David S. Timberlake

Monoamine oxidase A (MAOA) and antisocial behaviors in the presence of childhood and adolescent maltreatment

There is a robust relationship between the experience of maltreatment in childhood and later antisocial behaviors amongst adolescents and adults. Animal and human studies suggest that variation in monoamine oxidase A (MAOA) genotype may moderate the effects of maltreatment. Self‐reported conduct problems and criminal convictions amongst sibling‐pairs from the National Longitudinal Study of Adolescent Health were tested for association with reports of maltreatment before and after the age of 12. MAOA promoter polymorphisms were tested for possible moderation effects. Maltreatment predicted conduct problems and criminal convictions. MAOA genotype did not have a significant moderating effect in any of the six analyses that were conducted. We did not replicate a previous report that MAOA polymorphisms moderated the relationship between maltreatment and conduct problems. There was, however, a non‐significant trend in the predicted direction. Additional studies will be needed before firm conclusions can be drawn about this hypothesized genotype–environment interaction.

Case-control and within-family tests for an association between conduct disorder and 5HTTLPR†

Several lines of research have suggested that serotonin dysfunction is associated with aggression, impulsivity, and antisocial behavior. A functional polymorphism in the promoter region (s, short and l, long allele variant) of the serotonin transporter gene (SLC6A4) that results in decreased transcription of the serotonin transporter gene has been linked with such serotonin dysfunction. To test for an association between 5HTTLPR genotype and conduct disorder diagnosis/aggression. Analysis for association between 5HTTLPR and conduct disorder/aggression using a case‐control design and the transmission disequilibrium test. Conduct‐disordered adolescents, who were drawn from admissions to a program that treats adolescents with serious substance and behavior problems, and conduct‐disordered siblings of these patients (n, 297) were compared with non‐conduct‐disordered control adolescents and non‐conduct‐disordered siblings of these controls (n, 93). Second, using patient families where parental DNA was available, transmission disequilibrium tests were conducted for two phenotypes: (1) conduct disorder (74 trios), and (2) conduct disorder with at least one aggressive symptom (57 trios). Case‐control analyses suggested a strong association between the ss genotype and conduct disorder (χ  22  = 14.3; P < 0.01). Within‐family analyses for conduct disorder with at least one aggressive symptom significantly favored greater transmission of the s‐allele to affected offspring (χ  tdt2  = 4.13; P = 0.04); for conduct disorder, without aggressive symptoms, however, results were non‐significant (χ  tdt2  = 1.61; P = 0.20). These data suggest that the s‐allele may confer some risk for aggressive behavior or may be in linkage disequilibrium with such an allele.

The Moderating Effects of Religiosity on the Genetic and Environmental Determinants of Smoking Initiation

Although a number of studies have shown that various measures of religiosity are inversely correlated with smoking behavior, none of these studies have used genetically informative samples to test for a gene-environment interaction between the determinants of smoking initiation and religiosity. We tested the moderating effects of three measures of religiosity (religious affiliation, organizational religious activity, and self-rated religiousness) on the genetic and environmental determinants of smoking initiation in 237 monozygotic twin pairs, 315 dizygotic twin pairs, 779 full-sibling pairs, and 233 half-sibling pairs in young adults surveyed from the third wave of the National Longitudinal Study of Adolescent Health. Primary analyses incorporated all sibling pairs, irrespective of whether they were concordant or discordant for the environmental moderator, in models designed to account for the confounding effects of a gene-environment correlation. High levels of self-rated religiousness attenuated the additive genetic component for smoking initiation and were associated with a lower prevalence of smoking initiation. Although all three measures of religiosity were associated with lower rates of smoking initiation, only self-rated religiousness moderated genetic influences on the liability for smoking.

An association between the DAT1 polymorphism and smoking behavior in young adults from the national longitudinal study of adolescent health.

