CYP2A6 metabolism in the development of smoking behaviors in young adults.

Cytochrome P450 2A6 (CYP2A6) encodes the enzyme responsible for the majority of nicotine metabolism. Previous studies support that slow metabolizers smoke fewer cigarettes once nicotine dependent but provide conflicting results on the role of CYP2A6 in the development of dependence. By focusing on the critical period of young adulthood, this study examines the relationship of CYP2A6 variation and smoking milestones. A total of 1209 European American young adults enrolled in the Collaborative Study on the Genetics of Alcoholism were genotyped for CYP2A6 variants to calculate a previously well-validated metric that estimates nicotine metabolism. This metric was not associated with the transition from never smoking to smoking initiation nor with the transition from initiation to daily smoking (P > 0.4). But among young adults who had become daily smokers (n = 506), decreased metabolism was associated with increased risk of nicotine dependence (P = 0.03) (defined as Fagerström Test for Nicotine Dependence score ≥4). This finding was replicated in the Collaborative Genetic Study of Nicotine Dependence with 335 young adult daily smokers (P = 0.02). Secondary meta-analysis indicated that slow metabolizers had a 53 percent increased odds (OR = 1.53, 95 percent CI 1.11-2.11, P = 0.009) of developing nicotine dependence compared with normal metabolizers. Furthermore, secondary analyses examining four-level response of time to first cigarette after waking (>60, 31-60, 6-30, ≤5 minutes) demonstrated a robust effect of the metabolism metric in Collaborative Study on the Genetics of Alcoholism (P = 0.03) and Collaborative Genetic Study of Nicotine Dependence (P = 0.004), illustrating the important role of this measure of dependence. These findings highlight the complex role of CYP2A6 variation across different developmental stages of smoking behaviors.

Variants in two adjacent genes, EGLN2 and CYP2A6, influence smoking behavior related to disease risk via different mechanisms.

Genome-wide significant associations with cigarettes per day (CPD) and risk for lung cancer and chronic obstructive pulmonary disease (COPD) were previously reported in a region of 19q13, including CYP2A6 (nicotine metabolism enzyme) and EGLN2 (hypoxia response). The associated single nucleotide polymorphisms (SNPs) were assumed to be proxies for functional variation in CYP2A6. Here, we demonstrate that when CYP2A6 and EGLN2 genotypes are analyzed together, the key EGLN2 variant, rs3733829, is not associated with nicotine metabolism independent of CYP2A6, but is nevertheless independently associated with CPD, and with breath carbon monoxide (CO), a phenotype associated with cigarette consumption and relevant to hypoxia. SNPs in EGLN2 are also associated with nicotine dependence and with smoking efficiency (CO/CPD). These results indicate a previously unappreciated novel mechanism behind genome-wide significant associations with cigarette consumption and disease risk unrelated to nicotine metabolism.

Birth weight and asthma incidence by asthma phenotype pattern in a racially diverse cohort followed through adolescence.

OBJECTIVE: Low birth weight (LBW) has been shown to be an independent risk factor for asthma. We hypothesized that LBW would have its greatest impact on early onset disease. METHODS: A racially diverse cohort of children born from 1983 to 1985 at two hospitals, one urban and one suburban in the same metropolitan area, and oversampled for babies weighing ≤2500 g, was identified retrospectively when the children were 6 years of age and followed periodically. At the age 17 years study visit, cohort members and their parent/guardians were separately interviewed face-to-face regarding the subject's history of asthma using the standardized ISAAC questionnaire. We measured the cumulative incidence of asthma from birth through adolescence defined by age of diagnosis and persistence/remittance. RESULTS: Six-hundred and eighty teens (82.6% of the original cohort) were included in the analyses, 387 with LBW and 293 of normal birth weight. The prevalence of physician-diagnosed "Current Asthma" was associated with LBW (p = 0.003 for trend), with patterns stronger in males and whites. LBW was associated most strongly with Late Onset Persistent asthma (current asthma that was diagnosed after 8 years); p for trend 0.032. This trend was again most evident in males and whites. None of the asthma categories classified as "remittent" were statistically associated with LBW. CONCLUSIONS: LBW was not associated with diagnosed asthma that remitted before age 17 years. LBW was associated with asthma diagnosis in mid-childhood that persisted through adolescence, suggesting that the asthmagenic effects of LBW can become evident post the early years of childhood and persist into adulthood.

