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Aims: To determine (1) the prospective associations of conduct problems during early adolescence with tobacco, alcohol and cannabis use in young adulthood and (2) to what extent these associations are due to overlapping genetic versus environmental influences., Design: A prospective twin study using biometric twin modelling., Setting: Finland., Participants: A total of 1847 Finnish twins (943 males and 904 females) were interviewed in early adolescence, 73% of whom (n = 1353, 640 males and 713 females) were retained in young adulthood., Measurements: Symptom counts of conduct disorder (CD) criteria were obtained from a semi-structured clinical interview in early adolescence [age 14-15 years, mean = 14.2, standard deviation (SD) = 0.15]. Frequency of alcohol, tobacco and cannabis use was obtained from a semi-structured clinical interview in young adulthood (age 19.9-26.6 years, mean = 22.4, SD = 0.7)., Findings: We found modest to moderate phenotypical correlations (r = 0.16-0.35) between early adolescent CD symptoms and substance use in young adulthood. In males, the phenotypical correlations of CD symptoms with all three substance use variables are explained largely by overlapping genetic influences. In females, overlapping shared environmental influences predominantly explain the phenotypical correlation between CD symptoms and tobacco and cannabis use., Conclusions: Conduct disorder symptoms in early adolescence appear to moderately predict substance use in early adulthood. In males, genetic influences seem to be most important in explaining the relationship between conduct disorder symptoms and substance use whereas in females, shared environmental influences seem to be most important., (© 2016 Society for the Study of Addiction.)

Aims: To examine whether early onset of tobacco or alcohol use, and continued use of tobacco or alcohol in early adolescence, are related to a higher likelihood of developing a cannabis use disorder during adolescence., Design and Setting: Data were used from four consecutive assessment waves of the TRacking Adolescents' Individual Lives Survey (TRAILS), a general Dutch population study. TRAILS is an ongoing longitudinal study that will follow the same group of adolescents from the ages of 10 to 24 years., Participants: The sample consisted of 1108 (58% female) adolescents (mean ages at the four assessment waves are 11.09, 13.56, 16.27 and 19.05 years, respectively), Measurements: Cannabis use disorders were assessed using the Composite International Diagnostic Interview 3.0 (CIDI). Adolescent tobacco and alcohol use were assessed using self-report questionnaires., Findings: Early-onset tobacco use [odds ratio (OR) = 1.82, confidence interval (CI) = 1.05-3.14, P < 0.05], but not early-onset alcohol use (OR = 1.33, CI = 0.84-2.12, P > 0.05), was associated with a higher likelihood of developing a cannabis use disorder. Similarly, adolescents who reported continued use of tobacco (OR = 2.47, CI = 1.02-5.98, P < 0.05), but not continued use of alcohol (OR = 1.71, CI = 0.87-3.38, P > 0.05), were more likely to develop a cannabis use disorder., Conclusions: Early-onset and continued tobacco use appear to predict the development of a cannabis use disorder in adolescence, whereas early onset and continued alcohol use do not., (© 2013 Society for the Study of Addiction.)

