONSUMED ALCOHOL OR WEREN'T AWARE OF IT AT THE TIME. WE LOOK AT OTHER DOMAINS, UNDER LEADERSHIP OF MENTAL HEALTH WORKERS AT ABCD, PILOT AND IMPLEMENTED SUICIDAL IDEATION AND BEHAVIORS EARLY ON IN THE ASSESSMENT PROCESS. I THINK THE SUICIDE IDEATION SURPRISED US IN THE 9 TO 10 YEARS OLDS. YOU'LL SEE BASE RATES, BASE RATE OF REPORTED SUICIDE ATTEMPT WAS ONLY 1%, THE NON-SUICIDAL SELF INJURY WAS UP TO 9%. BOYS REPORT MOST TIMES OF SUICIDAL THOUGHTS AND BEHAVIORS, CAUCASIAN AND ASIAN AMERICANS REPORT HIGHEST LEVELS OF IDEATION, BLACKS OR AFRICAN AMERICANS ARE REPORTING HIGHEST NUMBER OF ATTEMPTS, AND HISPANICS IN OUR SAMPLE REPORT HIGHEST NUMBER OF SELF-INJURY BEHAVIORS. NOT SURPRISINGLY, FAMILY HISTORY OF SUICIDE IS ASSOCIATED WITH HIGHER LEVELS OF ALL OF THESE TYPES OF IDEATION AND BEHAVIORS. WE'VE BEGUN TO LOOK AT SCREEN AND MEDIA ACTIVITY, INITIALLY AND ABOUT 4500 YOUTH, THIS INCLUDES WATCHING TV, MOVIES, VIDEO GAMES, SOCIAL NETWORKING, VIDEO CHATTING, ET CETERA. SOME FINDINGS WERE NOT TOO SURPRISING THAT FAMILY CONFLICT MAY INCREASE IN A RELATIONSHIP TO SCREEN TIME AND SLEEP DISTURBANCE MAY INCREASE IN RELATIONSHIP TO SCREEN TIME. BUT TYPICAL ACTIVITY AND SOCIAL GAMING MEDIA REFLECTS A VERY DIFFERENT PATTERN, THAT IS YOUTH WHO ARE HIGHER IN SOCIAL GAMING MEDIA WERE ONES WHO WERE MORE ENGAGED IN PHYSICAL ACTIVITIES AND SPORTS. SO, MAYBE NOT ALL SCREEN MEDIA ACTIVITY HAS NEGATIVE CONSEQUENCES. WE KNOW SUCH ACTIVITY IS HIGHER AMONG BOYS, AND FAMILIES WITH LOWER PARENT INCOME AND EDUCATION, THOSE WITH HIGHER BODY MASS INDEX, AND SLIGHTLY HIGHER VISUAL CORTEX MATURATION. COMPLICATED RELATIONSHIPS WITH PSYCHOOLOGY, AND FLUID INTELLIGENCE CONSIDERED RELATIVELY PRELIMINARY AND WE'LL CONTINUE TO EXPLORE THESE AS WE MOVE FORWARD. I WANT TO END TODAY IN THE DATA PORTION OF THE STUDY BY USING THE CURRENT SARS-COV-2 PANDEMIC AS AN EXAMPLE OF THE KINDS OF DISCONTINUITIY THAT CAN HAVE CONSEQUENCES FOR YOUTH IN FAMILIES. THIS PANDEMIC IS AN OPPORTUNITIES FOR US TO OBSERVE NATURAL EXPERIMENT IN STRESS, IN SOME CASES TRAUMA IN PEOPLE'S LIVES. WITH FOUR NIH AND NSF-FUNDED SUPPLEMENTS, WE'VE BEEN ABLE TO CONDUCT OR ARE IN THE PROCESS THREE MONTHLY ONLINE SURVEYS FOR FAMILIES SAMPLING APPROXIMATELY 9,000 YOUTH, AGES 11 TO 14. AND FOR SMALL SUBPORTION OF THESE HAVE FIT BIT DATA OVER A FOUR-MONTH PERIOD. AND WHAT HAVE WE FOUND SO FAR? ALCOHOL USE -- 7% OVER THE THREE-MONTH PERIOD REPORTED USE OF SUBSTANCE, ALCOHOL ANDIBLE AND TOBACCO BEING MOST COMMON. ALCOHOL USE WAS ASSOCIATED WITH LESS PARENT EDUCATION AND THOSE PARENTS THAT WERE NOT MARRIED AT THIS TIME, AND YOUTH WITH HIGHER BASELINE EXTERNALIZING SYMPTOMS OR ADHD SYMPTOMS. IMPRTANTLY AS PARENT MONITORING CHANGED DURING THE PANDEMIC, THAT IS REDUCED, WE SEE A GREATER LIKELIHOOD OF INCREASE TO USE OF SUBSTANCES BY THE YOUTH IN THE PROJECT, AS PARENT MONITORING INCREASED, FOR EXAMPLE, PERHAPS THOSE PARENTS WHO ARE AT HOME, THERE'S A GREATER RATE OF STOPPING ANY USE. FOR FAMILIES WE KNOW THAT LOSS OF WAGES AND ECONOMIC HARDSHIP WAS RELATED TO INCREASED REPORTS OF FAMILY CONFLICT. AND THEN FINALLY GIRLS REPORTED MORE COPING RELATED STRESS AND WORRY THAN DID BOYS, AND ONSET OF THE PANDEMIC WAS ASSOCIATED REDUCED ACTIVITY AS MEASURED BY