Distinct loci in the CHRNA5/CHRNA3/CHRNB4 gene cluster are associated with onset of regular smoking.

Neuronal nicotinic acetylcholine receptor (nAChR) genes (CHRNA5/CHRNA3/CHRNB4) have been reproducibly associated with nicotine dependence, smoking behaviors, and lung cancer risk. Of the few reports that have focused on early smoking behaviors, association results have been mixed. This meta-analysis examines early smoking phenotypes and SNPs in the gene cluster to determine: (1) whether the most robust association signal in this region (rs16969968) for other smoking behaviors is also associated with early behaviors, and/or (2) if additional statistically independent signals are important in early smoking. We focused on two phenotypes: age of tobacco initiation (AOI) and age of first regular tobacco use (AOS). This study included 56,034 subjects (41 groups) spanning nine countries and evaluated five SNPs including rs1948, rs16969968, rs578776, rs588765, and rs684513. Each dataset was analyzed using a centrally generated script. Meta-analyses were conducted from summary statistics. AOS yielded significant associations with SNPs rs578776 (beta = 0.02, P = 0.004), rs1948 (beta = 0.023, P = 0.018), and rs684513 (beta = 0.032, P = 0.017), indicating protective effects. There were no significant associations for the AOI phenotype. Importantly, rs16969968, the most replicated signal in this region for nicotine dependence, cigarettes per day, and cotinine levels, was not associated with AOI (P = 0.59) or AOS (P = 0.92). These results provide important insight into the complexity of smoking behavior phenotypes, and suggest that association signals in the CHRNA5/A3/B4 gene cluster affecting early smoking behaviors may be different from those affecting the mature nicotine dependence phenotype.

Rare missense variants in CHRNB4 are associated with reduced risk of nicotine dependence.

Genome-wide association studies have identified common variation in the CHRNA5-CHRNA3-CHRNB4 and CHRNA6-CHRNB3 gene clusters that contribute to nicotine dependence. However, the role of rare variation in risk for nicotine dependence in these nicotinic receptor genes has not been studied. We undertook pooled sequencing of the coding regions and flanking sequence of the CHRNA5, CHRNA3, CHRNB4, CHRNA6 and CHRNB3 genes in African American and European American nicotine-dependent smokers and smokers without symptoms of dependence. Carrier status of individuals harboring rare missense variants at conserved sites in each of these genes was then compared in cases and controls to test for an association with nicotine dependence. Missense variants at conserved residues in CHRNB4 are associated with lower risk for nicotine dependence in African Americans and European Americans (AA P = 0.0025, odds-ratio (OR) = 0.31, 95% confidence-interval (CI) = 0.31-0.72; EA P = 0.023, OR = 0.69, 95% CI = 0.50-0.95). Furthermore, these individuals were found to smoke fewer cigarettes per day than non-carriers (AA P = 6.6 × 10(-5), EA P = 0.021). Given the possibility of stochastic differences in rare allele frequencies between groups replication of this association is necessary to confirm these findings. The functional effects of the two CHRNB4 variants contributing most to this association (T375I and T91I) and a missense variant in CHRNA3 (R37H) in strong linkage disequilibrium with T91I were examined in vitro. The minor allele of each polymorphism increased cellular response to nicotine (T375I P = 0.01, T91I P = 0.02, R37H P = 0.003), but the largest effect on in vitro receptor activity was seen in the presence of both CHRNB4 T91I and CHRNA3 R37H (P = 2 × 10(-6)).

A non-parametric approach for detecting gene-gene interactions associated with age-at-onset outcomes.