Background: Few studies have investigated physiological stress (re)activity in relation to substance use, especially in adolescents. Using substances is one way to stimulate physiological arousal, therefore inherent hypo-arousal may be associated with substance use in adolescents. The purpose of this study was to examine the relation of autonomic nervous system (ANS) activity with alcohol and tobacco use in adolescents., Methods: ANS activity and perceived stress during a social stress procedure were examined in relation to substance use. 275 Dutch adolescents from a general population study provided complete data. Heart rate was recorded continuously during a pre-task rest period, a stressful task period and a post-task recovery period. Alcohol and tobacco use were self-reported., Results: Adolescents who consumed a medium and high number of alcoholic drinks per week (more than two) exhibited lower heart rates during the entire stress procedure as compared to those who consumed a low number of alcoholic drinks. Adolescents who smoked every day portrayed blunted heart rate reactivity to stress as compared to adolescents who smoked less frequently or not at all. Perceived stress was not related to alcohol or tobacco use., Conclusions: Overall lower heart rate in adolescents who drank more and blunted heart rate reactivity to stress in those who used tobacco every day may indicate inherent hypo-arousal of the ANS system in those vulnerable to use substances more often. These adolescents may actively seek out substances in order to achieve a more normalized state of arousal., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Objective: This study examines the association between neurocognitive functioning and tobacco smoking in adolescence., Method: Data from three measurements of the longitudinal Tracking Adolescents' Individual Lives Survey (TRAILS), a large regional population-based cohort study of Dutch adolescents, were used. The first measurement took place in 2001-2002 (T1) when participants were age 11, with two follow-up measurements (2003-2004 and 2005-2007; T2 and T3, respectively). A total of 1,797 adolescents participated in all three waves. At T1, they performed a selection of tasks from the Amsterdam Neuropsychological Tasks program (De Sonneville, 1999), which enabled the assessment of the main aspects of neurocognitive functioning. Smoking was assessed with a self-report questionnaire at T1, T2, and T3. In the multivariate analyses we controlled for gender, age, socioeconomic status (SES) and baseline speed., Results: Multivariate logistic regression analyses showed that poor sustained attention increased the likelihood that the adolescent would initiate smoking between T1 and T2. Low inhibition of prepotent responses increased the likelihood of smoking initiation between T1 and T3. An increased ability to inhibit biased response tendencies reduced the likelihood of being a daily smoker at T2. Poor sustained attention increased the likelihood of being a daily smoker at T3., Conclusion: Poor sustained attention and low inhibition predicted adolescent smoking. However, the proportion of the variance in smoking risk accounted for by these neurocognitive predictors proved to be small. Thus, although neurocognitive functioning is related to adolescent smoking, it seems to explain only a small part of why adolescents initiate and continue smoking.

We investigated genetic and environmental influences common to adolescent externalizing behavior (at age 12), smoking (at age 14) and initiation of drug use (at age 17) using the FinnTwin12 cohort data. Multivariate Cholesky models were fit to data from 737 monozygotic and 722 dizygotic twin pairs. Heritability of externalizing behavior was 56%, that of smoking initiation/amount 20/32%, and initiation of drug use 27%. In the best-fitting model common environmental influences explained most of the covariance between externalizing behavior and smoking initiation (69%) and amount (77%). Covariance between smoking initiation/amount and drug use was due to additive genetic (42/22%) and common environmental (58/78%) influences. Half of the covariance between externalizing behavior and drug use was due to shared genetic and half due to the environments shared by co-twins. Using a longitudinal, prospective design, our results indicate that early observed externalizing behavior provides significant underlying genetic and environmental influences common to later substance use, here manifested as initiation of drug use in late adolescence.

