Awake whole-brain functional connectivity alterations in the adolescent spontaneously hypertensive rat feature visual streams and striatal networks.

Brain mechanisms underpinning attention deficit/hyperactivity disorder (ADHD) are incompletely understood. The adolescent spontaneously hypertensive rat (SHR) is a widely studied preclinical model that expresses several of the key behavioral features associated with ADHD. Yet, little is known about large-scale functional connectivity patterns in the SHR, and their potential similarity to those of humans with ADHD. Using an approach comparable to human studies, magnetic resonance imaging in the awake animal was performed to identify whole-brain intrinsic neural connectivity patterns. An independent components analysis of resting-state functional connectivity demonstrated many common components between the SHR and both Wistar Kyoto and Sprague-Dawley control strains, but there was a divergence in other networks. In the SHR, three functional networks involving the striatum had only weak correlations with networks in the two control strains. Conversely, networks involving the visual cortex that was present in both control strains had only weak correlations with networks in the SHR. The implication is that the patterns of brain activity differ between the SHR and the other strains, suggesting that brain connectivity patterns in this animal model of ADHD may provide insights into the neural basis of ADHD. Brain connectivity patterns might also serve to identify brain circuits that could be targeted for the manipulation and evaluation of potential therapeutic options.

The federal initiative to halt the sale of tobacco to children--the Synar Amendment, 1992-2000: lessons learned.

BACKGROUND: The Synar Amendment was enacted by the US Congress in 1992 to require states and territories to establish and enforce laws prohibiting the sale of tobacco to minors. OBJECTIVE: To describe state and federal efforts to comply with the Synar mandate. METHODS: State and federal actions were examined for the eight years following enactment. DATA SOURCES: Federal documents from 1992-2003, annual block grant applications from 59 states and territories describing activities during federal fiscal years 1995-2000. MEASURES: Whether applicants made a good faith effort to comply by enacting a law, enforcing it with inspections and penalties, conducting a valid survey and meeting violation rate targets set by the Department of Health and Human Services (DHHS). RESULTS: Between 1996 and 2000, 26 states had made a good faith effort to comply with Synar every year. In 2000, 57 jurisdictions (excluding Maryland and Montana) had established laws without loopholes, 57 conducted a valid survey, and 54 actively enforced their laws. By 2002, violation rates had dropped substantially everywhere but Alaska and a few small territories. No state reached the violation rate goal of 20% without penalising violators. CONCLUSIONS: The Synar Amendment has resulted in the universal adoption of laws prohibiting tobacco sales to minors and almost universal enforcement of those laws, resulting in dramatically reduced violation rates. Implementation was slowed significantly by a lack of good faith effort in many states and by DHHS's decision not to require states to enforce their laws by penalising lawbreakers.

Genetically decreased CYP2A6 and the risk of tobacco dependence: a prospective study of novice smokers.

OBJECTIVE: Case control studies in adults suggest that defective alleles in the gene that codes for the hepatic cytochrome P450 2A6 (CYP2A6) protect against nicotine dependence (ND) and higher levels of cigarette consumption. These two hypotheses were tested in young adolescents. DESIGN: Self reports of tobacco use and ND symptoms were collected every 3-4 months in a prospective study of 1293 grade 7 students from a convenience sample of 10 schools. SUBJECTS: 281 smokers with genetic data were analysed; those who were not already tobacco dependent and who had inhaled (n = 228) were followed 29.9 months on average, until they became dependent or were censored. MAIN OUTCOME MEASURES: The association between metabolic activity, represented by CYP2A6 genotype, and conversion to dependence was analysed using Cox's proportional hazards model. RESULTS: During follow up 67 subjects (29.4%) became dependent. Relative to CYP2A6*1/*1, having 1-2 copies of the inactive CYP2A6*2 or *4 variant was a strong risk factor for developing dependence (hazard ratio 2.8, 95% confidence 1.3 to 6.3). Subjects with 1-2 partially inactive CYP2A6*9 or *12 variants were not at increased risk. Mean past-week cigarette consumption at the end of follow up (controlling for age, sex, and number of months since first inhalation) among dependent subjects was 29.1 among normal inactivators, compared to 17.2, and 12.7 among slower (1-2 copies of *9 or *12), and slowest (1-2 copies of *2 or *4) inactivators, respectively (p = 0.09). CONCLUSION: Adolescents with 1-2 copies of CYP2A6*2 or *4 are at substantially increased risk of becoming dependent but smoke less once dependent. Genetic risk for ND may need to be considered in the conceptualisation of tobacco control programmes for adolescents.