BACKGROUND: Cox-regression-based methods have been commonly used for the analyses of survival outcomes, such as age-at-disease-onset. These methods generally assume the hazard functions are proportional among various risk groups. However, such an assumption may not be valid in genetic association studies, especially when complex interactions are involved. In addition, genetic association studies commonly adopt case-control designs. Direct use of Cox regression to case-control data may yield biased estimators and incorrect statistical inference. RESULTS: We propose a non-parametric approach, the weighted Nelson-Aalen (WNA) approach, for detecting genetic variants that are associated with age-dependent outcomes. The proposed approach can be directly applied to prospective cohort studies, and can be easily extended for population-based case-control studies. Moreover, it does not rely on any assumptions of the disease inheritance models, and is able to capture high-order gene-gene interactions. Through simulations, we show the proposed approach outperforms Cox-regression-based methods in various scenarios. We also conduct an empirical study of progression of nicotine dependence by applying the WNA approach to three independent datasets from the Study of Addiction: Genetics and Environment. In the initial dataset, two SNPs, rs6570989 and rs2930357, located in genes GRIK2 and CSMD1, are found to be significantly associated with the progression of nicotine dependence (ND). The joint association is further replicated in two independent datasets. Further analysis suggests that these two genes may interact and be associated with the progression of ND. CONCLUSIONS: As demonstrated by the simulation studies and real data analysis, the proposed approach provides an efficient tool for detecting genetic interactions associated with age-at-onset outcomes.

Assessing interchangeability at cluster levels with multiple-informant data.

Studies examining the relationship between neighborhood social disorder and health often rely on multiple informants. Such studies assume interchangeability of the latent constructs derived from multiple-informant data. Existing methods examining this assumption do not clearly delineate the uncertainty at individual levels from that at neighborhood levels. We propose a multilevel variance component factor model that allows this delineation. Data come from a survey of a representative sample of children born between 1983 and 1985 in the inner city of Detroit and nearby middle-class suburbs. Results indicate that the informant-level models tend to exaggerate the effect of places because of differences between persons. Our evaluations of different methodologies lead to the recommendation of the multilevel variance component factor model whenever multiple-informant reports can be aggregated at a neighborhood level.

Protocol for a collaborative meta-analysis of 5-HTTLPR, stress, and depression.

BACKGROUND: Debate is ongoing about what role, if any, variation in the serotonin transporter linked polymorphic region (5-HTTLPR) plays in depression. Some studies report an interaction between 5-HTTLPR variation and stressful life events affecting the risk for depression, others report a main effect of 5-HTTLPR variation on depression, while others find no evidence for either a main or interaction effect. Meta-analyses of multiple studies have also reached differing conclusions. METHODS/DESIGN: To improve understanding of the combined roles of 5-HTTLPR variation and stress in the development of depression, we are conducting a meta-analysis of multiple independent datasets. This coordinated approach utilizes new analyses performed with centrally-developed, standardized scripts. This publication documents the protocol for this collaborative, consortium-based meta-analysis of 5-HTTLPR variation, stress, and depression. STUDY ELIGIBILITY CRITERIA: Our goal is to invite all datasets, published or unpublished, with 5-HTTLPR genotype and assessments of stress and depression for at least 300 subjects. This inclusive approach is to minimize potential impact from publication bias. DATA SOURCES: This project currently includes investigators from 35 independent groups, providing data on at least N = 33,761 participants.The analytic plan was determined prior to starting data analysis. Analyses of individual study datasets will be performed by the investigators who collected the data using centrally-developed standardized analysis scripts to ensure a consistent analytical approach across sites. The consortium as a group will review and interpret the meta-analysis results. DISCUSSION: Variation in 5-HTTLPR is hypothesized to moderate the response to stress on depression. To test specific hypotheses about the role of 5-HTTLPR variation on depression, we will perform coordinated meta-analyses of de novo results obtained from all available data, using variables and analyses determined a priori. Primary analyses, based on the original 2003 report by Caspi and colleagues of a GxE interaction will be supplemented by secondary analyses to help interpret and clarify issues ranging from the mechanism of effect to heterogeneity among the contributing studies. Publication of this protocol serves to protect this project from biased reporting and to improve the ability of readers to interpret the results of this specific meta-analysis upon its completion.

A genome-wide association study of alcohol dependence.