THE FIT BIT. SO, ABCD USES THAT OPEN SCIENCE MODEL I REFERRED TO, IT'S A BIG RESOURCE FOR THE SCIENTIFIC COMMUNITY BECAUSE BY POOLING THESE RESOURCES WE CAN CONDUCT DETAILED ANALYSES, ENRICHES VALUE OF ABCD STUDY AND THIS IS AVAILABLE TO ALL SCIENTISTS ON THE NATIONAL ARCHIVE, NIH ARCHIVE. THERE'S FAST TRACK DATA OF UNPROCESSED NEUROIMAGING AND PARTICIPANT DEMOGRAPHIC CURRENTLY AVAILABLE, AND ANNUALLY WE PROVIDE CURATED DATA UPDATES, AS WELL AS PROCESS TO HELP SCIENTISTS EXPLORE AND ANALYZE THE VOLUME OF DATA IN ABCD, IT'S A WEB-BASED INTERFACE, WITH CLOUD DEPLOYMENT. IT'S A PLATFORM, NATIONAL DATA ARCHIVE, DATA SHARING PLATFORM IS THE DATA SOURCE FOR IT. AND IT GIVES ACCESS TO ALL THE ABCD MEASURES, AND BUILDIN NESTING AND MULTI-LEVEL COVARIATES OF CHOSE AND ACCESS TO VERBALIZATION AND STAISTICAL MODELING TO HELP GUIDE USE OF ABCD DATA. SO, WHAT DO I THINK ABOUT DIRECTIONS GOING FORWARD? I THINK THAT THIS GREATER ACCESS AND FOR THE RESEARCH CONTINUITY CAN ACCELERATE SCIENCE. THESE TYPES OF LARGE SCALE PROJECTS LIKE NCANDA AND ABCD IN THE OPEN SCIENCE MODEL SERVE AS RESOURCES FOR THE COMMUNITY, PROVIDE DATA TO TEST DIVERSE HYPOTHESES NOT PART OF THE ORIGINAL INVESTIGATORS PLAN AND SERVE AS RESOURCE FOR COMPARISON POPULATIONS FOR INDIVIDUALS DOING OTHER STUDY. CAN FACILITATE NEW STUDIES SERVING AS PILOT DATA WHICH IS PARTICULARLY IMPORTANT FOR JUNIOR INVESTIGATORS, AND FOR PEOPLE WHO ARE NEW TO THE ADDICTION FIELD. SIZE OF DATASETS ALLOW FOR MORE COMPREHENSIVE AND ACCURATE MODELING THAT WILL BE IMPORTANT FOR THE IMPROVEMENT AND PREVENTION, EARLY INTERVENTION, TERTIARY INTERVENTION. FRANKLY SOME OF THE LARGE SCALE STUDIES ARE NEEDED BECAUSE OF COMPLEXITY, DEVELOPMENTAL COMPLEXITY THAT UNFOLDS OVER THE ADOLESCENT YEARS. THE MEASURES, PRECISION AND TIMING OF THESE ASSESSMENTS ARE CRITICAL TO THOSE MODELS, BUT NCANDA AND ABCD ARE NOT EXPERIMENTAL STUDIES. THEY ARE OBSERVATIONAL STUDIES WHICH SHOULD BY THEIR THE USE OF THEIR DATA LEAD TO HYPOTHESIS-DRIVEN EXPERIMENTS THAT CAN ANSWER IMPORTANT DEVELOPMENTAL QUESTIONS. ADVANTAGE OF THEM IS DATA QUALITY, MANAGEMENT, ANALYTIC ADVICE MAY CREATE OPPORTUNITIES FOR GREATER REPLICIABILITY OF THE SCIENCE THAT UNFOLDS UNFOLDS THROUGH THESE STUDIES. I WOULD LIKE TO CLOSE BY EXTENDING DEEP APPRECIATION TO ALL MY COLLABORATORS IN THESE PROJECTS OVER THE YEARS, MY KEY USCD COLLABORATORS, AND 75 FORMER AND CURRENT GRADUATE STUDENTS AND POSTDOCTORAL SCHOLARS, MUCH OF THEIR WORK IS WHAT I PRESENTED TODAY. DEEPLY APPRECIATIVE OF SUPPORT PROVIDED BY NIH IN PARTICULAR NIAAA AND NIDA AND OTHER ORGANIZATIONS AND CURRENT FUNDING FOR THE PROJECTS. WITH THAT, I WILL REMIND -- TURN THIS BACK OVER TO DR. KOOB AND REMIND PEOPLE OF THE WAY IN WHICH TO ASK QUESTIONS. THANK YOU ALL. >> THANK YOU, SANDY. I'M GIVING YOU A ROUND OF APPLAUSE, I'M ASSUMING EVERYONE LISTENING IS DOING. OUTSTANDING TALK, SO MUCH REALLY COOL INFORMATION RANGING FROM TRAJECTORIES THAT WE NOW KNOW ABOUT WITH ADOLESCENTS AND COMPLEXITY THAT ALL THESE FACTORINGS PLAY IN DEVELOPMENT, YOU KNOW, I GUESS ONE QUESTION, YOUR EXPERIENCE NOW, HOW RESILIENT ARE SOME OF THESE BRAINS OF YOUNG PEOPLE THAT HAVE BEEN EXPOSED TO ALCOHOL? YOU'VE SEEN THROUGH YOUR OWN WORK CHANGES WITH HEAVY DRINKING