The momentum of genomic science will carry it far into the future and into the heart of research on typical and atypical behavioral development. The purpose of this paper is to focus on a few implications and applications of these advances for understanding behavioral development. Quantitative genetics is genomic and will chart the course for molecular genomic research now that these two worlds of genetics are merging in the search for many genes of small effect. Although current attempts to identify specific genes have had limited success, known as the missing heritability problem, whole-genome sequencing will improve this situation by identifying all DNA sequence variation including rare variants. Because the heritability of complex traits is caused by many DNA variants of small effect in the population, polygenic scores that are composites of hundreds or thousands of DNA variants will be used by developmentalists to predict children’s genetic risk and resilience. The most far-reaching advance will be the widespread availability of whole-genome sequence for children, which means that developmentalists would no longer need to obtain DNA or to genotype children in order to use genomic information in research or in the clinic.
quantitative genetics; molecular genetics; DNA; missing heritability; whole-genome sequencing
Recent evidence suggests that impulsivity and sensation seeking are not stable risk factors for substance use among adolescents and early adults but rather that they undergo significant developmental maturation and change. Further, developmental trends of both personality facets may vary across individuals. In the current investigation, we used longitudinal data from ages 15-26 on 5,632 individuals drawn from the offspring generation of the National Longitudinal Survey of Youth (CNLSY) to examine whether inter-individual differences in intra-individual change in impulsivity and sensation seeking predicted the escalation of alcohol, marijuana, and cigarette use in adolescence and early adulthood. Latent growth curve models revealed significant individual differences in rates of change in both personality and substance use. Most importantly, age-related changes in personality were positively associated with individual differences in substance use change. Individuals who declined more slowly in impulsivity increased in alcohol, marijuana, and cigarette use more rapidly, whereas individuals who declined more slowly in sensation seeking increased more rapidly in alcohol use only. Although risk for substance use across the population may peak during adolescence and early adulthood, this risk may be highest among those who decline more gradually in impulsivity.
Impulsivity; Sensation Seeking; Substance Use; Correlated Changes; Latent Growth Curve Modeling
In this study we investigated the development of the hypothalamic–pituitary–adrenal (HPA) axis in 21 group-living rhesus monkeys infants that were physically abused by their mothers in the first few months of life and in 21 nonabused controls. Cortisol and adrenocorticotropin hormone (ACTH) responses to a corticotropin-releasing hormone (CRH) challenge were assessed at 6-month intervals during the subjects’ first 3 years of life. Abused infants exhibited greater cortisol responses to CRH than controls across the 3 years. Abused infants also exhibited blunted ACTH secretion in response to CRH, especially at 6 months of age. Although there were no significant sex differences in abuse experienced early in life, females showed a greater cortisol response to CRH than males at all ages. There were no significant sex differences in the ACTH response to CRH, or significant interactions between sex and abuse in the ACTH or cortisol response. Our findings suggest that early parental maltreatment results in greater adrenocortical, and possibly also pituitary, responsiveness to challenges later in life. These long-term alterations in neuroendocrine function may be one the mechanisms through which infant abuse results in later psychopathologies. Our study also suggests that there are developmental sex differences in adrenal function that occur irrespective of early stressful experience. The results of this study can enhance our understanding of the long-term effects of child maltreatment as well as our knowledge of the development of the HPA axis in human and nonhuman primates.
Allostatic load is the “wear and tear” of the body resulting from the repeated activation of compensatory physiological mechanisms in response to chronic stress. Allostatic load can significantly affect the aging process and result in reduced longevity, accelerated aging, and impaired health. Although low socioeconomic status is associated with high allostatic load during aging, the effects of status-related psychosocial stress on allostatic load are often confounded by lifestyle variables. Chronic psychosocial stress associated with low dominance rank in nonhuman primates represents an excellent animal model with which to investigate allostatic load and aging in humans. Research conducted with free-ranging rhesus monkeys suggests that female reproduction can also be a source of stress and allostatic load. Female reproduction is associated with increased risk of mortality and hyperactivation of the hypothalamic–pituitary–adrenal axis. Reproduction is especially stressful and costly for aging females of low rank. Although many indicators of body condition and neuroendocrine and immune function are influenced by aging, there are marked and stable individual differences among aging females in body condition, plasma cortisol responses to stress, and cytokine responses to stress. These differences are consistent with the hypothesis that there are strong differences in chronic stress among individuals, and that allostatic load resulting from chronic stress affects health during aging. Comparisons between captive and free-ranging rhesus monkey populations may allow us to understand how differences in environmental stress and allostatic load affect rates of aging, and how these in turn translate into differences in longevity and health.