Excessive alcohol consumption is one of the leading causes of preventable death in the United States. Approximately 14% of those who use alcohol meet criteria during their lifetime for alcohol dependence, which is characterized by tolerance, withdrawal, inability to stop drinking, and continued drinking despite serious psychological or physiological problems. We explored genetic influences on alcohol dependence among 1,897 European-American and African-American subjects with alcohol dependence compared with 1,932 unrelated, alcohol-exposed, nondependent controls. Constitutional DNA of each subject was genotyped using the Illumina 1M beadchip. Fifteen SNPs yielded P < 10(-5), but in two independent replication series, no SNP passed a replication threshold of P < 0.05. Candidate gene GABRA2, which encodes the GABA receptor alpha2 subunit, was evaluated independently. Five SNPs at GABRA2 yielded nominal (uncorrected) P < 0.05, with odds ratios between 1.11 and 1.16. Further dissection of the alcoholism phenotype, to disentangle the influence of comorbid substance-use disorders, will be a next step in identifying genetic variants associated with alcohol dependence.

Multiple independent loci at chromosome 15q25.1 affect smoking quantity: a meta-analysis and comparison with lung cancer and COPD.

Recently, genetic association findings for nicotine dependence, smoking behavior, and smoking-related diseases converged to implicate the chromosome 15q25.1 region, which includes the CHRNA5-CHRNA3-CHRNB4 cholinergic nicotinic receptor subunit genes. In particular, association with the nonsynonymous CHRNA5 SNP rs16969968 and correlates has been replicated in several independent studies. Extensive genotyping of this region has suggested additional statistically distinct signals for nicotine dependence, tagged by rs578776 and rs588765. One goal of the Consortium for the Genetic Analysis of Smoking Phenotypes (CGASP) is to elucidate the associations among these markers and dichotomous smoking quantity (heavy versus light smoking), lung cancer, and chronic obstructive pulmonary disease (COPD). We performed a meta-analysis across 34 datasets of European-ancestry subjects, including 38,617 smokers who were assessed for cigarettes-per-day, 7,700 lung cancer cases and 5,914 lung-cancer-free controls (all smokers), and 2,614 COPD cases and 3,568 COPD-free controls (all smokers). We demonstrate statistically independent associations of rs16969968 and rs588765 with smoking (mutually adjusted p-values<10(-35) and <10(-8) respectively). Because the risk alleles at these loci are negatively correlated, their association with smoking is stronger in the joint model than when each SNP is analyzed alone. Rs578776 also demonstrates association with smoking after adjustment for rs16969968 (p<10(-6)). In models adjusting for cigarettes-per-day, we confirm the association between rs16969968 and lung cancer (p<10(-20)) and observe a nominally significant association with COPD (p = 0.01); the other loci are not significantly associated with either lung cancer or COPD after adjusting for rs16969968. This study provides strong evidence that multiple statistically distinct loci in this region affect smoking behavior. This study is also the first report of association between rs588765 (and correlates) and smoking that achieves genome-wide significance; these SNPs have previously been associated with mRNA levels of CHRNA5 in brain and lung tissue.

Migraine headaches and suicide attempt.

BACKGROUND: Previous cross-sectional studies reported an increased risk of suicide attempt in persons with migraine headache, which was sustained when psychiatric comorbidity was statistically controlled. OBJECTIVE: To estimate the risk of suicide attempt in persons with migraine vs controls with no history of severe headache, using prospective data and validated diagnostic assessment. To examine the specificity of the migraine-suicide attempt risk by comparing it to the risk associated with non-migraine headache of comparable severity and disability. METHODS: A cohort of persons with migraine (n = 496), non-migraine severe headaches (n = 151), and controls with no history of severe headache (n = 539) was randomly selected from the general community, assessed in 1997 and reassessed 2 years later. RESULTS: Persons with migraine had an increased risk of suicide attempt during the 2-year follow-up period, compared with controls. Odds ratio, adjusted for sex, psychiatric disorder, and previous history of suicide attempt at baseline was 4.43 (95% confidence interval [CI] 1.93, 10.2). Persons with non-migraine headache of comparable intensity and disability also had an increased risk of suicide attempt, compared to controls: odds ratio, adjusted for the same covariates, was 6.20 (95% CI 2.40, 16.0). The difference between the 2 estimates was not significant. In the entire sample, headache severity at baseline predicted suicide attempt: a difference of 1 standard deviation (SD) in pain score increased the risk of suicide attempt by 79%, adjusting for sex and psychiatric disorders. CONCLUSIONS: The results suggest the possibility that pain severity might account in part for the increased risk of suicide attempt associated with migraine.

