Article Plus content for Kandel, et al. Note: Sentences marked in bold complement the text of the full article’s Method section. Auxiliary Materials 527 528 Sample The data are from The Transition to Nicotine Dependence (TND) study, a prospective 529 five-wave longitudinal household study of a multi-ethnic cohort of 1,039 6th-10th graders 530 selected from the Chicago Public Schools (CPS) and one of their parents. A two-stage design 531 was implemented to select the target sample for the follow-up. In Phase I (spring 2003), 15,763 532 students in grades 6-10 were sampled from 43 public schools in the CPS. The sample 533 (N=1,039) was designed to provide approximately equal numbers of adolescents among the 534 three major ethnic groups: non-Hispanic white (N=272), non-Hispanic African American 535 (N=343), and Hispanic (N=424). Because of the ethnic distribution in the CPS, largely 536 Hispanic schools were excluded and schools with large numbers of non-Hispanic white 537 students were oversampled. The resulting sample is representative of each racial/ethnic 538 group from the CPS, except for Hispanics from largely Hispanic high schools and whites 539 with Polish speaking parents. Schools were divided into eight segments and the survey 540 administration was staggered over four months. The survey completion rate was 83.1%. A 541 target sample of 1,236 youths was selected: 1,106 tobacco users who started to use tobacco in the 542 prior 12 months and 130 non-tobacco users susceptible of starting to smoke, divided among non- 543 Hispanic whites, non-Hispanic African Americans and Hispanics. Susceptible non-tobacco users 544 satisfied 2 of 3 criteria as per Pierce et al.41: (a) might try smoking a cigarette soon; (b) did not 545 answer “definitely not” to whether would smoke if a friend offered them a cigarette; or (c) will 546 be smoking cigarettes in one year. Sensitivity and specificity of these criteria for predicting 547 the onset of smoking among a sample of baseline adolescent never smokers four years later 1 548 were 66.7% and 61.9%, respectively.41 Non-tobacco users were included as targets in the 549 household sample so as to not have to indicate to parents that their child was a tobacco user when 550 requesting active parental consent for child participation. Whites and African Americans who 551 had started to use tobacco 0-12 months earlier and Hispanics who had started 0-6 months 552 earlier were selected with certainty; Hispanics who started 7-12 months earlier were 553 sampled at a 25% rate, because of the larger number of Hispanics than other race/ethnic 554 groups in the sample schools. The onset of tobacco use was based on a question that asked 555 students “How long has it been since you FIRST tried or used a tobacco product?” The 556 coded responses ranged from “I first tried within the last 3 months, 4-6 months ago, 7-12, 557 13-18, 19-24 and more than 24 months ago.” Of the tobacco users in the school survey 558 (N=4,363), 1,623 (37.2%) reported having started to use within the last 12 months; 1,106 559 were selected for the target sample. Another 751 (17.2%) reported having started 13-24 560 earlier and 1,989 (45.6%) started more than 24 months earlier. Youths who initiated 561 tobacco use within the last 12 months or 13-24 months earlier were older at onset and 562 lighter users than those who initiated tobacco use more than 24 months earlier. At onset, 563 those who initiated tobacco use within the last 12 months were on average 12.2 years old 564 (S.D.=2.1), those who initiated 13-24 months earlier were 12.3 years old (S.D.=1.8), and 565 those who initiated 24 months earlier were 10.7 years old (S.D.=2.0). Of these three groups, 566 13.6%, 19.2% and 25.2%, respectively, had ever smoked more than 25 cigarettes. 567 In Phase II, on average 9 weeks after each school survey, 1,039 youths (84.1% of 1,236 568 target) (272 white, 343 African American, 424 Hispanic) and one parent (86.8% mothers) 569 participated in the two year (2003-2005) longitudinal follow-up consisting of three annual 90 570 minute computerized household interviews with youths and parents (W1, W3, W5), and two 20 571 minute bi-annual interviews with youths six months after W1 and W3 (W2, W4). Of the 1,039 572 youths, 922 were tobacco users (832 smokers); and 117 were non-tobacco users susceptible of 2 573 starting to smoke. Completion rates at W2-W5 were 96.0% of the W1 sample. The National 574 Opinion Research Center (NORC), at the University of Chicago, conducted the fieldwork. In 575 902 (86.8%) families, mothers were the participating parent (870 biological, 21 adoptive, 11 576 step or foster); 58 respondents were fathers; 79 were other parental figures, such as 577 grandmothers. Hispanics who had started to use tobacco 7-12 months earlier were given a 578 weight of 4, since they were sampled at the rate of 25%. All Hispanic tobacco users were 579 rescaled to the unweighted number who were interviewed. 