Purpose: There is substantial research linking tobacco and alcohol use to subsequent cannabis use, yet the specificity of this relationship is still under debate. The aim of this study was to examine which substance use model--the gateway hypothesis, the common liability (CL) model and/or the route of administration model--best explains the relationship between early onset of tobacco and alcohol use and subsequent cannabis use initiation., Methods: We used data from 2,113 (51% female) Dutch adolescents who participated in three consecutive assessment waves (mean age: 11.09, 13.56, and 16.27 years, respectively) of the TRacking Adolescents' Individual Lives Survey study. (Pre)adolescent cannabis, tobacco and alcohol use was assessed using the Youth Self-Report and a TRacking Adolescents' Individual Lives Survey developed questionnaire., Results: We found that, during adolescence, early onset of tobacco use does not pose a significantly higher risk of initiating cannabis use than early onset alcohol use. Therefore, we can rule out the route of administration model. Moreover, we found that adolescents who reported early onset comorbid use of both tobacco and alcohol have a higher likelihood to initiate cannabis use than adolescents who have tried either tobacco or alcohol. The gateway hypothesis is not broad enough to explain this finding. Therefore, the CL model best predicts our findings., Conclusion: Future research on adolescent cannabis initiation should focus on testing the robustness of the CL model. Furthermore, identifying adolescents who use both tobacco and alcohol, before the age of 13, may help to curtail the onset of cannabis use., (Copyright © 2011 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Objective: This study examined (a) the predictive value of observed versus reported measures of impulsivity on the onset of cannabis use and determined if lifetime tobacco and cannabis users can be differentiated by their level of impulsivity and (b) the predictive value of observed versus reported measures of impulsivity on repeated cannabis use and determined if repeated tobacco and cannabis users can be differentiated by their level of impulsivity., Method: The present study involves 667 (50.5% female) adolescents assessed at two time points of the TRacking Adolescents' Individual Lives Survey (TRAILS). Adolescents in our study participated in the Bangor Gambling Task (BGT), as well as completed self-report questionnaires assessing cannabis use behavior (Mage = 16.11 years) and the Behavioral Inhibition System (BIS)/Behavioral Activation System (BAS) questionnaire (Mage = 13.56 years)., Results: Higher levels of BAS functioning increased the likelihood that adolescents would ever use substances such as tobacco or cannabis during their lifetime. In contrast, low BIS functioning increased the likelihood of repeated cannabis use. Repeated tobacco users did not significantly differ from lifetime users by their BIS functioning. The BGT measures were not significant in relation to lifetime or repeated use of cannabis or tobacco., Conclusions: High BAS seems to be more important for experimental substance use, whereas low BIS seems to be more important for progression into regular cannabis use specifically. In contrast to the BIS/BAS, our laboratory test of impulsivity, the BGT, is not correlated with early-onset tobacco/cannabis use. Furthermore, the BGT is not correlated with the BIS/BAS measures.

Aims: To study the prospective relationship between maternal smoking during pregnancy (MSP) and behavioral problems, heavy alcohol use, daily smoking, and ever use of cannabis in the offspring, and to assess the role of confounding and mediating factors in a systematic way., Methods: Population-based cohort study of 2,230 respondents, starting in 2001 when respondents were around the age of 11 years, and two follow-up measurements at intervals of about 2.5 years (response rates of 96.0 and 81.4%)., Results: Almost one third of the respondents' mothers had smoked tobacco during pregnancy. These respondents were at an increased risk for all outcomes except internalizing problems (significant odds ratios ranged from 1.40 to 2.97). The successive models showed that the potential confounding factors reduced the strength of all relationships. In the full model, the strongest relationship was found for mothers who smoked more than 10 cigarettes a day during pregnancy and daily smoking in early adolescence (odds ratio: 1.56), but none of the relationships were statistically significant., Conclusions: MSP is a marker for future behavioral outcomes in the offspring, but reducing the prevalence of MSP is unlikely to make a meaningful contribution to the prevention of these problems in adolescents., (Copyright © 2011 S. Karger AG, Basel.)

We examined whether externalizing problem behaviors (hyperactivity-impulsivity, aggressiveness, and inattention) predict illicit drug use independently, or whether their associations with drug use are mediated through cigarette smoking. We used a prospective longitudinal design within the FinnTwin12-17 study among Finnish adolescents with baseline at age 12 and follow-up surveys at ages 14 and 17. Path models were conducted with Mplus and included 1992 boys and 2123 girls. The outcome was self-reported ever use of cannabis or other illicit drugs at age 17. The predictors were: externalizing behaviors (hyperactivity-impulsivity, aggressiveness, and inattention) assessed by teachers and parents (age 12) and self-reported cigarette smoking (age 14). The findings differed across behavior studied. The association of hyperactivity-impulsivity with drug use was mostly mediated through earlier cigarette smoking. Concerning aggressiveness and inattention, the results were different among girls than boys. Among girls no significant mediation occurred, whereas among boys more consistent evidence on mediation was seen. Consistently in all models, the direct association of early cigarette smoking on drug use was strong and highly significant. We conclude that the associations of externalizing problem behaviors with illicit drug use are partially mediated through cigarette smoking. Although interventions targeting externalizing problem behaviors may protect adolescents from early onset smoking and subsequently experimenting with drugs, interventions to prevent cigarette smoking initiation are also important in reducing risk of later drug use.

