VYTP Virginia Youth Tobacco Project

1. VYTPVirginia Youth Tobacco Project Securing the health of Virginia’s youth through science

2. VYTPVirginia Youth Tobacco Project Report to The Virginia Tobacco Settlement Foundation Board of Trustees Research Committee 18 March 2003

3. VIRGINIA YOUTHTOBACCO PROJECT COALITION BUILDING Robert L. Balster, PhD

4. Goals • Build statewide trans-disciplinary program of research on causes and prevention of youth tobacco use • Attract faculty scholars to work on problems of youth smoking • Use VTSF funding as base for attracting additional outside funding for youth tobacco research in Virginia

5. Implementation Methods • Solicited input from members of the Virginia Research Consortium (VPRs) • Utilized our knowledge of tobacco experts in Virginia • Identified a contact individual at each institution to be included in the first round • Obtained proposals from these project PIs • Funded four subcontracts in August 2002 • Hired project director (Randy Koch) in February 2003

6. VYTP Coalition:Current Components • GMU (Robert Smith, PI) • JMU (Steve Evans, PI) • UVA (Richard Bonnie, PI) • Virginia Tech (Peggy Meszaros, PI) • VCU (Roy Pickens and Bob Balster, PIs)

7. GMU Component: Robert Smith, PIAnimal Model of Adolescent Nicotine Effects • Does peri-adolescent nicotine exposure cause lasting cognitive changes? • Does peri-adolescent nicotine contribute to increased effort to self administer cocaine? • How does peri-adolescent nicotine affect gene expression, evaluating all genes? Received separate funding from VTSF

8. JMU Component: Steven Evans, PITobacco Prevention Research Center • Subcontract with VCU supports three separate projects that address risk factors and develop interventions for preventing and stopping tobacco use • Youth with ADHD (Steven Evans) • Dieting behavior & weight concerns among adolescents (Monica Reiss-Bergan) • Smoking cessation using alternative and complimentary health practices (Cheryl Talley & Charles Lockett) • Also received separate funding from VTSF for clinical trial work

9. UVA Component: Richard Bonnie, PIYouth-Centered Tobacco Policy Research • Assembled investigative team • Richard Bonnie - health policy and ethics • Michael Moore – health economics • Pam Kulbock – adolescent health • Marian Moore – marketing and communications • Gerald Clore – social psychology • Victor Bovbjerg – epidemiology • Ruth Gaare Bernheim – policy studies • Established bi-weekly tobacco research colloquium

10. UVA ComponentYouth-Centered Tobacco Policy Research • Projects Underway • Econometric studies of effects of policy interventions on dynamics of youth smoking and on low birthweight • Study of deterrent effect of youth access restrictions and their enforcement on retailers • Analysis of NAAG MSA Enforcement

11. UVA ComponentYouth-Centered Tobacco Policy Research • Projects in conception and development • Emotional reactions to tobacco advertising and counter-advertising • Relationship between attributions and cessation outcomes • Effects of threatened sanctions for underage tobacco and alcohol use • Conceptual and operational development of policy-relevant influences on non-smoking behavior by young teens

12. Virginia Tech Component: Peggy Meszaros, PIAdolescent Female Smoking • Secondary analysis of data on Virginia youth from two surveys • Identify risk and protective factors • Evaluate quitting strategies for female smokers • Disseminate information on effective interventions

13. VIRGINIA YOUTHTOBACCO PROJECT INTEGRATED RESEARCH AND EVALUATION AT VCU Roy W. Pickens, PhD

14. Susceptibility to Nicotine Dependence: A Complex Developmental Process • Varies with inherited characteristics of individuals • Varies with the age of users • Depends to some extent on environmental influences, from parents, peers, and the media • Manifested in various stages of use behavior

15. Stages of Development in Adolescent Smoking Behavior: Points of Focus for Research and Intervention Stage 1 Stage 2 Stage 3 Stage 4 Stage 5 CONTEMPLATING TRYING EXPERIMENTING Relative Numbers of Adolescents/Stage* USING REGULARLY USING HEAVILY Increasing Risk of Nicotine Dependency * Estimates, based on CDC, “Trends in Cigarette Smoking Among High School Students – United States, 1991-2001,” MMRW 51(19).