580 Human subject procedures 581 Passive parental consent was obtained for the school survey and active consent for the 582 household interviews; adolescent assent was obtained for both administrations. Interviewers 583 emphasized that all answers would be confidential. All procedures were approved by the 584 Institutional Review Boards of the New York State Psychiatric Institute, Columbia University, 585 and NORC. 586 Data collection: Overview 587 Selected DSM-IV child psychiatric disorders were ascertained at W1, W3 and W5 from 588 youths and mothers. Youths reported at every wave about their smoking, other tobacco use and 589 DSM-IV nicotine dependence symptoms, and annually about their use and DSM-IV abuse and 590 dependence symptoms for other substances, novelty seeking, and exposure to smoking siblings 591 and peers. Mothers reported annually on their smoking, DSM-IV nicotine dependence 592 symptoms, DSM-IV depression, and delinquency. 593 Definitions of variables 594 Variables were measured from youths (Y), and from parents (P) about themselves or the 595 youths. Predictor variables were measured by W3, outcome variables by W5. The highest 596 values reported by each time period was selected. 3 597 (Y-P) Psychiatric disorders: Measured by the NIMH Diagnostic Interview Schedule for 598 Children (DISC-IV-Y and -P).42 Mood disorders (major depressive disorder (MDD) and 599 dysthymia (DYS) were assessed at W1, W3 and W5; anxiety disorders (social phobia, panic, 600 generalized anxiety, post-traumatic stress (PTSD)), and disruptive behavior disorders (attention- 601 deficit hyperactivity (ADHD), oppositional defiant (ODD), conduct disorder (CD)) at W3 and 602 W5. Each disorder was ascertained from parents and youths, except ADHD (parents only). For 603 each disorder, lifetime and last 12 month symptoms were asked at the first assessment; last 12 604 months symptoms were asked at subsequent assessments. For DYS and PTSD, only last 12 605 month symptoms were asked at all assessments. Scoring that combined criteria from parent and 606 child reports without impairment was used.43 Due to human subjects concerns, questions 607 about current suicidal ideation and prior suicide attempt were removed from W1 major 608 depressive disorder (MDD), and forced sex from CD. The suicide-related items were 609 reinstated at W3 and W5, when a clinical psychologist was available to provide a mental 610 health consultation, if needed. The diagnostic scoring was modified slightly for MDD at 611 W1 and was based on meeting 4 of 8 rather than 5 of 9 criteria. The modified definition 612 yielded a slightly higher rate of last 12 month MDD (4.5%) than the standard definition 613 used at W3 (3.3%). Thus, the mood disorder variable based on the modified W1 MDD 614 definition may yield a slightly higher rate of disorder than the standard definition. The 615 scoring for CD was not modified and meeting 3 of 15 criteria was retained (Dr. Prudence 616 Fisher, personal communication, 10/31/07). 617 (Y-P) Onset ages of psychiatric disorders: (Not available for PTSD). The earliest age reported 618 by parent or youth for a specific disorder defined onset age for the class. Onset age for CD is 619 not ascertained for the diagnosis but rather for each positive symptom. Thus, for youths 620 who met diagnostic criteria for CD, the earliest age of a positive symptom determined the 621 onset age for the disorder. 4 622 (Y) Nicotine dependence: Measured as per the Diagnostic and Statistical Manual of Mental 623 Disorder (DSM-IV)44 by an instrument developed for adolescents.45 The 11-item scale measured 624 symptoms in the last 12 months that define the seven DSM-IV dependence criteria:44 tolerance, 625 withdrawal, impaired control, unsuccessful attempts to quit, great deal of time spent using, 626 neglect important activities, and use despite physical or psychological problems (α=.85). For 627 the measurement of the seven DSM-IV dependence criteria, four criteria were indexed by 628 two alternate symptoms and three were indexed by a single symptom. The criteria of 629 withdrawal asked about 12 specific symptoms; 3 were sham items included to check the 630 reliability of responses. These 3 items and a fourth item about craving were excluded from 631 the scoring of withdrawal (α=.92). The withdrawal criterion was met when respondents 632 reported at least 4 of the 8 valid symptoms. Full dependence was defined when 3 criteria were 633 met. 634 (Y) Onset age of first nicotine dependence criterion: Month/year of first criterion minus birth 635 date. 636 (Y) Onset age of full nicotine dependence: Month/year of third criterion minus birth date. 637 (Y) Onset age of cigarette use: Month/year first used cigarettes minus birth date. 638 (Y) Initial sensitivity first tobacco use:46 Experiences associated with first tobacco use. Two 639 scales averaged the scores of component items: pleasant symptoms (pleasant sensations, 640 relaxation, pleasurable dizziness, pleasurable rush/buzz (α=.71)); unpleasant symptoms 641 (unpleasant sensations, nausea, unpleasurable dizziness, unpleasurable rush/buzz, coughing, 642 heart pounding, headache, bad taste (α=.78)). Each symptom coded 1=none to 4=intense 643 experience. 