Short term patterns of early smoking acquisition.

OBJECTIVE: To describe short term patterns of smoking acquisition exhibited by adolescent smokers. DESIGN: Interview records from the prospective development and assessment of nicotine dependence in youth study were examined retrospectively. Interviews were conducted three times per year over 30 months. SUBJECTS: 164 students in grades 7-9 (ages 12-15 years, 86 girls, 78 boys) who had used cigarettes at least twice. MAIN OUTCOME MEASURES: A continuous timeline of smoking activity, beginning with the subject's first use of tobacco and continuing through follow up, was translated into six patterns--abstinent, sporadic, occasional, daily, escalating, and intermittent. Outcome measures were the proportion of subjects starting/ending in each pattern, and the number of transitions per subject between patterns. RESULTS: There was a general but discontinuous progression from infrequent to more frequent use, with many interspersed periods of not smoking. Escalation to daily smoking was common after the development of dependence symptoms, but was rare among those who did not have symptoms. After the appearance of symptoms, both transitions to heavier daily smoking and attempts at cessation increased. CONCLUSIONS: Movement to heavier, more frequent smoking is generally unidirectional, although many youths attempt to quit one or more times. The appearance of any symptom of dependence altered the subsequent pattern of smoking behaviour. Future investigators might consider using more frequent data points and a continuous timeline to track smoking behaviour.

Assessment of nicotine dependence symptoms in adolescents: a comparison of five indicators.

OBJECTIVE: To examine the psychometric properties, test-retest reliability, and convergent construct validity of five indicators of nicotine dependence (ND) symptoms in adolescents. DESIGN: Analysis of baseline data from a prospective study on the natural history of ND in 1264 adolescents aged 12-13 years. SETTING: Ten Montreal high schools. SUBJECTS: 233 grade 7 students who had smoked cigarettes one or more times in the three months preceding the baseline data collection. MAIN OUTCOME MEASURES: Five indicators of ND symptoms including two that are multi-dimensional (a proxy measure of ICD-10 criteria for tobacco dependence; the Hooked on Nicotine Checklist (HONC)) and three new indicators of "symptom clusters" that emerged from principal component analysis (ND/cravings, withdrawal symptoms, self medication). RESULTS: All five indicators demonstrated acceptable internal and test-retest reliability. The correlation between the HONC and ND/cravings was 0.910. All other correlations between indicators ranged between 0.716-0.824. There was considerable overlap in the independent correlates identified for each indicator. CONCLUSIONS: All five indicators performed well psychometrically. Until the meaning, relative importance, and usefulness of each scale is clarified in longitudinal work, decisions regarding which scale(s) are most informative will depend more on the content of the scales, the need for a multi- or unidimensional indicator, and whether or not the scale is theory based.

Development of symptoms of tobacco dependence in youths: 30 month follow up data from the DANDY study.

OBJECTIVE: To determine if there is a minimum duration, frequency or quantity of tobacco use required to develop symptoms of dependence. DESIGN AND SETTING: A retrospective/prospective longitudinal study of the natural history of tobacco dependence employing individual interviews conducted three times annually in two urban school systems over 30 months. Detailed histories of tobacco use were obtained including dates, duration, frequency, quantity, patterns of use, types of tobacco, and symptoms of dependence. PARTICIPANTS: A cohort of 679 seventh grade students (age 12-13 years). MAIN OUTCOME MEASURES: The report of any of 11 symptoms of dependence. RESULTS: Among 332 subjects who had used tobacco, 40% reported symptoms, with a median latency from the onset of monthly smoking of 21 days for girls and 183 days for boys. The median frequency of use at the onset of symptoms was two cigarettes, one day per week. The report of one or more symptoms predicted continued smoking through the end of follow up (odds ratio (OR) 44, 95% confidence interval (CI) 17 to 114, p < 0.001). CONCLUSIONS: Symptoms of tobacco dependence commonly develop rapidly after the onset of intermittent smoking, although individuals differ widely in this regard. Girls tend to develop symptoms faster. There does not appear to be a minimum nicotine dose or duration of use as a prerequisite for symptoms to appear. The development of a single symptom strongly predicted continued use, supporting the theory that the loss of autonomy over tobacco use begins with the first symptom of dependence.