GROUP, YOU'VE SEEN NOW WITH NCANDA THOSE DRINKING HEAVILY AT THE ONSET OF THE STUDY. IS THERE HOPE, I GUESS THE SIMPLE WAY I WOULD PUT THIS QUESTION, AND I'LL GO TO THE QUESTIONS LINING UP IN THE CHAT BOX. >> GREAT QUESTION, GEORGE. I THINK THIS IS -- IT'S THESE TYPES OF DEVELOPMENTALLY PRECISE LONGITUDINAL STUDIES THAT CAN HELP US UNDERSTAND IMPROVEMENTS IN YOUTH. AND I DO WANT TO MENTION THAT WE'RE DOING THIS EVALUATION, IN NCANDA NOT JUST THROUGH THE OBSERVATION BUT THERE IS A PARTICULAR PROJECT THAT REPLICATES SOME OF OUR EARLIER INVESTIGATIONS OF LOOKING AT BINGE DRINKING YOUTH AND WHAT HAPPENS TO THEM IN THE FIRST FIVE WEEKS AFTER ABSTINENCE, YOU SAW IMPROVEMENTS ON SOME DOMAINS. NCANDA WILL HELP US UNDERSTAND FROM THEIR ORIGINAL BASELINE WHAT ACTUALLY IS IMPROVED. ARE THE DIFFERENCES THAT PERSIST AND ON SOME DOMAINS, VISUAL-SPATIAL MEMORY, FOR EXAMPLE, ARE THOSE A FUNCTION OF THE STARTING PLACE FOR THAT YOUTH AND WE DO SEE IMPROVEMENT, BUT THERE ARE DIFFERENCES THAT MAY HAVE IN FACT LED TO THE SUBSTANCE USE? OR WHETHER ANY OF THESE CAN BE RESOLVED. I THINK THESE QUESTIONS ABOUT NEUROCOGNITIVE FUNCTIONING, ABOUT THE IMPROVEMENTS IN MOOD, AND IMPROVEMENTS IN BEHAVIOR, ARE ALL THINGS THAT NCANDA WILL BE ABLE TO HELP US WITH IN THAT ACCELERATED COHORT DESIGN SO WE'LL HAVE SOME YOUTH WHO WE WILL BE ESSENTIALLY INCENTIVIZING TO REMAIN ABSTINENT FOR A PERIOD OF TIME AND WE WILL ALSO -- THERE'S THAT PORTION OF THE STUDY, AND THEN THE OTHER IS WE'LL BE ABLE TO LOOK AT CHANGES THAT UNFOLD IN RELATIONSHIP TO LENGTH OF ABSTINENCE THAT NORMALLY UNFOLDS FOR ADOLESCENTS, PARTICULARLY IN THE MID-20s. >> THANK YOU. THAT REALLY DOES HIT THE NAIL ON THE HEAD THERE. AND, YOU KNOW, I THINK THIS IS ONE OF THE MOST EXCITING PARTS OF THE LONGITUDINAL STUDIES. SO THE FIRST QUESTION WAS HAVE YOU BEEN ABLE TO IDENTIFY DIFFERENT PHENOTYPES BEING BETTER PREDICTORS AUD, SUD DEVELOPMENT BASED ON SEX/RACE/ETHNICITY? IF SO, WHAT ARE THE TOP THREE? AND WHAT IS/ARE THE TOP NEUROIMAGING PREDICTORS? >> YEAH, SO LET ME -- THANK YOU. THOSE ARE THE NEXT STEP QUESTIONS, AREN'T THEY? TO BE ABLE TO LOOK AT BEHAVIORAL PHENOTYPES THAT REFLECT THE CLUSTERING OF INDIVIDUAL CHARACTERISTICS. AND I WOULD SAY WE'RE IN THE PROCESS OF THAT. WE'VE IDENTIFIED INDIVIDUAL MEASURES THAT COLLECTIVELY MIGHT PREDICT THE ONSET OR RISK FOR BINGE DRINKING OR ONSET OF ANY DRINKING, BUT THE IMPORTANT THING WILL BE TO LOOK AT THESE IN CLUSTERS, MOST LIKELY THROUGH MACHINE LEARNING APPROACHES AND SUCH ANALYSES. I WOULD SAY THAT WHAT WE'RE EXPECTING IS THAT WE WOULD SAY, THAT WE WOULD EXPECT A MINIMUM OF TWO CLUSTERS, ONE WOULD HAVE TO DO WITH HIGHER RISK TAKING, EXTERNALIZING BEHAVIORS, IMPULSIVITY, ET CETERA. WE KNOW ABOUT THAT BUT THESE APPROACHES WILL HELP US UNDERSTAND ALL THE CHARACTERISTICS THAT FIT INTO THAT BEHAVIORAL PHENOTYPE. AND LEAD TO SUBSEQUENT USE. AND THE OTHER THAT'S BECOMING INCREASINGLY APPRECIATED AND DEMONSTRATED IN OVER SEVEN LARGE SCALE INTERNATIONAL STUDIES IS NEGATIVE AFFECTIVITY. THAT IS, A CLUSTER OF INDIVIDUAL CHARACTERISTICS, SUCH AS INITIAL SHYNESS, GREATER ANXIETY SYMPTOMS, ET CETERA, THAT MAY LEAD TO THE EQI-FINALITY OF ALCOHOL OR DRUG ENGAGEMENT OVER TIME. WE DON'T HAVE THE ANSWERS BUT I