Dissection of the phenotypic and genotypic associations with nicotinic dependence.

INTRODUCTION: Strong evidence demonstrates that nicotine dependence is associated with 4 genetic variants rs16969968, rs6474412, rs3733829, and rs1329650 in large-scale Genome-Wide Association Studies. We examined how these identified genetic variants relate to nicotine dependence defined by different categorical and dimensional measures. METHODS: Four genetic variants were analyzed in 2,047 subjects of European descent (1,062 cases and 985 controls). Nicotine dependence was assessed with multiple smoking measures, including the Fagerström Test for Nicotine Dependence, the Diagnostic and Statistical Manual for Mental Disorders-IV (DSM-IV) nicotine dependence, the Nicotine Dependence Syndrome Scale, and the Wisconsin Inventory of Smoking Dependence Motives. Single-item measures of cigarettes per day (CPD) and time to first cigarette (TTF) in the morning were also examined. RESULTS: Among the variants, association effect sizes were largest for rs16969968, with measures of craving and heavy smoking, especially cigarettes smoked per day, showing the largest effects. Significant but weaker associations were found for rs6474412 and rs3733729 but not for rs1329650. None of the more comprehensive measures of smoking behaviors yielded stronger genetic associations with these variants than did CPD. CONCLUSIONS: CPD is an important simple measure that captures in part the genetic associations of CHRNA5 and nicotine dependence, even when other more comprehensive measures of smoking behaviors are examined. The CHRNA5 gene is associated with heavy compulsive smoking and craving; this should inform the mission to improve the diagnostic validity of DSM-V.

Inclusion of African Americans in genetic studies: what is the barrier?

To facilitate an increase in the amount of data on minority subjects collected for genetic databases, the authors attempted to clarify barriers to African-American participation in genetic studies. They randomly sampled 78,072 subjects from the community (Missouri Family Registry, 2002-2007). Of these, 28,658 participated in a telephone screening interview, 3,179 were eligible to participate in the genetic study, and 1,919 participated in the genetic study. Response rates were examined in relation to the proportion of subjects in the area who were African-American according to US Census 2000 zip code demographic data. Compared with zip codes with fewer than 5% African Americans (average = 2% African-American), zip codes with at least 60% African Americans (average = 87% African-American) had higher proportions of subjects with an incorrect address or telephone number but lower proportions of subjects who did not answer the telephone and subjects who refused the telephone interview (P < 0.0001). Based on reported race from the telephone screening, 71% of eligible African Americans and 57% of eligible European Americans participated in the genetic study (P < 0.0001). The results of this study suggest that increasing the number of African Americans in genetic databases may be achieved by increasing efforts to locate and contact them.

Cigarette smoking reduction and changes in nicotine dependence.

INTRODUCTION: The relationship of nicotine dependence (ND) to smoking behavior and cessation has been well characterized. However, little is known about the association between smoking reduction (SR) and ND. METHODS: We retrospectively evaluated the lifetime prevalence and extent of SR and whether ND as assessed by a modified Fagerström Test for Nicotine Dependence (FTND) score without cigarettes per day (CPD) and time-to-first cigarette changed with reductions in CPD. As part of the Collaborative Study of the Genetics of Nicotine Dependence (COGEND), 47,777 individuals from 2 mid-Western metropolitan areas were identified for a community-based telephone screening, yielding 6,955 current daily smokers ages 25-44 years (European-American, n = 5,135 and Black, n = 1,820). The FTND was administered to measure current ND and peak ND in respondents whose current daily CPD is lower than their reported lifetime peak. RESULTS: About 44% (n = 3,077) of the sample reported reducing their smoking from their lifetime peak, with a mean reduction of 14.4 CPD (SD = 8.9) or a 54.0% reduction compared with peak smoking. Controlling for peak smoking and years smoked, the magnitude of SR was associated with declines in ND excluding the direct contribution of CPD. CONCLUSIONS: Self-reported SR was associated with reduced levels of ND. The impact of this reduction on smoking cessation and health risks and smoking cessation requires further study, particularly given the retrospective nature of the present dataset.