Cigarette package design: opportunities for disease prevention.

OBJECTIVE: To learn how cigarette packages are designed and to determine to what extent cigarette packages are designed to target children. METHODS: A computer search was made of all Internet websites that post tobacco industry documents using the search terms: packaging, package design, package study, box design, logo, trademark and design study. All documents were retrieved electronically and analyzed by the first author for recurrent themes. DATA SYNTHESIS: Cigarette manufacturers devote a great deal of attention and expense to package design because it is central to their efforts to create brand images. Colors, graphic elements, proportioning, texture, materials and typography are tested and used in various combinations to create the desired product and user images. Designs help to create the perceived product attributes and project a personality image of the user with the intent of fulfilling the psychological needs of the targeted type of smoker. The communication of these images and attributes is conducted through conscious and subliminal processes. Extensive testing is conducted using a variety of qualitative and quantitative research techniques. CONCLUSION: The promotion of tobacco products through appealing imagery cannot be stopped without regulating the package design. The same marketing research techniques used by the tobacco companies can be used to design generic packaging and more effective warning labels targeted at specific consumers.

Sources of tobacco for youths in communities with strong enforcement of youth access laws.

AIM: To determine how youths obtain tobacco in communities with strong enforcement of tobacco sales laws. SETTING: Ten communities in Massachusetts with merchant compliance rates at or above 90%. METHODS: Paper surveys and focus group discussions with 68 adolescent smokers. RESULTS: Parents and friends are the primary sources of tobacco for new smokers. When stealing from parents can no longer satisfy the need for cigarettes, young adolescents ask strangers to buy them tobacco. For high school age smokers, teenage store clerks are a major source. Teenage clerks sell to other teenagers, steal tobacco, and help their friends steal from their employers. Friends who are 18 years of age or over are a second major source for older adolescents. Parents often purchase tobacco for older adolescents. CONCLUSION: Recommended actions include raising the minimum age for the purchase of tobacco to 21 years, and prohibiting individuals less than 21 years of age from selling tobacco.

Is the standard compliance check protocol a valid measure of the accessibility of tobacco to underage smokers?

OBJECTIVE: To determine if the standard compliance check protocol is a valid measure of the experience of underage smokers when purchasing tobacco in unfamiliar communities. SETTING: 160 tobacco outlets in eight Massachusetts communities where underage tobacco sales laws are vigorously enforced. PROCEDURE: Completed purchase rates were compared between underage smokers who behaved normally and inexperienced non-smoking youths who were not allowed to lie or present proof of age (ID). RESULTS: The "smoker protocol" increased the likelihood of a sale nearly sixfold over that for the non-smokers (odds ratio (OR) 5.7, 95% confidence interval (CI) 1.5 to 22). When the youths presented an ID with an underage birth date, the odds of a completed sale increased dramatically (OR 27, 95% CI 3.4 to 212). Clerks judged to be under 21 years of age were seven times more likely to make an illegal sale (OR 7.6, 95% CI 2.4 to 24.0). CONCLUSIONS: Commonly used compliance check protocols are too artificial to reflect accurately the experience of underage smokers. The validity of compliance checks might be improved by having youths present ID, and by employing either tobacco users, or non-tobacco users who are sufficiently experienced to mimic the self confidence exhibited by tobacco users in this situation. Consideration should be given to prohibiting the sale of tobacco by individuals under 21 years of age.

Measuring statewide merchant compliance with tobacco minimum age laws: the Massachusetts experience.

OBJECTIVES: This study evaluated merchant compliance with laws prohibiting the sale of tobacco to minors in Massachusetts. METHODS: Stratified cluster sampling was used to select outlets from which youths aged 13 to 17 years attempted to purchase tobacco. RESULTS: Illegal sales were more common when the youth purchasing the tobacco was older, when the clerk was male, and when tobacco was obtained from a self-service display or unlocked vending machine. Failure to request proof of age was the strongest predictor of illegal sales. CONCLUSIONS: Measured compliance rates are strongly influenced by the age of the youths used to purchase tobacco.