Associations between smoking behavior and polymorphisms in the dopaminergic genes (DAT1 and DRD2) were tested by using within- and between-family measures of allelic transmission in 2,448 young adults from the National Longitudinal Study of Adolescent Health. The 9-repeat allele of the dopamine transporter gene polymorphism (DAT1) was inversely associated with smoking in samples that included all subjects and only those who had initiated smoking, accounting for approximately 1% of the variance. Never smokers and current nonsmokers had an excess transmission of the 9-repeat allele compared with regular smokers, suggesting a protective effect of the 9-repeat allele, which is hypothesized to alter synaptic dopamine levels.

A comparison of drug use and dependence between blunt smokers and other cannabis users.

Ethnographic studies have suggested that blunt smokers represent a subculture of cannabis users whose drug use is moderated by social norms. The objective of this study was to compare rates of cannabis dependence/abuse and nicotine dependence between blunt and other cannabis smokers. The sample included adolescents and young adults (n = 4348) who reported some form of past-month cannabis use in the 2004 National Survey on Drug Use and Health. Compared to smokers who never used blunts, blunt smokers had significantly greater odds of being dependent on cannabis and tobacco. Associations with cannabis dependence/abuse remained statistically significant with adjustment for smoking frequency and demographic characteristics. These findings highlight the need for differentiating types of cannabis users in epidemiologic studies. The studys limitations are noted.

Use of propensity score matching in evaluating smokeless tobacco as a gateway to smoking

INTRODUCTION The contentious debate over the promotion of Swedish snus, a form of moist snuff, as an alternative to cigarettes has often focused on the products potential as a gateway to smoking. Findings from prospective studies in the United States have suggested that smokeless tobacco (SLT) is a significant predictor of smoking onset, before and after adjustment for baseline covariates. Use of conventional regression methods in these studies may have resulted in biased parameter estimates, arising from imbalanced covariate distributions in the users and nonusers of SLT. An alternative approach, which has been used widely in the econometric literature, matches exposure or treatment levels on the basis of the propensity score distribution. METHODS Using this approach, we matched current SLT users from the National Longitudinal Study of Adolescent Health with nonusers (496 pairs) and followed them from adolescence into young adulthood for determination of smoking status. RESULTS Prior to matching, the unadjusted risk of becoming a daily smoker was significantly greater for the SLT users compared with nonusers (n = 10,820; range of relative risk = 1.3-2.0, p < .001). However, after pairing individuals on propensity score, we found no evidence for an increased risk of smoking among the SLT users. DISCUSSION Baseline differences in the risk factors for smoking likely account for the association between the two tobacco products.

Genetic and environmental contributions to retrospectively reported DSM-IV childhood attention deficit hyperactivity disorder

BACKGROUND A variety of methodologies and techniques converge on the notion that adults and children with attention deficit hyperactivity disorder (ADHD) have similar deficits, but there is limited knowledge about whether adult retrospective reports reflect similar genetic and environmental influences implicated in childhood ADHD. METHOD DSM-IV ADHD symptoms were collected retrospectively from 3896 young adults participating in the National Longitudinal Study of Adolescent Health. Responses from this genetically informative sample of same- and opposite-sex twins and siblings were used to determine the magnitude of genetic and environmental influences. Possible gender differences in these effects were also examined. The degree of familial specificity of the genetic and environmental influences on the Inattentive and Hyperactive-Impulsive symptom dimensions was also determined. RESULTS Additive genetic effects contributed moderately to DSM-IV Inattentive, Hyperactive-Impulsive and Combined ADHD subtypes (heritability estimates of 0.30-0.38). Individual-specific influences accounted for the remaining proportion of the variance. Both genetic and individual-specific environmental effects contributed to the covariation of Inattentive and Hyperactive-Impulsive symptomologies. CONCLUSIONS Results from our genetic analyses agree with previous findings based on self-assessment of current and retrospectively reported ADHD symptoms in adolescents and adults. Large individual-specific environmental influences as identified here suggest that current questionnaires used for retrospective diagnoses may not provide the most accurate reconstruction of the etiological influences on childhood ADHD in general population samples.