THINK IT WILL TAKE LARGE SCALE STUDIES LIKE NCANDA AND ABCD TO BE ABLE TO LOOK AT SOME OF THE SUBGROUP DIFFERENCES BEING SUGGESTED. WOULDN'T IT BE WONDERFUL TO KNOW THAT IN HISPANIC POPULATIONS, FOR EXAMPLE, THESE ARE THE THINGS TO LOOK FOR THAT ELEVATE YOUTH FOR GREATER RISK FOR INVLVEMENT AND FOR THE AFRICAN AMERICAN POPULATION BECAUSE THAT CAN HAVE IMPLICATIONS FOR BOTH POLICY AND PREVENTION. >> NO ARGUMENT FROM ME ON NEGATIVE AFFECT. NEXT QUESTION DEBRA SAYS THIS IS FROM BENZU, IF YOU CAN IDENTIFY WHO IS ASKING IT WOULD BE NICE TO SHARE THAT WITH THE AUDIENCE. WHAT ARE SOME OF THE KEY GAP AREAS IN RESEARCH NOT CRITICAL FOR UNDERSTANDING AND TREATING ADOLESCENT BEHAVIOR? >> YEAH, I THINK THAT THIS FRAMEWORK TO THINK ABOUT BEHAVIORAL PHENOTYPES CAN MAKE A TREMENDOUS DIFFERENCE BECAUSE ALTHOUGH BOTH NIAAA AND NIDA HAVE EXCELLENT GUIDELINES FOR TREATMENTS AND FOR LEVELS OF INTERVENTION, THIS PHENOTYPIC APPROACH MAY ACTUALLY OPEN VERY NEW DOORS. THERE MAY BE SOME YOUTH, FOR EXAMPLE, THAT MIGHT BE BETTER TREATED IN CERTAIN CONTEXTS, IN THE ACADEMIC CONTEXT, IN SCHOOL, FOR EXAMPLE, IN HIGH SCHOOL OR EVEN IN COLLEGE. WHEREAS OTHER YOUTH MAY BE MORE RECEPTIVE IN HEALTH CARE SETTINGS. ALSO, THERE ARE I THINK POLICY-RELATED ISSUES. FOR EXAMPLE, ONE OF THE THINGS THAT WE FOUND IN OUR STUDY THAT WHEN YOUTH MOVE OUT OF THE HOME, IT'S IMPORTANT WHERE THEY MOVE. THE NEW ENVIRONMENT CREATES RISK OR PROTECTIVE CONTEXT FOR ALCOHOL AND OTHER SUBSTANCE USE. NOW, THAT'S NOT ROCKET SCIENCE. BUT IF WE HAD LANDLORDS, FOR EXAMPLE, THAT HAD CERTAIN INFORMATION THAT WAS SHARED AT THE TIME AND EXPECTATIONS, THAT MIGHT MAKE A DIFFERENCE IN TERMS OF OPPORTUNITIES FOR INFORMATION AND FOR MOTIVATIONAL ENHANCEMENT BECAUSE IT REALLY IS ALL ABOUT CHANGING THE MOTIVATIONAL MATRIX FOR SUBSTANCE INVOLVEMENT. FOR THOSE WHO ARE NOT IN TREATMENT. AGAIN, REMEMBER, ONLY ABOUT 10% OF ADOLESCENTS OR YOUNG ADULTSD WHO MEET CRITERIA RECEIVE STRUCTURED TREATMENT FOR THAT DISORDER. >> THESE QUESTIONS, I'LL READ THEM TOGETHER, YOU PARTIALLY ANSWERED SOME. WHAT ARE SOME KEY CHALLENGES IN SUBJECTS ENROLLMENT AND RETENTION WITH A WIDE RANGE OF DEMOGRAPHIC POPULATION IN LONGITUDINAL STUDIES AND CHALLENGES IN MULTI-SITE IMAGING DATA HARMONIZATION AND SHARING? I KNOW YOU KNOW THE ANSWER TO THESE TWO BUT I'LL LET YOU GO FOR IT. >> SO CERTAINLY RETENTION IS KEY, IS IT NOT, FOR THESE LONGITUDINAL STUDIES, BECAUSE IT'S ONLY BY OBSERVING INDIVIDUALS OVER TIME AND WITH SUFFICIENT TEMPORAL SENSITIVITY THAT WE'RE GOING TO BE ABLE TO MEASURE CHANGES IN IMPORTANT EITHER RISK OR OUTCOME DOMAINS. SO, WE WORKED VERY HARD IN BOTH NCANDA AND ABCD TO ENSURE CONTINUITY IN OUR ASSESSMENTS OVER TIME, ENHANCING OUR FOLLOW-UP RATES. RAs MEET VIA ZOOM ON A WEEKLY BASIS. WE HAVE CALLS CALLED CHALLENGING CLINICAL SITUATIONS WHERE WE COLLECTIVELY REGARDLESS OF WHERE WE ARE IN THE UNITED STATES DISCUSS TYPES OF CHALLENGES THAT THE RESEARCH ASSISTANTS AND STAFF ARE FACING. AND WE NEED TO CONTINUALLY KEEP INDIVIDUALS INTERESTED IN THE STUDY. NOW, OF COURSE, FINANCIAL INCENTIVES KEEP PEOPLE INTERESTED. BUT OTHER THINGS AS WELL. THINGS SHOWING LIKE SHOWING A PERSONAL INTEREST IN THE SUBJECTS THEMSELVES BY CONTACTING THEM AT UNIQUE AND IMPORTANT