State and federal compliance with the Synar Amendment: federal fiscal year 1998.

BACKGROUND: The Synar Amendment requires states and territories to enact a law prohibiting the sale of tobacco to minors and to enforce that law in a manner that could reasonably be expected to decrease the availability of tobacco to minors. OBJECTIVE: To determine if the Department of Health and Human Services (DHHS) and applicant states and territories are complying with the Synar Amendment. DATA SOURCES: Block grant applications from 59 states and territories describing activities during the federal fiscal year 1998. MEASURES: Whether applicants had enacted a tobacco sales law without loopholes, conducted enforcement inspections, penalized violators, and conducted a valid statewide survey with violation rates below the permissible threshold, and whether DHHS actions were consistent with the statutory requirements of the Synar Amendment. RESULTS: Three applicants had laws containing loopholes, 6 failed to conduct enforcement inspections, 7 failed to prosecute violators, 2 failed to conduct a valid survey, and 10 failed to demonstrate compliance with violation rate goals. Fifteen applicants failed 1 or more criteria and 8 were ultimately penalized by DHHS. No measurable progress in reducing violation rates was reported by 30 states, with 16 reporting an increase during the previous year. Twenty-four applicants were granted delays. CONCLUSIONS: States that demonstrated remarkable progress were balanced by states with worsening performance; as a whole there was no significant national progress toward reducing the availability of tobacco to youths. This failure can be attributed to inadequate resources devoted to enforcement and reliance on merchant education in lieu of bona fide law enforcement.

What is the potential cost-effectiveness of enforcing a prohibition on the sale of tobacco to minors?

BACKGROUND: Enforcement programs to halt the sale of tobacco to youths have been implemented across the United States. The potential cost-effectiveness of enforcement was evaluated under a range of assumptions regarding cost and impact. METHODS: An enforcement model was constructed incorporating quarterly inspections of all tobacco vendors. The cost of discounted years of life saved was calculated using reported values regarding cost and a range of assumptions regarding the impact on youth tobacco use. RESULTS: Inspecting an estimated 543,000 tobacco outlets would cost up to $190 million annually. Costs range from $44 to $8,200 per year of life saved depending on the discount rate and assumptions regarding cost, and efficacy. To compete in cost-effectiveness with implementing smoking cessation guidelines, enforcement would have to produce a 5% reduction in adolescent smoking at a cost of no more than $250 per vendor. CONCLUSION: At this level of cost and effectiveness an enforcement program could save 10 times as many lives as the same amount spent on mammography or screening for colorectal carcinoma. A one-cent per pack cigarette tax could fully fund enforcement. Enforcement of tobacco sales laws deserves further study as one component of a multifaceted approach to tobacco use prevention.

Initial symptoms of nicotine dependence in adolescents.

OBJECTIVES: It has been assumed that nicotine dependence has a slow onset and occurs only after prolonged daily use of tobacco. A cohort of young adolescents was followed to determine when the first symptoms of nicotine dependence occur with respect to the duration and frequency of tobacco use. DESIGN: A cohort of 681 seventh grade students (age 12-13 years) from seven schools in two small cities in central Massachusetts was followed over one year. Detailed information regarding tobacco use was obtained in individual confidential interviews conducted in school three times over the year. The latency time to the onset of symptoms of nicotine dependence was measured from the time a subject first smoked at a frequency of at least once per month. RESULTS: 22% of the 95 subjects who had initiated occasional smoking reported a symptom of nicotine dependence within four weeks of initiating monthly smoking. One or more symptoms were reported by 60 (63%) of these 95 subjects. Of the 60 symptomatic subjects, 62% had reported experiencing their first symptom before smoking daily or began smoking daily only upon experiencing their first symptom. DISCUSSION: The first symptoms of nicotine dependence can appear within days to weeks of the onset of occasional use, often before the onset of daily smoking. The existence of three groups of individuals-rapid onset, slower onset, and resistant-distinguishable from one another by their susceptibility to nicotine dependence, is postulated.