644 (Y) Lifetime smoking: At W1, ever smoked a cigarette, even a puff; at subsequent waves, 645 smoked since the prior interview. 5 646 (Y) Number cigarettes smoked lifetime: Recoded to mid-point: smoked one or more puffs but 647 never a whole cigarette=.5; 1 cigarette=1; 2-5 cigarettes=3; 6-15=10; 16-25=20; 26-99=62; and 648 100+=100 cigarettes 649 (Y) Other tobacco use lifetime (smokeless, cigars, pipes, bidis, kreteks). 650 (Y) Alcohol use and abuse/dependence lifetime: Combined ever used and DSM-IV abuse or 651 dependence on alcohol, ascertained by the DISC-IV-Y: never used alcohol; used but no 652 abuse/dependence; lifetime alcohol abuse/dependence. 653 (Y) Alcohol, marijuana and other illicit substance use and abuse/dependence lifetime: 654 Combined ever used and DSM-IV abuse or dependence on alcohol, marijuana or any other illicit 655 drug (OID), ascertained by the DISC-IV-Y: never used alcohol, marijuana or OID; used but no 656 abuse/dependence; lifetime alcohol, marijuana or OID abuse/dependence. 657 (Y) Perceived peer smoking: At least one friend currently smoked. 658 (Y) Perceived siblings’ smoking: Sibling ever smoked. 659 (P) Parent smoking/nicotine dependence lifetime: Combined ever smoked and DSM-IV nicotine 660 dependence, measured by the same scale as for the youths (α=.80): never smoked; smoked but 661 no dependence; lifetime nicotine dependence. 662 (P) Parent lifetime depression: DSM-IV major depressive disorder as per the Composite 663 International Diagnostic Interview (CIDI 2.1). 664 (P) Parent lifetime delinquency: Count of 11 delinquent activities (range 0-11; α=.89): 665 damaging property, injuring persons, shoplifting, stealing something worth < or > $50, 666 breaking into house/building, threatening with weapon, fighting with another/group, 667 driving car without owner’s permission, and getting into trouble with police. Scored 668 highest value at W1 or W3. 669 (Y) Youth novelty seeking: Based on Cloninger’s Tridimensional Personality Questionnaire.47 670 Average of 9 five-point items (α=0.80): try things for fun, look for something exciting, can 6 671 get people to believe lies, do things based on how feel at the moment, get excited and lose 672 control, like when people do whatever they want, follow instincts, can stretch the truth and 673 change interests a lot. The response alternatives were 1=not at all true; 2=a little true; 674 3=somewhat true; 4=pretty true; 5=very true. Scored highest value at W1 or W3. 675 (Y) Age: in years. 676 (Y) Race/ethnicity: non-Hispanic white; non-Hispanic African American; Hispanic. 677 (Y) Gender 678 Participants and non-participants in household interviews 679 Participants (N=1,039) and non-participants (N=197) in the household interviews 680 were compared on sociodemographic characteristics and school reports of smoking and 681 depressive symptoms. Non-participants did not differ on age or gender; however, a higher 682 proportion of non-Hispanic whites than non-Hispanic African Americans declined to 683 participate. Non-participants were more likely than participants to report having ever 684 smoked (92.8% vs. 85.0%, p<0.01), having smoked more extensively (11.1% versus 6.3% 685 had ever smoked 100 or more cigarettes, p<0.05), and having met criteria for DSM-IV 686 nicotine dependence (31.1% versus 24.4%), although this difference was not statistically 687 significant. Non-participants did not differ from participants on depressive symptoms. 688 Inconsistencies in reporting of tobacco use 689 There were discrepancies between the school and household reports of tobacco 690 use.56 Of the youths who had reported any tobacco use in school (N=922), 213 denied at the 691 Wave 1 household interview having ever used tobacco; of those who reported in school 692 smoking cigarettes (N=832), 189 denied having ever smoked at Wave 1. There were 693 further discrepancies in the age of tobacco use onset. In the household interviews, 694 adolescents were asked the specific date (month, year) of first use of each tobacco product 695 ever used. Time since onset was calculated as the difference between the earliest date of 7 696 use of any product and the interview date. Only 281 (39.6%) of the 709 adolescents who 697 had reported in school having started using tobacco in the prior 12 months were identified 698 as having started to use within the prior year based on the more precise (month/year of 699 onset) ascertainment in the household interviews; 428 were estimated to have started to 700 smoke more than one year before Wave 1. Of these, 75 started within 12 months prior to 701 the school survey but more than 12 months prior to the household interview because of the 702 time lag between the two data collections. Those who denied having used tobacco in the 703 household interviews were, according to their school reports, younger, more likely to be 704 African Americans, lighter smokers and less likely to meet criteria for the full DSM 705 dependence syndrome than those who admitted use in the household. The youths (N=353), 706 who in the household were estimated to have started using