Using behavioral and blood oxygen level dependent (BOLD) response indices through functional magnetic resonance imaging (fMRI), the current study investigated whether youths with disruptive behavior disorders (conduct disorder and oppositional defiant disorder) plus psychopathic traits (DBD + PT) show aberrant sensitivity to eye gaze information generally and/or whether they show particular insensitivity to eye gaze information in the context of fearful expressions. The participants were 36 children and adolescents (ages 10–17 years); 17 had DBD + PT and 19 were healthy comparison subjects. Participants performed a spatial attention paradigm where spatial attention was cued by eye gaze in faces displaying fearful, angry, or neutral affect. Eye gaze sensitivity was indexed both behaviorally and as BOLD response. There were no group differences in behavioral response: both groups showed significantly faster responses if the target was in the congruent spatial direction indicated by eye gaze. Neither group showed a Congruence × Emotion interaction; neither group showed an advantage from the displayer’s emotional expression behaviorally. However, the BOLD response revealed a significant Group × Congruence × Emotion interaction. The comparison youth showed increased activity within the dorsal endogenous orienting network (superior parietal lobule and inferior parietal sulcus) for fearful congruent relative to incongruent trials relative to the youth with DBD + PT. The results are discussed with reference to current models of DBD + PT and possible treatment innovations.
This study examined genetic and environmental influences on associations
among marital conflict about the child, parental monitoring, sibling
relationship negativity, and peer delinquency during adolescence and initiation
of illegal drug use by young adulthood. The sample comprised data collected
longitudinally from same-sex sibling pairs and parents when the siblings were
10–18 years old (M = 14.5 and 12.9 years for
Child 1 and Child 2, respectively) and 20–35 years old
(M = 26.8 and 25.5 years for Child 1 and Child 2,
respectively). Findings indicate four factors that explain the initiation of
illegal drug use: two shaped by genetic influences and two shaped by
environments shared by siblings. The two genetically shaped factors probably
have distinct mechanisms: one a child-initiated coercive process in the family
and the other parent and peer processes shaped by the child’s
disclosure. The environmentally influenced factors seem distinctively shaped by
poor parental monitoring of both sibs and the effects of siblings on each
Researchers studying longitudinal relationships among multiple problem behaviors sometimes characterize autoregressive relationships across constructs as indicating “protective” or “launch” factors or as “developmental snares.” These terms are used to indicate that initial or intermediary states of one problem behavior subsequently inhibit or promote some other problem behavior. Such models are contrasted with models of “general deviance” over time in which all problem behaviors are viewed as indicators of a common linear trajectory. When fit of the “general deviance” model is poor and fit of one or more autoregressive models is good, this is taken as support for the inhibitory or enhancing effect of one construct on another. In this paper, we argue that researchers consider competing models of growth before comparing deviance and time-bound models. Specifically, we propose use of the free curve slope intercept (FCSI) growth model (Meredith & Tisak, 1990) as a general model to typify change in a construct over time. The FCSI model includes, as nested special cases, several statistical models often used for prospective data, such as linear slope intercept models, repeated measures multivariate analysis of variance, various one-factor models, and hierarchical linear models. When considering models involving multiple constructs, we argue the construct of “general deviance” can be expressed as a single-trait multimethod model, permitting a characterization of the deviance construct over time without requiring restrictive assumptions about the form of growth over time. As an example, prospective assessments of problem behaviors from the Dunedin Multidisciplinary Health and Development Study (Silva & Stanton, 1996) are considered and contrasted with earlier analyses of Hussong, Curran, Moffitt, and Caspi (2008), which supported launch and snare hypotheses. For antisocial behavior, the FCSI model fit better than other models, including the linear chronometric growth curve model used by Hussong et al. For models including multiple constructs, a general deviance model involving a single trait and multimethod factors (or a corresponding hierarchical factor model) fit the data better than either the “snares” alternatives or the general deviance model previously considered by Hussong et al. Taken together, the analyses support the view that linkages and turning points cannot be contrasted with general deviance models absent additional experimental intervention or control.