16. Current VCU ResearchProject Themes • Genetic Influence over Tobacco Use in Adolescents • How These Genetic Influences are Expressed in Nicotine Pharmacology • Clinical Trials in Preventing Adolescents’ Initial Tobacco Use from Progressing to Nicotine Dependency • Evaluation of Community- and School-Based Youth Anti-Tobacco Programs

17. Smoking is Highly Heritable Non-shared Environment Shared Environment Shared Environment Genes Genes Non-shared Environment Smoking Initiation Smoking Persistence Data presented include females only; males similar.

18. Approaches to the Study of Genetic Influence over Tobacco Use and Nicotine Dependency • Genetic Epidemiology: twin studies to determine the role of genetic and environmental influences at each stage of tobacco use • Gene Mapping: the use of epidemiological data to identify suspect chromosomal regions • Candidate Gene Studies: identification of genes in these chromosomal regions suspected to be associated with tobacco use • Gene Activation Studies: laboratory investigation of gene expression using animal models

19. Project 1. Genetic Epidemiology: Genetic Factors in the Transition Through Smoking Stages • Donna Miles, PhD (PI) • Roy Pickens, PhD • Lindon Eaves, PhD DSc • Judy Silberg, PhD

20. Goals • Examine genetic and environmental factors that play a role in the transition between smoking stages • Identify common (shared) and unique genetic and environmental influences at each stage of smoking

21. Twin Research

22. Longitudinal Twin Study • At VCU we maintain large twin registries, under the management of the Mid-Atlantic Twin Registry (MATR) • We are now conducting an adolescent behavioral-development study on 1412 twin pairs • Subjects first interviewed in adolescence (ages 8-16 years old) • Currently re-interviewing these twins, who are now in young adulthood (ages 20-28 years)

23. Longitudinal Twin Study: Progress to Date • Secured MATR approval • Secured IRB approval • Obtained NIH Certificate of Confidentiality • Developed telephone interview, which uses Optiscan technology • Completed hiring and training telephone interviewers • Conducted preliminary data analysis on adolescent sample

24. Tobacco Use among Twins # twins ages Wave I Current study (completed) (expected)

25. Future Directions in Twin Research at VCU • December 2002, submitted NIH grant application entitled “Child Psychopathology-Adult SUD Longitudinal Twin Study” • Extends work begun with VTSF funding • Based on methods used in VTSF-funded project • 4 year project • Total cost, $2,003,614

26. Project 2. Gene Mapping and the Search for Candidate Genes: What gene groups are involved in nicotine dependence? • Kenneth Kendler, MD (PI) • Xiangning Chen, PhD

27. Goals • Identify genetic loci related to adolescent tobacco use, through gene association studies • Investigators have previously identified chromosomal regions associated with tobacco use in adults • Are these same regions associated with smoking initiation and dependence in adolescents?

28. Genome Scan of Adult Smokers

29. Progress in Genetic Mapping and Candidate Gene Project • Completed analysis of about 2/3 of chromosomal data from samples of adolescents in Christchurch, New Zealand and Richmond, Virginia • Identified several candidate genes that may be involved in susceptibility to tobacco-use initiation and nicotine dependency • Established collaboration with researchers in pharmacology to analyze candidate gene expression in laboratory animals

30. Project 3. Gene Expression in Adolescents • Billy Martin, PhD (PI) • Imad Damaj, PhD • Michael Miles, PhD • Jenny Wiley, PhD

31. Goal • Determine the mechanisms by which gene expression influences adolescent susceptibility to nicotine

32. Nicotine Sensitivity, Dependence, and Metabolism in Adolescent Mice Genetic Influences Acute Sensitivity Metabolism & Pharmacokinetics Tolerance & Dependence

33. Models for Acute Sensitivity to Nicotine In Vivo Effects In Vitro Effects Body Temperature Locomotor Activity Analgesia 3H-Nicotine Binding: α4β2 Subtype 3H-MLA Binding: α7 Subtype Seizures Anxiolytic Effect Nicotinic Antagonists

34. Assessing Nicotine Dependence Liability Physical Dependence Positive Reinforcement Tolerance Somatic & Affective Withdrawal Signs Acute Chronic Conditioned Place-Preference

35. Enzymes for Nicotine Metabolism Differ in Early Adolescent and Young Adult Mice –Sensitivity to Nicotine is Likely Age Dependent <35 day 56 day Early Adolescent Young Adult