Behavior problems at ages 6 and 11 and high school academic achievement: longitudinal latent variable modeling.

Previous studies documented long-run effects of behavior problems at the start of school on academic achievement. However, these studies did not examine whether the observed effects of early behavior problems are explained by more proximate behavior problems, given the tendency of children's behavior problems to persist. Latent variable modeling was applied to estimate the effects of behavior problems at ages 6 and 11 on academic achievement at age 17, using data from a longitudinal study (n=823). Behavior problems at ages 6 and 11, each stage independently of the other, predicted lower math and reading test scores at age 17, controlling for intelligence quotient (IQ), birth weight, maternal characteristics, family and community environment, and taking into account behavior problems at age 17. Behavior problems at the start of school, independent of later behavior problems, exert lingering effects on achievement by impeding the acquisition of cognitive skills that are the foundation for later academic progress.

The 10-year risk of verified motor vehicle crashes in relation to physiologic sleepiness.

STUDY OBJECTIVES: The purpose of this study was to determine the risk of DMV documented crashes as a function of physiological sleepiness in a population-based sample. DESIGN: 24-hour laboratory assessment (nocturnal polysomnogram and daytime MSLT) and 10-year crash rate based on DMV obtained accident records. PARTICIPANTS: 618 individuals (mean age = 41.6 +/- 12.8; 48.5% male) were recruited from the general population of southeastern Michigan using random-digit dialing techniques. RESULTS: Subjects were divided into 3 groups based on their average MSLT latency (in minutes) as follows: excessively sleepy, 0.0 to < or = 5.0 (n = 69); moderately sleepy, 5.0 to < or = 10.0 (n = 204); and alert, > 10 (n = 345). Main outcome measures were DMV data on accidents from 1995-2005. Rates for all accidents in the 3 MSLT groups were: excessively sleepy = 59.4%, moderately sleepy = 52.5%, alert = 47.3%. Excessively sleepy subjects were at significantly greater risk of an accident over the 10-year period compared to alert subjects. A similar relation was observed when we limited the database to those accident victims with severe injury (excessively sleepy = 4.3%, moderately sleepy = 0.5%, alert = 0.6%; P = 0.028). When the victim was the only occupant of the car, subjects in the lowest MSLT group (highest sleepiness) had the greatest crash rate compared with alert individuals (excessively sleepy = 52.2%, moderately sleepy = 42.2%, alert = 37.4%; P = 0.022). INTERVENTIONS: N/A. CONCLUSIONS: These data demonstrate that the MSLT, a physiological measure of sleepiness, is predictive of an increased risk of DMV documented automotive crashes in the general population.

Incorporating age at onset of smoking into genetic models for nicotine dependence: evidence for interaction with multiple genes.

Nicotine dependence is moderately heritable, but identified genetic associations explain only modest portions of this heritability. We analyzed 3369 SNPs from 349 candidate genes and investigated whether incorporation of SNP-by-environment interaction into association analyses might bolster gene discovery efforts and prediction of nicotine dependence. Specifically, we incorporated the interaction between allele count and age at onset of regular smoking (AOS) into association analyses of nicotine dependence. Subjects were from the Collaborative Genetic Study of Nicotine Dependence and included 797 cases ascertained for Fagerström nicotine dependence and 811 non-nicotine-dependent smokers as controls, all of European descent. Compared with main effect models, SNP x AOS interaction models resulted in higher numbers of nominally significant tests, increased predictive utility at individual SNPs and higher predictive utility in a multi-locus model. Some SNPs previously documented in main effect analyses exhibited improved fits in the joint analysis, including rs16969968 from CHRNA5 and rs2314379 from MAP3K4. CHRNA5 exhibited larger effects in later-onset smokers, in contrast with a previous report that suggested the opposite interaction (Weiss et al. 2008). However, a number of SNPs that did not emerge in main effect analyses were among the strongest findings in the interaction analyses. These include SNPs located in GRIN2B (P = 1.5 x 10(-5)), which encodes a subunit of the N-methyl-D-aspartate receptor channel, a key molecule in mediating age-dependent synaptic plasticity. Incorporation of logically chosen interaction parameters, such as AOS, into genetic models of substance use disorders may increase the degree of explained phenotypic variation and constitutes a promising avenue for gene discovery.