Objective: Among Finnish adolescent twins, we compared (a) a model that describes a direct impact of liability to tobacco use on cannabis and other illicit drug use with (b) a model that included a shared underlying liability for these substances. Furthermore, the extent to which genetic and environmental influences contribute to the covariation between liabilities to use these substances was examined., Method: Tobacco and illicit drug use were assessed at age 17.5 years. Twin data on 3,744 individuals were analyzed using standard biometrical methods. Two alternative multivariate models were fi t and compared with Mx, a statistical program for genetic model fitting., Results: The multivariate model, including a direct impact of the initiation of tobacco use on illicit drug use, provided the best fit to the data. In this model, the total variation in the initiation of illicit drugs was decomposed to genetic factors (32%), common environmental factors (20%), unique environmental factors (8%), and a component due to initiation of smoking (40%). Most variation in the progression of illicit drug use was the result of initiation of smoking and illicit drug use (83%)., Conclusions: Liability to initiate smoking directly affects illicit drug use in our best-fitting model. Our findings suggest that several common genetic influences may be related to tobacco use and illicit drugs but that a search for specific genes underlying illicit drug use is justifi ed as well. Such specific genes may hold a key to understanding biological vulnerabilities that lead to illicit drug use, which could aid in the development of targeted interventions.

Objective: To examine externalizing behavior problems and cigarette smoking as predictors of subsequent cannabis use., Method: Dutch adolescents (N = 1,606; 854 girls and 752 boys) from the TRacking Adolescents' Individual Lives Survey (TRAILS) ongoing longitudinal study were examined at baseline (ages 10-12 [T1]) and at two follow-up assessments (ages 12-15 [T2] and 15-18 [T3]). The analysis focused on DSM-IV externalizing behavior (conduct, attention deficit hyperactivity, and oppositional) problems at T1, assessed by the Youth Self Report and the Child Behavior Check List, on self-reported ever smoking at T2, and on cannabis use at T3., Results: All associations of parent-rated externalizing behavior problems with cannabis were mediated by earlier smoking. Considering self-reported problems, none of these associations with cannabis were mediated by smoking, except the influence of self-reported conduct problems in girls. Interestingly, even after adjusting for externalizing problems, earlier smoking independently and consistently predicted cannabis use. The adjusted odds ratios for smoking varied in boys from 4.8 to 5.2 (ever) from 10 to 12 (daily) and from 22 to 23 (early-onset) whereas in girls from 4.9 to 5.0, 5.6 to 6.1, and 27 to 28, respectively (p <.001 for all)., Conclusions: Our findings challenge the view that externalizing behavior problems directly predict cannabis initiation. Such associations were inconsistent across informants and sexes and were often mediated by earlier smoking. Early smoking onset is a powerful predictor of later cannabis initiation independent of preceding externalizing behavior problems. Although externalizing behavior problems are important as a starting point for substance use trajectories, early-onset smoking should be identified as an important marker of cannabis use risk.

Aims: We examined within a prospective longitudinal study whether cortisol levels were associated with smoking or drinking behaviours, taking parental substance use into account., Design: The influence of parental substance use on cortisol levels of their adolescent offspring at age 10-12 years was examined. Next, cortisol levels of adolescents who initiated smoking or drinking at the first data collection (age 10-12) were compared to non-users. Finally, we examined whether cortisol levels could predict new onset and frequency of smoking and drinking 2 years later., Setting and Participants: First and second assessment data of the TRacking Adolescents' Individual Lives Survey (TRAILS) were used, including 1768 Dutch adolescents aged 10-12 years, who were followed-up across a period of 2 years., Measurements: Cortisol was measured in saliva samples at awakening, 30 minutes later, and at 8 p.m. at age 10-12. Self-reported substance use at age 10-12 and 13-14, and parental self-reported substance use were used., Findings: Only maternal substance use was related to slightly lower adolescent cortisol levels at 8 p.m. Both maternal and paternal substance use were associated with adolescent smoking and drinking at age 13-14, although fathers' use only predicted the amount used and not the chance of ever use. Finally, higher cortisol levels were related moderately to current smoking and future frequency of smoking, but not to alcohol use., Conclusions: In a general population, parental heavy substance use does not seem to affect cortisol levels consistently in their offspring. We found some evidence for higher, instead of lower, hypothalamic-pituitary-adrenal axis activity as a predictor of smoking in early adolescence.