36. Determining the Genetic andBio-behavioral Bases forAdolescent Responses to Nicotine • Collaboration between Projects 2 & 3: NIH Center Grant proposal now in development to tie together human and animal research • Quantitative Trait Loci (QTL) methodology • Search for genes that determine age and stage differences in sensitivity, dependence, and metabolism

37. Project 4. Preventing Initial Tobacco Use from Progressing to Nicotine Dependency • Thomas Eissenberg, PhD (PI) • Deborah Haller, PhD • Michelle Acosta, PhD

38. Goals • Understand in detail the stages of youth smoking behavior, through clinical laboratory assessment of individual adolescents’ responses to smoking • Using clinical-assessment and follow-up interview data, test various interventions for their effectiveness in preventing adolescent progression to nicotine dependency

39. Subjects • Adolescent smokers: 12-18 years of age • Stage 3 (experimenting) smokers: users who report smoking more than 1 cigarette per month but less than 1 per day • Stage 4 (regular) smokers: users who report smoking more than 1 but less than 10 cigarettes per day

40. Clinical Assessment: Testing Adolescents’ Responses to Smoking • Physiological measurements, before and after one cigarette • heart rate • breath CO • saliva cotinine (nicotine metabolite) • saliva cortisol (stress hormone) • puff topography • Craving and withdrawal questionnaires, before and after one cigarette

41. Clinical Intervention: Testing Various Means to Prevent Adolescents from Progressing to Dependency • Compare the success rates of different intervention modes in preventing subjects’ stage progression after 1, 3, 6, 9, and 12 months • Intervention 1: Motivational interviews, providing subjects with personalized information and clinical-assessment feedback on the consequences of smoking • Intervention 2: Anti-tobacco video material • Intervention 3: Anti-tobacco print material

42. Progress in Clinical Trials Project • IRB approval of protocol has been granted • Clinical assessments pilot tested • Interventions prepared and pilot tested • Subject recruitment to begin in April 2003

43. Project 5. Youth Tobacco Evaluation Project (YTEP) Project Team: Ilene Speizer, Brian Smith, Diane Baer Wilson, Melanie Bean, Karen Mitchell, Samy Uguy, Panumas Assavarakpreecha, Ramesh Ramakrishnan, Joyce Phillips, and Elizabeth Fries (PI)

44. Objectives of YTEP • Design a comprehensive evaluation of the 109 youth tobacco prevention programs funded by the Virginia Tobacco Settlement Foundation • Train grantees to implement appropriate evaluation components for their programs • Provide evaluation assistance for grantees • Provide analysis and dissemination of findings

45. Single session programs Multiple session programs

47. Overall Evaluation Design • Process Evaluation • All programs • Session logs – content and delivery • Instructor survey – acceptability of program to instructors and participants • Pre K – 3rd grades: Parent survey – determine if kids understood and discussed program • 4th & 5th grades: Brief participant survey – perspectives on content, delivery, and appropriateness • Parent and family programs: Participant survey– content, delivery, and appropriateness

48. Overall Evaluation Design, cont. • Outcome Evaluation • 6th – 12th grades (76 of 109 grantees doing outcome evaluation) • Pre-test survey: obtain baseline tobacco use • Post-test survey: examine changes between pre- and post-tests • Parental notification prior to 1st survey • No identifying information kept on record • Match pre- and post-tests with anonymous linking scheme • Participants complete survey and place in an envelope and seal envelope

49. Design of Outcome EvaluationGrades 6 to 12 Pre-test Post-test 1-year Follow-up Funded Program Note: Given limitations of pre-post design, where ever possible we will collect 1 year follow-up. All data are linked due to sampling/generalizability limitations. Grantees receiving multiple years of funding will also be followed for 2-6 years depending on the age of the child.

50. Framework: Outcome Questionnaire Development • PERSONAL • Knowledge of consequences • Functional meanings • Subjective expected utility • SOCIO-DEMOGRAPHIC • Age • Low SES • Developmental stage • Gender • Self esteem • Self efficacy • Self image • ENVIRONMENTAL • Accessibility • Advertising SMOKING STAGE Preparatory  Trying  Experimental  Regular Use  Addiction • Personality • Psychological well-being • Parental use • Sibling use • Parental supervision and strictness • BEHAVIORAL • Academic achievement • Participation in sport & healthy behaviors • Peer use • Social bonding • Normative expectations • Peer groups • Other adv. behaviors (risk-taking) • Behavioral skills