Home baseline and laboratory stressor (Trier Social Stress Test for Children) measures of salivary cortisol were obtained from 82 participants (40 girls) aged 9, 11, 13, and 15 years. Measures of pubertal development, self-reported stress, parent reports of child depressive symptoms and fearful temperament, and cardiac measures of sympathetic and parasympathetic activity were also obtained. Significant increases in the home cortisol baselines were found with age and pubertal development. Cortisol stress reactivity differed by age group with 11-year-olds and 13-year-old boys showing blunted reactivity and 9-year-olds, 13-year-old girls, and 15-year-olds showing significant cortisol reactions. Cortisol reactivity correlated marginally with sexual maturation. Measures of sympathetic activity revealed increased sympathetic modulation with age. Higher sympathetic tone was associated with more fearful temperament, whereas greater cortisol reactivity was associated with more anxious and depressed symptoms for girls. The importance of these findings for the hypothesis that puberty-associated increases in hypothalamic–pituitary–adrenal axis activity heightens the risk of psychopathology is discussed.
We used a longitudinal twin design to examine selection effects of personality traits at age 11 on high-risk environmental contexts at age 14, and the extent to which these contexts mediated risk for substance abuse at age 17. Socialization at age 11—willingness to follow rules and endorse conventional values—predicted exposure to contextual risk at age 14. Contextual risk partially mediated the effect of socialization on substance abuse, though socialization also had a direct effect. In contrast, boldness at age 11—social engagement and assurance, thrill-seeking, and stress resilience— also predicted substance abuse directly, but was unrelated to contextual risk. There was substantial overlap in the genetic and shared environmental influences on socialization and contextual risk, and genetic risk in socialization contributed to substance abuse indirectly via increased exposure to contextual risk. This suggests that active gene-environment correlations related to individual differences in socialization contributed to an early, high-risk developmental trajectory for adolescent substance abuse. In contrast, boldness appeared to index an independent and direct genetic risk factor for adolescent substance abuse.
Biological parents pass on genotypes to their children, as well as provide home environments that correlate with their genotypes; thus, the association between the home environment and children's temperament can be genetically (i.e. passive gene-environment correlation) or environmentally mediated. Furthermore, family environments may suppress or facilitate the heritability of children's temperament (i.e. gene-environment interaction). The sample comprised 807 twin pairs (M age = 7.93 years) from the longitudinal Wisconsin Twin Project. Important passive gene-environment correlations emerged, such that home environments were less chaotic for children with high Effortful Control, and this association was genetically mediated. Children with high Extraversion/Surgency experienced more chaotic home environments, and this correlation was also genetically mediated. In addition, heritability of children's temperament was moderated by home environments, such that Effortful Control and Extraversion/Surgency were more heritable in chaotic homes, and Negative Affectivity was more heritable under crowded or unsafe home conditions. Modeling multiple types of gene-environment interplay uncovered the complex role of genetic factors and the hidden importance of the family environment for children's temperament and development more generally.
Although the sensitization hypothesis is fundamental to process-oriented explanations of the effects of marital conflict on children, few longitudinal tests of the theory’s propositions have been conducted. This prospective, longitudinal study (n = 297 families) used HLM to assess changes in dimensions of responding to conflict (i.e., emotional, cognitive, behavioral) for three consecutive years in youth between the ages of 8 and 19 years. Moreover, to test the notion of sensitization, analyses examined whether change in marital conflict predicted change in children’s responding across middle childhood and adolescence. Supporting the sensitization hypothesis, increases in exposure to hostile marital conflict were associated with increases in children’s negative emotionality, threat, self blame, and skepticism about resolution. With a few exceptions, effects were largely consistent for boys and girls, and for younger and older children.
marital conflict; sensitization; reactivity
Depression is known to be associated with a wide array of environmental factors. Such associations are due at least in part to genetic influences on both. This issue has been little explored with preadolescent children. Measures of family chaos and parenting style at age 9 and child depressive symptoms at age 12 were completed by 3,258 twin pairs from the Twins Early Development Study and their parents. Quantitative genetic modeling was used to explore common and unique genetic and environmental influences on both family environment and later depressive symptoms. Depressive symptoms at age 12 were significantly heritable. Moderate genetic effects influenced parenting style and family chaos at the age of 9, indicating gene–environment correlation. There were significant genetic correlations between family environment and depressive symptoms. There was some evidence of a Gene×Environment interaction, with stronger genetic effects on depressive symptoms for children with more suboptimal family environment. There was an Environment×Environment interaction, with effects of nonshared environment on depressive symptoms stronger for twins with more adverse parenting experiences. There is some evidence for gene–environment correlation between aspects of family environment in middle childhood and subsequent depressive symptoms. This suggests that one of the mechanisms by which genes lead to depressive symptoms may be by themselves influencing depressogenic environments.