TIMES FOR THEM PERSONALLY LIKE SENDING BIRTHDAY CARDS OR HOLIDAY CARDS, THAT TYPE OF THING. AND THEN CHANGING INCENTIVES AS YOUTH AGE. WE MIGHT HAVE GIVEN THEM PENCILS EARLY ON, WHEN THEY CAME IN BUT AT LATER POINTS IN TIME WE WILL DO ADAPTERS FOR THEIR CELL PHONES, T-SHIRTS AND ACTUALLY HAVE ARTS COMPETITIONS FOR IMAGES TO BE USED IN THE PROJECTS. THESE KINDS OF THINGS CAN MAINTAIN ENGAGEMENT BUT IT DOES TAKE ONGOING CHANGE AND DEVELOPMENTAL SENSITIVITY. IN ORDER TO ENSURE THAT, WE HAVE COMMUNITY LIAISON BOARDS FROM WHICH WE TRY TO GET ADVICE AND INFORMATION AND SOME OF THESE COMMUNITY LIAISON BOARDS INVOLVE YOUTH LIAISON BOARDS WHERE WE ASK DIRECTLY -- GET FEEDBACK FROM TEENS IN DESIGNING OR TAILORING INCENTIVES IN A WAY TO HAVE THE SUBJECT'S OPINION. MOTIVATIONAL INTERVIEWING IS REALLY THE KEY THAT UNDERSTANDING WHO MOTIVATES YOUTH TO CONTINUE TO PARTICIPATION AND BARRIERS FOR THEIR PARTICIPATION IS CRITICAL IN THE WAY WE ADDRESS ISSUES AROUND FOLLOW-UP. AND IT IS WITH THE CONSTELLATION OF STRATEGIES THAT WE THINK WE'LL BE ABLE TO MAINTAIN RELATIVELY HIGH FOLLOW-UPS. I WOULD NOTE THAT IN THE RECENT BLACK LIVES MATTER EFFORT ACROSS THE UNITED STATES IT'S BROUGHT SOME THINGS ABOUT CULTURAL SENSITIVITY TO OUR ATTENTION. AND WE AS RESEARCHERS TEND TO ALWAYS WANT TO USE THE SAME STRATEGIES, SAME APPROACHES OVER TIME, BUT I THINK THAT ATTENDING TO SOCIAL JUSTICE ISSUES IN THE MEANING OF THE MATERIALS WE'RE PRESENTING TO THE FAMILIES MAKES A BIG DIFFERENCE. FOR EXAMPLE, THERE HAVE BEEN EMERGENCY SITUATIONS WHERE ONE MIGHT THINK THAT IT'S WISE TO CALL 911 AND HAVE POLICE SHOW UP AT SOMEONE'S HOUSE. WELL, WE'RE NOW RETHINKING THIS AND CONSIDERING WHETHER WE CAN PRIORITIZE SENDING IN EMERGENCY SITUATIONS, SENDING RESOURCES IF THEY ARE AVAILABLE IN THE COMMUNITIES THAT INCLUDE MENTAL HEALTH PROFESSIONALS WITH POLICE BACKUP TO AFRICAN AMERICAN FAMILIES OR COMMUNITIES. WE REALLY NEED TO BE THINKING ABOUT ENHANCING CULTURAL SENSITIVITY TO MAINTAIN THOSE UNDERREPRESENTED MINORITIES. I'LL START WITH THAT. WITH REGARD TO NEUROIMAGING I'LL TRY TO BE BRIEFER, GEORGE, AND JUST SAY THAT WE ACTUALLY TRAVEL TO EACH SITE ANNUALLY AND HAVE WHAT WE REFER TO AS A PHANTOM TESTED IN THE MAGNET, SO THAT WE CAN ADDRESS SYSTEMATIC VARIABILITY ACROSS THE BRANDS OF IMAGING DEVICES THAT ARE USED AND SITE-SPECIFIC VARIABILITY AS WELL. THIS IS UNIQUE STRATEGY AS WELL AS REALTIME ASSESSMENT OF MOVEMENT IN THE MAGNET THAT ALLOWS US TO ENHANCE PRECISION OF THOSE MEASUREMENTS. IT'S THROUGH THOSE TYPES OF STRATEGIES THAT WE'RE ABLE TO COMBINE DATA FROM 21 SITES OR FROM FIVE SITES, AS IS THE CASE IN NCANDA, AND ACROSS DIFFERENT MAKES OR BRANDS OF IMAGING EQUIPMENT. >> THANKS. YOU'RE GETTING QUITE A FEW QUESTIONS LINED UP HERE SO I WANT TO GIVE YOU A HEADS UP ON THAT. THE NEXT ONE IS A BIT OF A ZINGER. WHAT KIND OF CHANGES MIGHT YOU SEE IF THE LEGAL DRINKING AGE WAS LOWERED TO 18 OR THE DRINKING AGE RAISED IN THE OTHER DIRECTION, WHAT WOULD YOU PREDICT? THAT'S THE QUESTION. YOU DON'T HAVE TO ANSWER THAT BUT THAT'S THE QUESTION. >> ACTUALLY I THINK THE QUESTION MIGHT BEST BE ANSWERED BY YOU, DR. KOOB. BUT ACTUALLY LET ME JUST SAY THAT I THINK OUR POLICIES HAVE AN IMPACT ON THE PERCEIVED ACCEPTABILITY OF