Tobacco smoking and cannabis use in a longitudinal birth cohort: evidence of reciprocal causal relationships.

BACKGROUND: There is evidence of associations between tobacco and cannabis use that are consistent with both a classical stepping-stone scenario that posits the transition from tobacco use to cannabis use ('gateway' effect of tobacco) and with the reverse process leading from cannabis use to tobacco abuse ('reverse gateway' effect of cannabis). The evidence of direct causal relationships between the two disorders is still missing. METHODS: We analysed data from the Christchurch Health and Development Study (CHDS) longitudinal birth cohort using advanced statistical modelling to control for fixed sources of confounding and to explore causal pathways. The data were analysed using both: (a) conditional fixed effects logistic regression modelling; and (b) a systematic structural equation modelling approach previously developed to investigate psychiatric co-morbidities in the same cohort. RESULTS: We found significant (p<0.05) associations between the extent of cannabis use and tobacco smoking and vice versa, after controlling for non-observed fixed confounding factors and for a number of time-dynamic covariate factors (major depression, alcohol use disorder, anxiety disorder, stressful life events, deviant peer affiliations). Furthermore, increasing levels of tobacco smoking were associated with increasing cannabis use (p=0.02) and vice versa (p<0.001) over time. CONCLUSIONS: Our results lend support to the notion of both of 'gateway' and 'reverse gateway' effects. That is, the association between tobacco and cannabis use arises from a reciprocal feedback loop involving simultaneous causation between tobacco use disorder and cannabis use disorder.

Maternal smoking during pregnancy and offspring conduct problems: evidence from 3 independent genetically sensitive research designs.

IMPORTANCE: Several studies report an association between maternal smoking during pregnancy and offspring conduct disorder. However, past research evidences difficulty in disaggregating prenatal environmental influences from genetic and postnatal environmental influences. OBJECTIVE: To examine the relationship between maternal smoking during pregnancy and offspring conduct problems among children reared by genetically related mothers and genetically unrelated mothers. DESIGN, SETTING, AND PARTICIPANTS: The following 3 studies using distinct but complementary research designs were used: The Christchurch Health and Development Study (a longitudinal cohort study that includes biological and adopted children), the Early Growth and Development Study (a longitudinal adoption-at-birth study), and the Cardiff IVF (In Vitro Fertilization) Study (an adoption-at-conception study among genetically related families and genetically unrelated families). Maternal smoking during pregnancy was measured as the mean number of cigarettes per day (0, 1-9, or 10) smoked during pregnancy. Possible covariates were controlled for in the analyses, including child sex, birth weight, race/ethnicity, placement age, and breastfeeding, as well as maternal education and maternal age at birth and family breakdown, parenting practices, and family socioeconomic status. MAIN OUTCOMES AND MEASURE: Offspring conduct problems (age range, 4-10 years) reported by parents or teachers using the behavior rating scales by Rutter and Conners, the Child Behavior Checklist and the Children's Behavior Questionnaire Short Form, and the Strengths and Difficulties Questionnaire. RESULTS: A significant association between maternal smoking during pregnancy and offspring conduct problems was observed among children reared by genetically related mothers and genetically unrelated mothers. Results from a meta-analysis affirmed this pattern of findings across pooled study samples. CONCLUSIONS AND RELEVANCE: Findings across 3 studies using a complement of genetically sensitive research designs suggest that smoking during pregnancy is a prenatal risk factor for offspring conduct problems when controlling for specific perinatal and postnatal confounding factors.

The Beijing Twin Study (BeTwiSt): a longitudinal study of child and adolescent development.

Rates of emotional and behavioral problems among children and adolescents in China are increasing and represent a major public health concern. To investigate the etiology of such problems, including the effects and interplay of genes and environment, the Beijing Twin Study (BeTwiSt) was established. A representative sample of adolescent twins in Beijing (N = 1,387 pairs of adolescent twins, mostly between the ages of 10 and 18 years) was recruited and assessed longitudinally. Data collection included the following: emotional and behavioral problems (e.g., depressive symptoms, anxiety, delinquency, drinking, and smoking); family, peer, and school environments; stress; social and academic competence; cognitive traits (e.g., emotion suppression, rumination, and effortful control); and saliva samples for DNA genotyping and sequencing. The combination of quantitative and molecular genetic approaches and the timeliness of the project, with the sample residing in a region with a rapidly changing economic and cultural climate, are particular strengths of this study. Findings from this study are expected to help understanding of the etiological mechanisms underlying child and adolescent normal and abnormal development in regions undergoing substantial social, cultural, and economic changes.

Girls' Tobacco and Alcohol Use During Early Adolescence: Prediction from Trajectories of Depressive Symptoms Across Two Studies.

Associations between trajectories of depressive symptoms and subsequent tobacco and alcohol use were examined in two samples of girls assessed at age 11.5 (T1), 12.5 (T2), and 13.5 (T3). Two samples were examined to ascertain if there was generalizability of processes across risk levels and cultures. Study 1 comprised a United States-based sample of 100 girls in foster care; Study 2 comprised 264 girls in a United Kingdom community-based sample. Controlling for T1 aggression and T1 substance use, individual variation in intercept and slope of depressive symptoms was associated with tobacco use at T3 in both samples: greater intercept and increases in depressive symptoms increased the risk for T3 tobacco use. A similar pattern of associations was found for alcohol use in Study 1. The replicability of findings for the prediction of tobacco use from trajectories of depressive symptoms suggests potential benefit in identifying girls with elevated depressive symptoms for tobacco use prevention programs prior to the transition to secondary school.