This study examined developmentally-salient risk and protective factors of adolescent substance use assessed during early childhood and early adolescence using a sample of 310 low-income boys. Child problem behavior and proximal family risk and protective factors (i.e., parenting, maternal depression) during early childhood, as well as child and family factors and peer deviant behavior during adolescence were explored as potential precursors to later substance use during adolescence using structural equation modeling. Results revealed that early childhood risk and protective factors (i.e., child externalizing problems, mothers’ depressive symptomatology, and nurturant parenting) were indirectly related to substance use at the age of 17 via risk and protective factors during early and middle adolescence (i.e., parental knowledge and externalizing problems). The implications of these findings for early prevention and intervention are discussed.
substance use; adolescents; early risk factors; longitudinal research
Sterba and Bauer's Keynote Article discusses the blurred distinction between theoretical principles and analytical methods in the person-oriented approach as problematic and review which of the person-oriented principles are testable under the four types of latent variable models for longitudinal data. Although the issue is important, some arbitrariness exists in determining whether a given principle can be tested within each analytic approach. To close the gap between person-oriented theory and methods and to extend the person-oriented approach more generally, it is necessary to embrace both variable-oriented and person-oriented methods because it is not the individual analytic methods but how studies are implemented as a whole that defines the person-oriented approach. Three areas in developmental psychopathology are discussed in which variable-oriented and person-oriented methods can be complementary. The need to better understand the target system using an appropriate person-specific tool is graphically illustrated. Several concepts of dynamic systems such as attractors, phase transitions, and control parameters are illustrated using experimentally perturbed cardiac rhythms (heart rate variability) as an example in the context of translational alcohol research.
We investigated the roles of sex and respiratory sinus arrhythmia (RSA), an index of autonomic parasympathetic nervous system activity, as predictors of codeveloping externalizing and internalizing symptoms in middle childhood. We expected that sex, baseline RSA (RSA-B), and RSA reactivity (RSA-R) to two types of tasks would interact to differentiate co-occurring trajectories of symptoms. We tested these hypotheses by combining longitudinal data from two independent samples (n = 390; 210 girls, 180 boys) with repeated measures at ages 8, 9, 10, and 11. RSA-R was measured in response to a socially stressful and frustrating stressor. Indicators of growth in externalizing and internalizing symptoms were derived from multiple domain growth models and used in person-centered growth mixture analyses. Three groups of externalizing and internalizing trajectories were found. Profile membership was predicted by several two-way interactions among sex, RSA-B, or RSA-R but was not predicted by three-way interactions. Children with low RSA-B and strong RSA withdrawal, girls with low RSA-B, and girls with strong RSA withdrawal were more likely to be on a developmental trajectory of low externalizing symptoms and moderately elevated internalizing symptoms. Membership in the high externalizing and high internalizing trajectory was predicted by weak RSA withdrawal for boys and strong RSA withdrawal for girls. The type of stressor task also played a role in predicting probability of profile membership. Results are discussed in the context of developmental psychobiology and implications for the codevelopment of psychopathology symptoms in childhood.
Many young people who are mistreated by an adult, victimized by bullies, criminally assaulted, or who witness domestic violence react to this violence exposure by developing behavioral, emotional, or learning problems. What is less well known is that adverse experiences like violence exposure can lead to hidden physical alterations inside a child’s body, alterations which may have adverse effects on life-long health. We discuss why this is important for the field of developmental psychopathology and for society, and we recommend that stress-biology research and intervention science join forces to tackle the problem. We examine the evidence base in relation to stress-sensitive measures for the body (inflammatory reactions, telomere erosion, epigenetic methylation, and gene expression) and brain (mental disorders, neuroimaging, and neuropsychological testing). We also review promising interventions for families, couples, and children that have been designed to reduce the effects of childhood violence exposure. We invite intervention scientists and stress-biology researchers to collaborate in adding stress-biology measures to randomized clinical trials of interventions intended to reduce effects of violence exposure and other traumas on young people.