SUBSTANCES. SO LEGALIZATION OF MARIJUANA WHICH IS UNFOLDING ACROSS THE NATION WITH NOW AT LEAST HALF OF THE STATES HAVING SOME FORM OF LEGAL CANNABIS USE. ALCOHOL USE, OR ALCOHOL USE BELOW AGE 21 WAS VARIABLE AT ONE POINT IN TIME. IF WE LOOK BACK HISTORICALLY AT CHANGES THAT UNFOLDED WITH THE RAISE OF THE DRINKING AGE THERE WAS A REDUCTION IN USE RATES. AND THEN SOMEWHAT OF A REBOUND AFTER THAT. I THINK THERE'S NO UNIFORM PREDICTION HERE. I THINK IT CAN MAKE -- IT WOULD MAKE A TREMENDOUS DIFFERENCE DEPENDING ON THE BEHAVIORAL PHENOTYPES AND THE IMPLEMENTATION OF THE POLICIES IN THE COMMUNITIES. SO ONE OF THE THINGS THAT WE ALL KNOW IS THAT YOU CAN HAVE NO ALCOHOL SALES TO MINORS POLICY BUT IF THE IMPLEMENTATION IS NOT CONSISTENT AT A LOCAL LEVEL, THEN IT MINIMIZES ITS EFFECTS. I WOULD SAY BY AND LARGE WHAT THE CURRENT FINDINGS ARE THAT WE SHOULD HAVE A GREAT PAUSE IN CONSIDERING LOWERING THE DRINKING AGE, OR FURTHER EXTENDING CANNABIS LEGALIZATION. >> ONE FALLACY I WOULD MENTION IS PEOPLE OFTEN MAKE THE ARGUMENT THAT IN EUROPE THEY TRAIN YOUNG PEOPLE HOW TO DRINK PROPERLY, THAT'S COMPLETELY FALSE. THEY HAVE THE BIGGEST PROBLEM, AS BIG A PROBLEM AS WE DO IN PROBLEM IN THE U.K. SO, THIS ONE IS THANK YOU FOR THE GREAT PRESENTATION. YOUR SLIDE REGARDING WHAT WE KNOW SO FAR ABOUT ALCOHOL AND YOUTH MAINLY FOCUSES ON HEAVIER BINGE DRINKING. MY IS HE MY QUESTION IS WHAT DO WE KNOW ABOUT MODERATE OR LOW LEVELS IN ADOLESCENTS AND THOSE 18 TO 20? THANK YOU. SO THAT'S THE QUESTION. >> YEAH, WELL, I THINK WE KNOW -- LET ME PUT THE FRAMEWORK HERE. THERE IS SUCH VARIABILITY IN RESPONSE TO ALCOHOL, AND TO THE RISKS FOR INDIVIDUALS THAT LOWER LEVEL OF ALCOHOL USE PRODUCE LESS UNIFORM RESPONSES. SO IT'S NOT QUITE AS EASY TO SAY WHAT THE RESPONSE IS TO LOW TO MODERATE LEVELS OF ALCOHOL USE. AND SOME OF OUR STUDIES, PARTICULARLY IN THE NCANDA STUDY, THERE IS INDICATION THAT MODERATE LEVELS OF ALCOHOL USE DOES -- WE CAN'T IDENTIFY NEUROANATOMICAL CHANGES OR SHIFTS IN TRAJECTORIES RELATED TO MODERATE LEVELS OF USE, NOT JUST BINGE DRINKING, FOUR TO FIVE DRINKS PER OCCASION, OR EXTREME BINGE DRINKING, TEN-PLUS DRINKS PER OCCASION, SO THE LONG-TERM OUTCOMES OF NCANDA I THINK GIVEN THE ACCELERATED COHORT DESIGN THAT WE HAVE WILL TELL US MUCH ABOUT THIS PARTICULAR ISSUE. LOWER LEVELS OF USE OVER EXTENDED PERIODS OF TIME. AGAIN, REMEMBER IN DEVELOPMENT THERE'S A LOT OF DISCONTINUITIY, MAY DO IT FOR SHORT PERIODS AND EPISODES OF HEAVY USE FLUCTUATION. >> THERE WILL BE A PARENTAL COMPONENT TRAINING IN THESE CLUSTERS? >> SO I'M NOT QUITE SURE I FULLY UNDERSTAND THE QUESTION, BUT LET ME TAKE A STEP BACK AND SAY THAT I THINK THAT THE KIND OF INFORMATION THAT ABCD AND NCANDA ARE PRODUCING HAVE TREMENDOUS OPPORTUNITIES FOR PREVENTION AND EDUCATIONAL MATERIALS FOR PARENTS, AS WELL AS FOR SCHOOLS, BOTH TEACHERS AND COUNSELORS. SO, FOR EXAMPLE, IF YOU HAVE YOUTH WHO ARE STILL EXHIBITING NEUROCOGNITIVE DIFFERENCES AS A RESULT OF THEIR BINGE DRINKING, TWO OR THREE WEEKS BEFORE, AND THEY ARE IN CLASSROOMS AND NOT PERFORMING AS WELL, I THINK THAT KIND OF INFORMATION CAN BE REALLY USEFUL FOR TEACHERS TO KNOW, IF YOU WANT TO DO YOUR BEST ON THIS, ON THE UPCOMING TEST, YOU NEED TO BE SURE THAT YOU'RE REMAINING