Interest in fetal origins of adverse offspring outcomes has grown extensively in the last decade. This has resulted in many published studies focusing on exposure in utero to substances and human offspring outcomes. Exposure to maternal substance use in pregnancy is believed to be a preventable hazard, and is therefore a main issue for public health concern and policy. However, an important question in human studies remains whether prenatal substance use exposure has an aetiological role in pathways to adverse developmental and behavioural outcomes via teratological effects. Recent insights and developments in research methodology will aid the adequate and more refined testing of associations between prenatal substance use and offspring outcomes. In particular, novel approaches could assist in disentangling the exposure to substance effects from correlated risk factors. The purpose of this manuscript is therefore to provide an overview of methodological issues involved in studies that focus on the association between maternal substance use during pregnancy and offspring's outcomes, to describe novel approaches to test these associations, and present some examples of new and well-designed studies and discuss their findings.

Background: While temperamental characteristics have been related to the onset of cannabis use, it is not clear at what point(s) along the trajectory from early onset of tobacco use (EOT) to early onset of cannabis use (EOC) these characteristics exert their impact. This study examined if (1) temperamental characteristics predispose to EOT that on its turn predisposes to EOC, and (2) temperament moderates the importance of EOT on the progression to EOC., Methods: Data from 1848 (83%) participants in the TRacking Adolescents' Individual Lives Survey (TRAILS), a prospective population study of Dutch adolescents, were analyzed. We used parent-reports on the Early Adolescent Temperament Questionnaire to assess the dimensions of high-intensity pleasure, frustration, effortful control, shyness and fearfulness at age 10-12. EOT and EOC were defined as use at least once before the ages of 12 and 13 years, respectively, assessed by means of self-reports. We performed mediation and moderation analyses in Mplus., Results: High levels of high-intensity pleasure predisposed to entrance in the trajectory from EOT to EOC. Once tobacco use had been initiated at early age, low levels of shyness and high levels of high-intensity pleasure increased the risk of progression to EOC., Conclusions: Besides a common liability for EOT and EOC based on temperament, the risk of transition from tobacco to cannabis use is modified by temperamental characteristics. Differences in interplay with other risk factors may explain the impact of temperament on distinct points along the substance use trajectory.

Persistent cigarette smoking is associated with significant morbidity and mortality. Correlates of difficulty quitting smoking include psychopathology, such as major depressive disorder, and problems with other substances, such as alcoholism. In addition, socio-demographic risk (e.g. poverty) and protective (e.g. living in a region with stringent tobacco laws) influences can modify risk for persistent cigarette smoking. Using data on 17,919 individuals with a lifetime history of smoking 100 or more cigarettes, from a nationally representative U.S. sample, we examine the constellation of risk and protective factors that correlate with smoking cessation (defined as remaining smoke-free in the past 12 months) across four cohorts: young (18-31 years), intermediate-aged (32-43 years), middle-aged (44-60 years) and older (61-99 years) adults. Using survival analyses, we demonstrate that in addition to a history of DSM-IV nicotine dependence, which is negatively associated with smoking cessation, living below the poverty line is also associated with persistent smoking across all age cohorts. Residents over the age of 31 years living on the U.S. West Coast are less likely to be persistent smokers as well. Major depressive disorder is associated with persistent smoking, but interestingly, only in middle-aged and older adults. Alcoholism and a family history of substance use problems are both correlated with persistent smoking but only in older adults. Here, we find evidence for psychopathology that may hinder successful quit attempts during the developmental period when a majority of quit attempts are made (early to mid-40's). However, our analyses also highlight the important benefits of effective tobacco legislation on the U.S. West Coast and urge policy makers to actively consider addressing issues surrounding tobacco taxation and the impact of poverty on tobacco use, in addition to the risks posed by co-occurring psychiatric problems and other substance use disorders.