The 9/11 terrorist attack and posttraumatic stress disorder revisited.

Research published in the aftermath of the 9/11 terrorist attack reported elevated rates of posttraumatic stress disorder (PTSD) in the US population (4.3%-17.0%), attributable to indirect exposure through the media. We use data from a national survey conducted in 2004 to 2005 (National Epidemiologic Survey on Alcohol and Related Conditions Wave 2) (n = 34,653). The list of traumatic events covered in the survey included indirect exposure to 9/11 through media coverage. Respondents who endorsed more than 1 traumatic event were asked to single out "the worst event" they had ever experienced. The worst event (or the only event) was the index event for diagnosing PTSD. Indirect experience of 9/11 had the lowest PTSD risk of all the traumatic events in the list, 1.3%. In the subset that endorsed only 9/11 indirect exposure (n = 3981), the PTSD risk was 0.3%. Of the total sample, 0.7% experienced PTSD in relation to indirect 9/11. Explanations for the lower estimates are discussed.

Parental monitoring at age 11 and smoking initiation up to age 17 among Blacks and Whites: a prospective investigation.

INTRODUCTION: Parental monitoring has been identified as a predictor of adolescent smoking initiation. However, it is uncertain if the association is uniform across different racial groups. METHODS: Random samples of low birth-weight and normal birth-weight children were drawn from newborn discharge lists (1983-1985) of two major hospitals in southeast Michigan, one serving an inner city and the other serving suburbs. Assessments occurred at ages 6, 11, and 17 years. Statistical analysis was conducted on children with data on parent monitoring at age 11 and tobacco use at age 17 who had never smoked a cigarette up to age 11 (n = 572). Multiple logistic regression was used to examine the association between parent monitoring and children's smoking initiation. Two-way interactions were tested. RESULTS: The relationship between parent monitoring at age 11 and child smoking initiation from ages 11 to 17 varied by race. Among White children, an increase of 1 point on the parent monitoring scale signaled an 11% reduction in the odds of initiating smoking by age 17. In contrast, parent monitoring was not significantly associated with smoking initiation among Black children. DISCUSSION: The results suggest a differential influence of parent monitoring on adolescent smoking between White and Black children. Future research would benefit from close attention to parental goals and concerns and to extra-familial factors that shape smoking behavior across racially and socially disparate communities.

Early childhood behavior trajectories and the likelihood of experiencing a traumatic event and PTSD by young adulthood.

This study modeled children's trajectories of teacher rated aggressive-disruptive behavior problems assessed at six time points between the ages of 6 and 11 and explored the likelihood of being exposed to DSM-IV qualifying traumatic events and posttraumatic stress disorder (PTSD) in 837 urban first graders (71% African American) followed-up for 15 years. Childhood trajectories of chronic high or increasing aggressive-disruptive behavior distinguished males more likely to be exposed to an assaultive violence event as compared to males with a constant course of low behavior problems (OR(chronic high) = 2.8, 95% CI = 1.3, 6.1 and OR(increasing) = 4.5, 95% CI = 2.3, 9.1, respectively). Among females, exposure to traumatic events and vulnerability to PTSD did not vary by behavioral trajectory. The findings illustrate that repeated assessments of disruptive classroom behavior during early school years identifies more fully males at increased risk for PTSD-level traumatic events, than a single measure at school entry does.