ABSTINENT. I THINK STUDENTS DO THIS NATURALLY, STUDENTS HAVE HAD IN THEIR GRADES DO THIS NATURALLY BUT I THINK THERE WILL BE TREMENDOUS OPPORTUNITY TO ENHANCE PREVENTION MATERIALS THAT WE'LL BE ABLE TO PROVIDE FOR TEACHERS, FOR SCHOOL COUNSELORS, FOR NURSES, AND HEALTH CARE PRACTITIONERS THAT WILL UNFOLD FROM THESE TYPES OF STUDIES. >> AND DID NCANDA AND DO NCANDA AND ABCD COLLECT DATA ON THE ADOLESCENT DIETS AND SUPPLEMENTAL INTAKES? >> EXCELLENT QUESTION. YOU KNOW, WE DID SO IN A RELATIVELY SIMPLISTIC FASHION INITIALLY, AND ARE ASSESSING DIET IN A SLIGHTLY MORE COMPREHENSIVE WAY NOW. BUT THIS IS A GOOD EXAMPLE OF AN AREA WHERE IT IS INCREDIBLY IMPORTANT IN TERMS OF UNDERSTANDING PHYSICAL HEALTH, MENTAL HEALTH, AND YOUTH FUNCTIONING THAT IS -- BUT CAN'T -- JUST ONE OF THOSE AREAS THAT CAN'T HAVE THAT IN DEPTH EVALUATION IN LARGE SCALE STUDIES LIKE THIS. SO THE VALUE OF PROGRAMS LIKE NCANDA AND ABCD ARE THAT THEY CAN PROVIDE ENOUGH INFORMATION THAT CAN POINT INVESTIGATORS IN THE RIGHT DIRECTION AND PERHAPS GUIDE MORE IN-DEPTH INVESTIGATIONS, BUT CANNOT ANSWER ALL OF THE QUESTIONS. AND I DO WANT TO EMPHASIZE THAT POINT. WHILE BOTH OF THESE PROJECTS TOUCH ON THE MAJOR DOMAINS OF YOUTH DEVELOPMENT, WE DO NOT GO INTO DEPTH IN ALL OF THOSE DOMAINS BUT WOULD HOPE YOU WOULD USE OUR DATA AS YOU DO THAT AS SCIENTISTS. >> FULTON CRUZ ASKS A BETTER WAY, THE SIMILAR QUESTION TO WHAT I ASKED, IMPACT RESILIENCY, ARE THERE PREEXISTING RESILIENCE FACTORS LIKE YOUR MENTION OF PREEXISTING RISK FACTORS? >> SO, FULTON, THAT'S AN INCREDIBLY IMPORTANT ISSUE. AND I WILL JUST SHARE A LITTLE EARLIER STUDY THAT I DID WHETHER WE LOOKED AT FLUCTUATIONS AND BINGE DRINKING OVER THE COURSE OF A SINGLE YEAR IN HIGH SCHOOL FOR ADOLESCENTS, AND TOOK ALL OF THE KNOWN RISK AND RESILIENCE FACTORS THAT WE HAD AND EVALUATED THE EXTENT TO WHICH THEY PREDICTED EITHER INCREASES IN DRINKING OVER THE COURSE OF THAT YEAR OR DECREASES IN DRINKING OVER THE COURSE OF THAT YEAR. AND WHAT WE FOUND IS THAT WE ARE MUCH BETTER AT BEING ABLE TO PREDICT THE ONSET AND PROGRESSION OF ALCOHOL INVOLVEMENT AND OTHER SUBSTANCE INVOLVEMENTS THAN THE RESOLUTION OR THE DIMINUTION OF THAT. AND I WOULD SAY THIS IS A KEY AREA FOR US TO FOCUS ON IN THE FUTURE. REALLY UNDERSTANDING HOW IS IT THAT YOUTH NATURALLY CHANGE THEIR BEHAVIOR BECAUSE THE MAJORITY DO, EVEN THOSE WHO REACH LEVELS OF ALCOHOL OR OTHER SUBSTANCE DEPENDENCE, MINORITY RESOLVES IN MID TO LATE 20s AND WE NEED TO UNDERSTAND HOW THAT PROCESS UNFOLDS. EXCELLENT QUESTION. >> NEXT ONE IS NOT A QUESTION BUT A COMMENT FROM YOUR FAMILY. SO MARTY, YOUR HUSBAND, AND YOUR SON, KATHLEEN YOUR DAUGHTER, SAY THE FOLLOWING. WE'RE SO PROUD OF YOU AND WANT TO WISH YOU A HUGE CONGRATULATIONS ON BEING RECOGNIZED TO YOUR DEDICATION TO RESEARCH ON SUBSTANCE ABUSE ON ADOLESCENT DEVELOPMENT. I COULDN'T SAY IT ANY BETTER THAN THAT SO WE AT NIAAA ARE PROUD OF YOU, SANDY. THAT WAS A REALLY NICE COMMENT. SO LOOKS LIKE THERE'S ONE MORE QUESTION AND WE MAY LET YOUR POOR VOICE REST. THIS IS FROM MOHAMMED ACBAR, IN THIS PANDEMIC CRISIS, A GOOD QUESTION, WHAT WILL HAPPEN TO THE INTEGRITY OF THE OVERALL DATA FROM NCANDA AND ABCD CONSORTIA? >> I THINK THAT'S A CRITICAL QUESTION. BY THE WAY, THANK