Background: Some evidence suggests that prenatal exposure to maternal smoking contributes to the etiology of Attention-Deficit/Hyperactivity Disorder (ADHD). The present study tested an intervention targeting disruptive behavior to establish whether exposure to maternal smoking during pregnancy predicts intervention failure in elementary schoolchildren., Methods: Five hundred and eight elementary schoolchildren were followed from ages 7 to 11. At ages 8 and 9, they were randomly assigned to a control condition, or to a two-year universal classroom-based intervention targeting disruptive behavior. Measures included maternal reports of smoking during pregnancy, teacher-rated symptoms of ADHD from ages 7 to 9 years, and children's self-report of experimentation with smoking at ages 10 and 11 years., Results: At age 7, prenatally exposed children had higher ADHD symptom scores. The intervention did not affect the course of their ADHD symptoms and the probability of early-onset experimentation with smoking. Among non-exposed children, the intervention positively affected the course of ADHD symptoms, and reduced the probability of early-onset experimentation with smoking., Conclusions: Prenatally exposed children are most prone to follow a path of high levels of ADHD symptoms and associated elevated risk for early-onset experimentation with smoking, which is unreceptive to a universal preventive intervention. In these children, the developmental course of ADHD symptoms seems to have been influenced by their prenatal exposure to maternal smoking. Future research should further explore whether prenatal smoking is a proxy measure that indexes another risk factor, or a causal factor for adverse developmental outcomes.

Teratological investigations have demonstrated that agents that are relatively harmless to the mother may have significant negative consequences to the fetus. Among these agents, prenatal alcohol, nicotine or cannabis exposure have been related to adverse offspring outcomes. Although there is a relatively extensive body of literature that has focused upon birth and behavioral outcomes in newborns and infants after prenatal exposure to maternal smoking, drinking and, to a lesser extent, cannabis use, information on neurobehavioral and cognitive teratogenic findings beyond these early ages is still quite limited. Furthermore, most studies have focused on prenatal exposure to heavy levels of smoking, drinking or cannabis use. Few recent studies have paid attention to low or moderate levels of exposure to these substances. This review endeavors to provide an overview of such studies, and includes animal findings and potential mechanisms that may explain the mostly subtle effects found on neurobehavioral and cognitive outcomes. It is concluded that prenatal exposure to either maternal smoking, alcohol or cannabis use is related to some common neurobehavioral and cognitive outcomes, including symptoms of ADHD (inattention, impulsivity), increased externalizing behavior, decreased general cognitive functioning, and deficits in learning and memory tasks.

Objective: To examine externalizing behavior problems and cigarette smoking as predictors of subsequent cannabis use. Method: Dutch adolescents (N = 1,606; 854 girls and 752 boys) from the TRacking Adolescents' Individual Lives Survey (TRAILS) ongoing longitudinal study were examined at baseline (ages 10-12 [T1]) and at two follow-up assessments (ages 12-15 [T2] and 15-18 [T3]). The analysis focused on DSM-IV externalizing behavior (conduct, attention deficit hyperactivity, and oppositional) problems at T1, assessed by the Youth Self Report and the Child Behavior Check List, on self-reported ever smoking at T2, and on cannabis use at T3. Results: All associations of parent-rated externalizing behavior problems with cannabis were mediated by earlier smoking. Considering self-reported problems, none of these associations with cannabis were mediated by smoking, except the influence of self-reported conduct problems in girls. Interestingly, even after adjusting for externalizing problems, earlier smoking independently and consistently predicted cannabis use. The adjusted odds ratios for smoking varied in boys from 4.8 to 5.2 (ever) from 10 to 12 (daily) and from 22 to 23 (early-onset) whereas in girls from 4.9 to 5.0, 5.6 to 6.1, and 27 to 28, respectively (p less than 0.001 for all). Conclusions: Our findings challenge the view that externalizing behavior problems directly predict cannabis initiation. Such associations were inconsistent across informants and sexes and were often mediated by earlier smoking. Early smoking onset is a powerful predictor of later cannabis initiation independent of preceding externalizing behavior problems. Although externalizing behavior problems are important as a starting point for substance use trajectories, early-onset smoking should be identified as an important marker of cannabis use risk. (Contains 4 tables.)