Low socioeconomic status (SES) background has been identified as a risk for several mental disorders. However evidence regarding SES and the developmental course of personality disorder (PD) has not been addressed. Nor is it clear whether an SES relationship to PD symptom course may be attributable to known associated risks. Further, specificity of such relationships to a particular PD diagnostic pattern independent of comorbidity with other PD or with depression has not been investigated. Data are from a general population studied longitudinally between ages 10 and 36 in four assessment waves. Effects of SES-associated risks on the level of symptoms of schizotypal and borderline disorders are estimated and compared to effects on depressive symptoms. Low family SES had robust modest independent effects on both PDs over the entire age span despite substantial cumulative effects of trauma history, stressful recent life events, IQ, poor parenting, and comorbid symptoms. SES effects on depressive symptoms were generally absent, but a small “protective” effect of low SES appeared when comorbidity with PD symptoms was taken into account. Cumulatively, these risks account for developmental failures of substantial magnitude and consequence, marking the importance of understanding the remaining mechanisms of SES effects and programmatic implications for minimizing associated risk.
A randomized clinical trial was conducted to evaluate the efficacy of interpersonal psychotherapy (IPT) for ethnically and racially diverse, economically disadvantaged women with Major Depressive Disorder (MDD). Non-treatment seeking urban women (N=128; M age=25.40; SD=4.98) with infants were recruited from the community. Participants were at or below the poverty level: 59.4% identified as Black and 21.1% were Hispanic. Women were screened for depressive symptoms using the Center for Epidemiologic Studies-Depression Scale; the Diagnostic Interview Schedule was used to confirm MDD diagnosis. Participants were randomized to individual IPT or Enhanced Community Standard (ECS). Depressive symptoms were assessed before, after, and eight months post treatment with the Beck Depression Inventory-II (BDI-II) and Revised Hamilton Rating Scale for Depression (HRSD-R). The Social Support Behaviors Scale (SBS), Social Adjustment Scale-Self Report (SAS-SR) and Perceived Stress Scale (PSS) were administered to examine mediators of outcome at follow-up. Treatment effects were evaluated with a growth mixture model for randomized trials using Complier-Average Causal Effect (CACE) estimation. Depressive symptoms trajectories from baseline through post-intervention to follow-up showed significant decreases among the IPT group compared to the ECS group. Changes on PSS and SBS mediated sustained treatment outcome.
depression; interpersonal psychotherapy; randomized clinical trial; diverse populations
Substance use is a major contributor to morbidity and mortality among American adolescents. Conduct problems and depressive symptoms have each been associated with adolescent substance use. Although they are highly comorbid, the relation of the interaction of conduct problems and depressive symptoms to substance use in not clear. In a national sample of 8th, 10th, and 12th grade students from Monitoring the Future surveys, latent moderated structural equation modeling was used to estimate the association of conduct problems, depressive symptoms, and their interaction to alcohol, cigarette, and marijuana use. Moderation by age and sex was tested. The interaction of conduct problems with depressive symptoms was a strong predictor of substance use, particularly among younger adolescents. With few exceptions, adolescents with high levels of both conduct problems and depressive symptoms used substances most frequently. Conduct problems were a strong predictor of substance use, with larger effects in males; depressive symptoms were a weak predictor, with larger effects in females. Whereas conduct problems are often thought to be a primary predictor of substance use, this study revealed that depressive symptoms potentiate the relation of conduct problems to substance use. Therefore, substance use prevention efforts should target both depressive symptoms and conduct problems.