YOU, FAMILY. I DO THINK THAT'S A VERY IMPORTANT QUESTION. WE HAVE TRANSITIONED AS I MENTIONED FROM FACE-TO-FACE IN-PERSON ASSESSMENTS TO BY AND LARGE VIRTUAL ASSESSMENTS. AND THAT MEANS THAT YOUTH ARE AT THEIR HOME, PARENTS ARE AT THEIR HOME, AND WE'VE GOT THEM ON THE SCREEN WATCHING THEM WHEN THEIR FILLING OUT OUR MATERIALS OR DOING COMPUTERIZED TESTS AND INTERVIEWS, ET CETERA. AND SO WE TAKE GREAT CARE TO EVALUATE CHANGES THAT MIGHT BE A FUNCTION OF THE METHODS OF DATA GATHERING THAT WE'RE USING. AND TO HELP SUSTAIN THE RELIABILITY OF THE STUDY AND INTEGRITY OF THE STUDY. I WILL SAY THIS PANDEMIC IS AN UNPRECEDENTED CHALLENGE FOR RESEARCH OF THIS TYPE. WE'RE STUDYING YOUTH ALL ACROSS THE UNITED STATES. AND IN DOING SO, MANY SITES EITHER FOR A SHORT TERM PERIOD OR FOR SUBSTANTIAL PERIOD OF TIME HAVE BEEN PROHIBITED FROM BRINGING YOUTH IN TO DO SOME OF THE TESTING AND EVALUATION THAT CAN ONLY BE DONE IN PERSON. THIS IS PARTICULARLY TRUE FOR NEUROIMAGING. ONLY, FOR EXAMPLE, AT UCSD A MONTH AND A HALF AGO WERE ABLE TO GENERATE A PROTOCOL TO MAINTAIN SAFETY FOR RESEARCH ASSISTANTS AND FAMILIES THAT COULD ALLOW THE FAMILIES TO COME IN AND COMPLETE THE NEUROIMAGING COMPONENT AND SOME OF THE NEUROCOGNITIVE TESTS, THAT CAN ONLY BE DONE IN PERSON. SO IT'S A TREMENDOUS CHALLENGE. AND I WILL SAY I HAVE BEEN REMARKABLY SURPRISED BY THE CREATIVITY AND RESILIENCE OF BOTH INVESTIGATORS ACROSS THESE TWO CONSORTIA, AND RESEARCH ASSISTANTS IN FIGURING OUT WAYS TO BE ABLE TO MAINTAIN SAFETY, VIA THINGS LIKE WEARING MASKS, MAINTAINING DISTANCE, HAVING CLOSE CONTACT FOR VERY BRIEF PERIODS OF TIME, ADDITIONAL FACE COVERINGS, PLASTIC PROTECTION, ET CETERA. BUT IT'S A TREMENDOUS CHALLENGE, AND I THINK THAT WITH EVERY UNPRECEDENTED CHALLENGES CREATES OPPORTUNITIES TO THINK CREATIVELY ABOUT GATHERING DATA WE'RE GATHERING. IF IN THE FUTURE THINGS LIKE THE NCANDA APP, MOBILE NCANDA APP WILL GIVE US GOOD MEASUREMENTS, YOUTH CAN DO THAT ON AN ONGOING BASIS, IT WILL MAKE OUR JOB OF ASSESSMENTS MUCH EASIER BUT THERE WILL ALWAYS BE SOME COMPONENTS THAT WHERE WE NEED TO BE WITH OUR SUBJECTS, WITH OUR PARTICIPANTS IN PERSON. AND IN THIS CASE, GIVEN THE SEVERITY OF THE POTENTIAL CONSEQUENCES, WE NEED TO BE SURE WE'RE SUPPORTING AND ASSISTING FAMILIES AND FEELING COMFORTABLE AS WELL. >> THANK YOU, SANDY. YOU'VE BEEN VERY INDULGENT LETTING US ASK SO MANY QUESTIONS. THE QUESTIONS HAVE BEEN OUTSTANDING. THE TALK WAS OUTSTANDING. I THINK IT'S BEEN A GREAT -- NOW WE'RE GOING ON AN HOUR AND 45 MINUTES. I'M GOING TO LET YOU GO. I THINK THAT IF INDIVIDUALS STILL HAVE QUESTIONS FOR YOU I'M SURE YOU'D BE HAPPY TO ANSWER FROM YOUR OWN OFFICIAL E-MAIL AT UCSD, THEY CAN ALSO WRITE US AT NIAAA AND WE'LL BE HAPPY TO FORWARD QUESTIONS TO YOU. MY STAFF TELLS ME A CERTIFICATE IS ON ITS WAY. SO EVEN THOUGH WE COULDN'T DO THIS IN PERSON, AND I LONG FOR THE DAY WE CAN ALL GET BACK TOGETHER AND SMILE, ELBOW BUMP OR WHATEVER IS GOING TO BE APPROPRIATE. I'M GOING TO SAY GOOD-BYE AND AGAIN CONGRATULATIONS AND THANK YOU AND WONDERFUL DAY FOR ALL OF US HERE AT NIAAA. AND FOR THESE WONDERFUL DEVELOPMENTAL PROGRAMS THAT ARE ONGOING AT NIH. >> THANK YOU, GEORGE. BYE. >> BYE. THANK YOU VERY MUCH FOR JOINING US. WE REALLY APPRECIATE IT.