tobacco more than a year prior 707 to the household interview even though they had been selected because they had reported 708 in the school having started to use tobacco within the prior 12 months, were more likely to 709 be males, African Americans, heavier smokers and to have experienced more DSM-IV 710 dependence symptoms than those who were correctly assessed as having started using 711 tobacco within the prior 12 months. The group (N=75) who no longer fell within the 12 712 month interval because of the time lag between the school and household data collections 713 did not differ from those correctly classified. Thus, those who denied having used tobacco 714 in the household were lighter users than those who admitted use. By contrast, those who 715 were reclassified as having started to use more than 12 months earlier were heavier users 716 than those who remained classified as having started within the last 12 months. The 717 cumulative impact of non-participation and inconsistent reporting resulted in a sample that 718 was biased towards the exclusion of tobacco users, especially heavier users. 719 Analytical samples for current study 8 720 Five analytical samples were defined as of W3: (1) Total cross-sectional sample 721 (N=1,039) to provide background descriptive information about the prevalence of smoking, 722 nicotine dependence, and psychiatric disorders in the cohort; (2) longitudinal sample of lifetime 723 smokers without nicotine dependence symptoms as of W3 (N=419) to examine psychiatric 724 disorders as predictors of the onset of nicotine dependence by W5; (3-5) three longitudinal 725 samples of lifetime smokers without a lifetime diagnosis of an anxiety (N=686), mood (N=636), 726 or disruptive (N=580) disorder as of W3 to examine nicotine dependence as a predictor of the 727 onset of each psychiatric disorder by W5. 728 Statistical analysis 729 Logistic regressions were estimated to identify the prospective associations between (1) 730 psychiatric disorders and onset of nicotine dependence, and (2) nicotine dependence and onset of 731 psychiatric disorders. The outcome variable for onset of dependence was meeting at least one 732 criterion by W5. The three outcome variables for onset of psychiatric disorders by W5 were 733 meeting last 12 month DSM-IV criteria for any anxiety, mood, or disruptive disorder, 734 respectively. Multivariate analyses controlled for comorbidity among psychiatric disorders; 735 smoking history (age of smoking onset, initial sensitivity to tobacco, quantity smoked lifetime, 736 other tobacco use lifetime); other substance use (alcohol, marijuana and OID use and 737 abuse/dependence); peer and sibling smoking; novelty seeking; parental nicotine dependence, 738 depression and delinquency. To the extent possible, identical covariates were included across all 739 models. Smoking history covariates were included in models predicting psychiatric disorder 740 since they may have unique effects over those of dependence. Selected two-way interaction 741 effects were tested to examine if the impact of predictors for each outcome were moderated by 742 gender or race/ethnicity. All analyses were weighted and conducted in SAS® V9.1. 743 744 To control for Type I errors in univariate analyses, the Holm’s procedure48, a modified Bonferroni approach, was applied to conceptually related groups of variables. Groups of 9 745 variables for Table 1 included: (1) anxiety disorders (social phobia, panic, generalized 746 anxiety, post-traumatic stress, any anxiety); (2) mood disorders (major depression, 747 dysthymia, any mood); (3) disruptive disorders (attention deficit, oppositional defiant, 748 conduct, any disruptive); and (4) smoking/dependence (ever smoked, and 1+ and 3+ nicotine 749 dependence criteria); and for Tables 2 and 3 (1) sociodemographics (age, gender, 750 race/ethnicity); (2) psychiatric disorders (anxiety, mood, disruptive), smoking/tobacco 751 history (onset age of smoking, initial positive and negative sensitivity to tobacco, quantity 752 smoked, other tobacco use, and nicotine dependence (for Table 3 only), exposure to 753 smoking in the proximate social environment (peer, sibling, parental smoking), parental 754 psychopathology (depression and delinquency). Three variables, any psychiatric disorder 755 (Tables 1-2), alcohol, marijuana or OID use and abuse/dependence and novelty seeking 756 (Tables 2-3) were treated individually. For each main effect, the p values for each group of 757 variables were ordered from smallest to largest. The p value was compared to the 758 significance level .05/(k - i + 1), where k = the number of main effects tested in each 759 variable grouping, and for k main effects, i = 1,2,…, k. For example, in Table 1, for anxiety 760 disorder, five main effects for gender were tested. Post traumatic stress was accepted 761 because its p value was less than .05/(5 - 1 + 1) = .01, and any anxiety disorder because its p 762 value was less than .05/(5 – 2 + 1)=.0125. 763 Appendix Table A presents the distributions of covariates for the four longitudinal samples. 10