Using a genetically informative design to examine the relationship between breastfeeding and childhood conduct problems.

A number of public health interventions aimed at increasing the uptake of breastfeeding are in place in the United States and other Western countries. While the physical health and nutritional benefits of breastfeeding for the mother and child are relatively well established, the evidence for psychological effects is less clear. This study aimed to examine whether there is an association between breastfeeding and later conduct problems in children. It also considered the extent to which any relationship is attributable to maternally-provided inherited characteristics that influence both likelihood of breastfeeding and child conduct problems. A prenatal cross-fostering design with a sample of 870 families with a child aged 4-11 years was used. Mothers were genetically related or unrelated to their child as a result of assisted reproductive technologies. The relationship between breastfeeding and conduct problems was assessed while controlling for theorised measured confounders by multivariate regression (e.g. maternal smoking, education, and antisocial behaviour), and for unmeasured inherited factors by testing associations separately for related and unrelated mother-child pairs. Breastfeeding was associated with lower levels of conduct disorder symptoms in offspring in middle childhood. Breastfeeding was associated with lower levels of conduct problems even after controlling for observed confounders in the genetically related group, but not in the genetically unrelated group. In contrast, maternal antisocial behaviour showed robust associations with child conduct problems after controlling for measured and inherited confounders. These findings highlight the importance of using genetically sensitive designs in order to test causal environmental influences.

Disentangling prenatal and inherited influences in humans with an experimental design.

Exposure to adversity in utero at a sensitive period of development can bring about physiological, structural, and metabolic changes in the fetus that affect later development and behavior. However, the link between prenatal environment and offspring outcomes could also arise and confound because of the relation between maternal and offspring genomes. As human studies cannot randomly assign offspring to prenatal conditions, it is difficult to test whether in utero events have true causal effects on offspring outcomes. We used an unusual approach to overcome this difficulty whereby pregnant mothers are either biologically unrelated or related to their child as a result of in vitro fertilization (IVF). In this sample, prenatal smoking reduces offspring birth weight in both unrelated and related offspring, consistent with effects arising through prenatal mechanisms independent of the relation between the maternal and offspring genomes. In contrast, the association between prenatal smoking and offspring antisocial behavior depended on inherited factors because association was only present in related mothers and offspring. The results demonstrate that this unusual prenatal cross-fostering design is feasible and informative for disentangling inherited and prenatal effects on human health and behavior. Disentangling these different effects is invaluable for pinpointing markers of prenatal adversity that have a causal effect on offspring outcomes. The origins of behavior and many common complex disorders may begin in early life, therefore this experimental design could pave the way for identifying prenatal factors that affect behavior in future generations.

Twins born following fertility treatment: implications for quantitative genetic studies.

The rate of multiple births is substantially elevated in women who have had assisted reproduction treatment (ART; approximately 26%) compared to the general population ( approximately 1%), and these offspring are usually included in twin studies. Several studies have attempted to identify possible consequences of undergoing ART on the subsequent offspring. However, most studies have only included singleton births. We first examined whether twins born by ART differed from other twins on measures of childhood psychopathology, putative risk factors and correlates, and secondly tested for differences in the degree of twin similarity for available outcome measures. From a population-based twin sample, 101 families with dizygotic (DZ) twins conceived via ART were identified and compared with 1073 naturally conceived (NC) control DZ twin pairs. Analyses performed were (1) univariate and multivariate comparisons of between-group mean differences; and (2) comparison of twin 1-twin 2 correlations between the groups. The groups differed significantly on demographic factors (parental age, family size and social class) and pregnancy variables (smoking during pregnancy and birthweight) but did not differ on family conflict scores or in the frequency of obstetric complications. Family cohesion was higher in the ART group but this was accounted for by demographic factors. For child psychopathology there was a difference between the groups only for teacher-rated ADHD (Attention Deficit Hyperactivity Disorder). Differences were also found between groups for twin correlations. The differences found between ART and NC twins on group means and twin correlations suggest that researchers should be aware that including ART twins may influence results from twin studies.

Distinct patterns of hippocampal formation activity associated with different spatial tasks: a Fos imaging study in rats.

Fos levels were measured in rats trained in one of two qualitatively different spatial memory tasks in a water maze. In one task, ( landmark condition) rats found a submerged platform that was always 25 cm south of a visible landmark, the absolute position of the platform and landmark changing after every trial. In the other task ( place condition), rats swam to a platform that remained in the same absolute position on every session, but changed session to session, with this task relying on the memory of allocentric cues. Despite matched swim times, the landmark condition resulted in higher levels of Fos in a wide range of cortical and subcortical sites, including the hippocampus and its connections. Structural equation modelling revealed two different patterns of hippocampal function. In the allocentric place task there was a significant association between Fos activity in the entorhinal cortices and the hippocampus proper, while in the non-allocentric landmark task this relationship was not present, but was replaced by a connection from the entorhinal cortices to the subiculum. Thus, the two different tasks engage two different modes of hippocampal activity as demonstrated by Fos expression.