The period of in utero development is one of the most critical windows during which adverse intrauterine conditions and exposures may influence the growth and development of the fetus as well as its future postnatal health and behavior. Maternal cigarette smoking during pregnancy remains a relatively common but nonetheless hazardous in utero exposure. Previous studies have associated prenatal smoke exposure with reduced birth weight, poor developmental and psychological outcomes, and increased risk for diseases and behavioral disorders later in life. Researchers are now learning that many of the mechanisms whereby maternal smoke exposure may affect key pathways crucial for proper fetal growth and development are epigenetic in nature. Maternal cigarette smoking during pregnancy has been associated with altered DNA methylation and dysregulated expression of microRNA, but a deeper understanding of the epigenetics of maternal cigarette smoking during pregnancy as well as how these epigenetic changes may affect later offspring health and behavior remain to be elucidated. This review seeks to explore many of the previously described epigenetic alterations associated with maternal cigarette smoking during pregnancy and assesses how such changes may have consequences for both fetal growth and development, as well as later child health, behavior and well-being. We also outline future directions for this new and exciting field of research.

Impulsivity is associated with increased marijuana use and subsequent marijuana-related problems among marijuana users. In addition, single nucleotide polymorphisms (SNPs) in the cannabinoid receptor 1 (CNR1) and fatty acid amide hydrolase (FAAH) genes have been associated with cannabis-related phenotypes. This exploratory study tested whether the association between different aspects of impulsivity and the number of marijuana-related problems among users is explicated by variation in these putative cannabinoidrelated genes. Method: A total of 151 young adult regular marijuana users (used on M = 41.4% of the prior 60 days, SD = 24.3%) provided DNA and completed measures of trait (Barratt Impulsiveness Scale) and behavioral impulsivity (Stop Signal Task and Delay Discounting Questionnaire), as well as a self-report of marijuana-related problems. Three CNR1 and fi ve FAAH SNPs were genotyped, tested for haplotype blocks, and subsequently examined for association with phenotypes described above. Results: CNR1 variation signifi cantly moderated the association between trait-level, but not behavioral, impulsivity and marijuana-related problems, such that the combination of higher trait impulsivity and CNR1 variation was associated with a greater number of marijuana-related problems. In contrast, there were no signifi cant FAAH by impulsivity interactions; however, there was a main effect of FAAH on marijuana-related problems. Conclusions: These fi ndings support an association with CNR1 and FAAH genes and marijuana-related problems among regular marijuana users. CNR1 variation emerged as a moderator of the relationship between trait impulsivity and marijuana problems, thus suggesting that marijuana users with CNR1 risk variants and a higher trait impulsivity are at greater risk for developing marijuanarelated problems and supporting a role for CNR1 in a broader impulsivity phenotype.

BACKGROUND Personalized treatment for psychopathologies, in particular alcoholism, is highly dependent upon our ability to identify patterns of genetic and environmental effects that influence a person’s risk. Unfortunately, array-based whole genome investigations into heritable factors that explain why one person becomes dependent upon alcohol and another does not, have indicated that alcohol’s genetic architecture is highly complex. That said, uncovering and interpreting the missing heritability in alcohol genetics research has become all the more important, especially since the problem may extend to our inability to model the cumulative and combinatorial relationships between common and rare genetic variants. As numerous studies begin to illustrate the dependency of alcohol pharmacotherapies on an individual’s genotype, the field is further challenged to identify new ways to transcend agnostic genomewide association approaches. We discuss insights from genetic studies of alcohol related diseases, as well as issues surrounding alcohol’s genetic complexity and etiological heterogeneity. Finally, we describe the need for innovative systems-based approaches (Systems Genetics) that can provide additional statistical power that can enhance future gene-finding strategies and help to identify heretofore-unrealized mechanisms that may provide new targets for prevention/treatments efforts. Emerging evidence from early studies suggest that Systems Genetics has the potential to organize our neurological, pharmacological, and genetic understanding of alcohol dependence into a biologically plausible framework that represents how perturbations across evolutionarily robust biological systems determine susceptibility to alcohol dependence.