Depressive symptoms; conduct problems; adolescence; substance use
Research has shown a developmental process of “maturing out” of alcohol involvement beginning in young adulthood, but the precise nature of changes characterizing maturing out is unclear. We used latent transition analysis to investigate these changes in a high-risk sample from a longitudinal study of familial alcoholism (N=844; 51% children of alcoholics; 53% male, 71% non-Hispanic Caucasian, 27% Hispanic). Analyses classified participants into latent drinking statuses during late adolescence (ages 17–22), young adulthood (ages 23–28), and adulthood (ages 29–40), and characterized transitions among these statuses over time. The resulting four statuses were abstainers, low-risk drinkers who typically drank less than weekly and rarely binged or showed drinking problems, moderate-risk drinkers who typically binged less than weekly and showed moderate risk for drinking problems, and high-risk drinkers who typically binged at least weekly and showed high risk for drinking problems. Maturing out between late adolescence and young adulthood was most common among initial high-risk drinkers, but they typically declined to moderate-risk drinking rather than to non-risky drinking statuses. This suggests that the developmental phenomenon of maturing out pertains primarily to relatively high-risk initial drinkers, and that many high-risk drinkers who “mature out” merely reduce rather than eliminate their risky drinking.
Maturing out; drinking; familial alcoholism
Is it always or necessarily the case that common and important parenting practices are better insofar as they occur more often, or worse because they occur less often? Perhaps, less is more, or some is more. To address this question, we studied mothers’ microcoded contingent responsiveness to their infants (M = 5.4 months, SD = 0.2) in relation to independent global judgments of the same mothers’ parenting sensitivity. In a community sample of 335 European American dyads, videorecorded infant and maternal behaviors were timed microanalytically throughout an extended home observation; separately and independently, global maternal sensitivity was rated macroanalytically. Sequential analysis and spline regression showed that, as maternal contingent responsiveness increased, judged maternal sensitivity increased to significance on the contingency continuum, after which mothers who were even more contingent were judged less sensitive. Just significant levels of maternal responsiveness are deemed optimally sensitive. Implications of these findings for typical and atypical parenting, child development, and intervention science are discussed.
This article serves to outline a research paradigm to investigate main effects and interactions of genes, environment, and development on behavior and psychiatric illness. We provide a historical context for candidate gene studies and genome-wide association studies, including benefits, limitations, and expected payoff. Using substance use and abuse as our driving example, we then turn to the importance of etiological psychological theory in guiding genetic, environmental, and developmental research, as well as the utility of refined phenotypic measures, such as endophenotypes, in the pursuit of etiological understanding and focused tests of genetic and environmental associations. Phenotypic measurement has received considerable attention and is informed by psychometrics, while the environment remains relatively poorly measured and is often confounded with genetic effects (i.e., gene-environment correlation). Genetically-informed designs which—thanks to ever cheaper genotyping—are no longer are limited to twin and adoption studies, are required to understand environmental influences. Finally, we outline the vast amount of individual differences in structural genomic variation, most of which remains to be leveraged in genetic association tests. While the genetic data can be burdensomely massive (tens of millions of variants per person), we argue that improved understanding of genomic structure and function will provide investigators with new tools to test specific a priori hypotheses derived from etiological psychological theory, much like current candidate gene research, but with less confusion and more payoff than candidate gene research has to date.
The study of gene expression (i.e., the study of the transcriptome) in different cells and tissues allows us to understand the molecular mechanisms of their differentiation, development and functioning. In this article, we describe some studies of gene-expression profiling for the purposes of understanding developmental (age-related) changes in the brain using different technologies (e.g., DNA-Microarray) and the new and increasingly popular RNA-Seq. We focus on advancements in studies of gene expression in the human brain, which have provided data on the structure and age-related variability of the transcriptome in the brain. We present data on RNA-Seq of the transcriptome in three distinct areas of the neocortex from different ages: mature and elderly individuals. We report that most age-related transcriptional changes affect cellular signaling systems, and, as a result, the transmission of nerve impulses. In general, the results demonstrate the high potential of RNA-Seq for the study of distinctive features of gene expression among cortical areas and the changes in expression through normal and atypical development of the central nervous system.
Based on numerous suggestions in the literature, we evaluated lexical decision (LD) as a putative endophenotype for reading comprehension by investigating heritability estimates and segregation analyses parameter estimates for both of these phenotypes. Specifically, in a segregation analysis of a large sample of families, we established that there is little to no overlap between genes contributing to LD and reading comprehension and that the genetic mechanism behind LD derived from this analysis appears to be more complex than that for reading comprehension. We conclude that in our sample, LD is not a good candidate as an endophenotype for reading comprehension, despite previous suggestions from the literature. Based on this conclusion, we discuss the role and benefit of the endophenotype approach in studies of complex human cognitive functions.
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.