Are smokers receptive to using smokeless tobacco as a substitute

OBJECTIVES Few studies have addressed the feasibility of promoting smokeless tobacco as an alternative for smokers. This study was intended to assess the characteristics and degree to which smokers from California are receptive to using the substitute for harm reduction. METHODS Daily cigarette smokers (n=2995) were selected from the 2005 California Tobacco Survey. Using ordinal logistic regression, four sets of variables (demographics, tobacco use, motivations and intentions to quit smoking) were examined as predictors of the outcome, willingness to use a form of smokeless tobacco perceived to be less harmful than cigarettes. RESULTS A majority of smokers (75.6%) expressed no interest in the tobacco substitute. Contrary to expectation, few of the measures for demographics, tobacco use and motivations to quit smoking were significantly correlated with the outcome. Irrespective of prior use of nicotine replacement therapy, smokers were more receptive if they had previously attempted to quit, or were currently attempting to reduce their consumption of cigarettes. CONCLUSIONS Smokeless tobacco is an unacceptable alternative for most California smokers. But, the expected correlates, notably gender, accounted for minimal variability in SLT receptiveness, an observation that challenges concerns about the products limited appeal to any one group.

Case-control and within-family tests for association between 5HTTLPR and conduct problems in a longitudinal adolescent sample.

Background Several recent studies have reported an association between the serotonin transporter 5HTTLPR (s-allele) and aggression; however, nonreplications have also been reported. Inconsistencies may be explained by gene–environment interactions. Using a large general population sample, we sought to test for an association between 5HTTLPR and conduct problems, and to explore for a possible 5HTTLPR by maltreatment interaction. Methods Using Caucasian adolescents from the genetic-pairs sample of the National Longitudinal Study of Adolescent Health (n=1736), we tested for an association between 5HTTLPR and both a categorical and, separately, a continuous measure of conduct problems using regression analyses while controlling for sex, family effects, and age. We then tested for an association between 5HTTLPR and conduct problems using the within-family test Quantitative Transmission Disequilibrium Test. Analyses were repeated for a measure of adolescence-limited delinquency. Results Results did not support an association between 5HTTLPR and conduct problems or delinquency. The Quantitative Transmission Disequilibrium Test analyses, which account for population stratification, were nonsignificant (F=0.17; P=0.68); introducing maltreatment as a covariate into the model did not affect this association (F=0.17; P=0.68). No association was seen between 5HTTLPR and a measure of adolescence-limited delinquency (F=0.54; P=0.46). Discussion Using two methods in a large general population sample we did not find a significant association between 5HTTLPR and conduct problems. A gene by maltreatment interaction was not supported.

Demographic Profiles of Smokeless Tobacco Users in the U.S.

BACKGROUND Users of smokeless tobacco (chew or snuff) in the U.S. are viewed demographically as being homogeneous. Prior studies have demonstrated such homogeneity in national survey data but have not utilized latent-variable methods. The objective of this study was to determine whether a single group or underlying subgroups best characterize users of smokeless tobacco. METHODS Men aged >17 years who had used smokeless tobacco in the past month (n=4583) were selected from the 2003, 2004, and 2005 National Surveys on Drug Use and Health. A latent-class analysis, conducted in 2008, was based on individual response patterns from six demographic variables and three items pertaining to the use of smokeless tobacco. RESULTS Four latent classes were identified: older chew users (17.2%); younger poly-tobacco users (28.7%); skilled laborers with a high school diploma (27.5%); and educated professionals (26.6%). External validation of these classes indicated that older chew users and younger poly-tobacco users were more likely than the educated professionals to be former and current smokers, respectively. CONCLUSIONS While users of smokeless tobacco in the U.S. are predominantly white men, they are more heterogeneous with respect to education, occupation, and residency than commonly is perceived.