State and federal compliance with the Synar amendment: federal fiscal year 1997.

BACKGROUND: The Synar Amendment requires states and territories to enact a law prohibiting the sale of tobacco to minors and to enforce that law in a manner that could reasonably be expected to decrease the availability of tobacco to minors. OBJECTIVE: To determine whether the Department of Health and Human Services (DHHS) and applicant states and territories are complying with the Synar Amendment. DATA SOURCES: Block grant applications from 59 states and territories describing activities during federal fiscal year 1997. MEASURES: Whether applicants had enacted a tobacco sales law without loopholes, conducted enforcement inspections, penalized violators, and conducted a valid statewide survey with violation rates below the permissible threshold, and whether DHHS actions were consistent with the statutory requirements of the Synar Amendment. RESULTS: Three applicants had laws containing loopholes, 8 failed to conduct enforcement inspections, 8 failed to prosecute violators, 6 failed to conduct a valid survey, and 8 failed to demonstrate compliance with violation rate targets. Fifteen applicants failed 1 or more criteria, but none was ultimately penalized by DHHS. Fourteen sources of bias were identified in state survey protocols that could substantially lower reported violation rates. CONCLUSIONS: A few states did a remarkable job with enforcement, while many others made little effort. Because the DHHS regulations are so weak and DHHS is willing to accept biased surveys, states can be in full compliance with the regulations without ever enforcing their laws or having any impact on the availability of tobacco to minors.

A comparison of the advertising and accessibility of cigars, cigarettes, chewing tobacco, and loose tobacco.

BACKGROUND: Tobacco products were compared in regard to their price, point-of-purchase advertising, accessibility to shoplifters, and rate of sale to minors. METHODS: An experimental design compared the rates of illegal sales to minors of cigarettes, chewing tobacco, and cigars. Observational surveys of 102 stores measured the number of advertisements for four tobacco products, the manner in which products were displayed, and their accessibility to shoplifters. RESULTS: Illegal sales rates were similar for cigarettes, chewing tobacco, and cigars. Cigars were the least expensive. Cigarettes were the most heavily advertised product, followed by chewing tobacco, cigars, and loose tobacco. Cigarettes were the most accessible to shoplifters. All types of tobacco products were displayed to permit the package to serve as advertising. CONCLUSIONS: Point-of-purchase advertising for cigars may be increasing, and their lower price makes them more affordable to youths. Food and Drug Administration regulations that limit point-of-purchase advertising for tobacco products should be expanded to include cigars. Manufacturers pay retailers for the placement of product displays that allow the package to be used as an advertisement without the appearance of the Surgeon General's warning. Generic packaging may be necessary to protect children from point-of-purchase advertising.

Are the federal and state governments complying with the Synar Amendment?

BACKGROUND: In 1992, Congress enacted the Synar Amendment, requiring states and territories to enact a law prohibiting the sale of tobacco to minors and to enforce that law in a manner that could reasonably be expected to decrease the availability of tobacco to minors. The Department of Health and Human Services (DHHS) was mandated to withhold block grant funding from noncompliant states. OBJECTIVE: To determine if DHHS and applicant states and territories are complying with the Synar Amendment. DATA SOURCES: Fiscal year 1997 substance abuse block grant applications from 59 states and territories. MAIN OUTCOME MEASURES: Whether applicants had enacted a tobacco sales law, conducted enforcement inspections, penalized violators, and conducted a statewide survey, and whether DHHS regulations and actions were consistent with the statutory requirements of the Synar Amendment. RESULTS: Two applicants failed to enact appropriate laws, 15 failed to conduct enforcement inspections, 18 failed to provide a single example of a violator being penalized, and 1 failed to conduct a survey. Nineteen applicants failed to meet the statutory requirements, but none were sanctioned by DHHS as required by the Synar Amendment. The DHHS regulations, as implemented, do not require states to enforce their laws or to achieve illegal tobacco sales rates low enough to reduce the availability of tobacco to minors. CONCLUSIONS: The states and DHHS are violating the statutory requirements of the Synar Amendment, rendering it ineffective. Few states have implemented effective enforcement programs, and national surveys confirm that there has been no measurable reduction in the availability of tobacco to youths.