The present study examined the intergenerational transmission of internalizing and externalizing symptom severity, which indexes comorbidity, and symptom directionality, which indicates differentiation toward externalizing versus internalizing problems. Data are from 854 male and female, same-sex adult twin pairs born between 1926 and 1971 (32–60 years old, M = 44.9 years, SD = 4.9 years) from the Twin and Offspring Study in Sweden and their adolescent offspring (11–22 years old, M = 15.7 years, SD = 2.4 years, 52% female). Children-of-twins models revealed additive (9%) and dominant (45%) genetic and nonshared environmental (47%) influences on twins’ symptom severity, and additive genetic (39%) and nonshared environmental (61%) influences on twins’ symptom directionality. Both comorbid problems and preponderance of symptoms of a particular – internalizing versus externalizing – spectrum were correlated across parent and child generations, although associations were modest especially for directionality (i.e., transmission of specific symptom type). By interpreting findings alongside a recent study of adolescent twins, we demonstrate that the intergenerational transmission of symptom severity and symptom directionality are both unlikely to be attributable to genetic transmission, are both likely to be influenced by direct phenotypic transmission and/or nonpassive rGE, and the intergenerational transmission of symptom severity is also likely to be influenced by passive rGE.

This research examines maternal smoking during pregnancy and risk for poorer executive function in siblings discordant for exposure. Data (N = 173 families) were drawn from the Missouri Mothers and Their Children study, a sample, identified using birth records (years 1998–2005), in which mothers changed smoking behavior between two pregnancies (Child 1 [older sibling]: Mage = 12.99; Child 2 [younger sibling]: Mage = 10.19). A sibling comparison approach was used, providing a robust test for the association between maternal smoking during pregnancy and different aspects of executive function in early-mid adolescence. Results suggested within-family (i.e., potentially causal) associations between maternal smoking during pregnancy and one working memory task (visual working memory) and one response inhibition task (color-word interference), with increased exposure associated with decreased performance. Maternal smoking during pregnancy was not associated with stop-signal reaction time, cognitive flexibility/set-shifting, or auditory working memory. Initial within-family associations between maternal smoking during pregnancy and visual working memory as well as color-word interference were fully attenuated in a model including child and familial covariates. These findings indicate that exposure to maternal smoking during pregnancy may be associated with poorer performance on some, but not all skills assessed; however, familial transmission of risk for low executive function appears more important.

Theoretical models of attention-deficit/hyperactivity disorder implicate neurocognitive dysfunction, yet neurocognitive functioning covers a range of abilities that may not all be linked with inattention. This study (a) investigated the single nucleotide polymorphism (SNP) heritability (h2SNP) of inattention and aspects of neurocognitive efficiency (memory, social cognition, executive function, and complex cognition) based on additive genome-wide effects; (b) examined if there were shared genetic effects among inattention and each aspect of neurocognitive efficiency; and (c) conducted an exploratory genome-wide association study to identify genetic regions associated with inattention. The sample included 3,563 participants of the Philadelphia Neurodevelopmental Cohort, a general population sample aged 8–21 years who completed the Penn Neurocognitive Battery. Data on inattention was obtained with the Kiddie Schedule of Affective Disorders (adapted). Genomic relatedness matrix restricted maximum likelihood was implemented in genome-wide complex trait analysis. Analyses revealed significant h2SNP for inattention (20%, SE = 0.08), social cognition (13%, SE = 0.08), memory (17%, SE = 0.08), executive function (25%, SE = 0.08), and complex cognition (24%, SE = 0.08). There was a positive genetic correlation (0.67, SE = 0.37) and a negative residual covariance (−0.23, SE = 0.06) between inattention and social cognition. No SNPs reached genome-wide significance for inattention. Results suggest specificity in genetic overlap among inattention and different aspects of neurocognitive efficiency.

Children exposed to maternal smoking during pregnancy (MSDP) exhibit difficulties in executive function (EF) from infancy through adolescence. Due to the developmental significance of EF as a predictor of adaptive functioning throughout the life span, the MSDP–EF relation has clear public health implications. In this paper, we provide a comprehensive review of the literature on the relationship between MSDP and offspring EF across development; consider brain-based assessments, animal models, and genetically informed studies in an effort to elucidate plausible pathways of effects; discuss implications for prevention and intervention; and make calls to action for future research.

The Missouri Mothers and Their Children Study (MO-MATCH) was specifically designed to critically investigate prenatal environmental influences on child attention problems and associated learning and cognitive deficits. The project began as a pilot study in 2004 and was formally launched in 2008. Participants in the study were initially identified via the Department of Vital Statistics birth record (BR) database. Interview and lab-based data were obtained from: (1) mothers of Missouri-born children (born 1998–2005), who smoked during one pregnancy but not during another pregnancy; (2) biological fathers when available; and (3) the children (i.e., full sibling pairs discordant for exposure to maternal smoking during pregnancy (SDP). This within-mother, between-pregnancy contrast provides the best possible methodological control for many stable maternal and familial confounding factors (e.g., heritable and socio-demographic characteristics of the mother that predict increased probability of SDP). It also controls for differences between mothers who do and do not smoke during pregnancy, and their partners, that might otherwise artifactually create, or alternatively mask, associations between SDP and child outcomes. Such a design will therefore provide opportunities to determine less biased effect sizes while also allowing us to investigate (on a preliminary basis) the possible contribution of paternal or other second-hand smoke exposure during the pre, peri, and postnatal periods to offspring outcome. This protocol has developed a cohort that can be followed longitudinally through periods typically associated with increased externalizing symptoms and substance used initiation.

Information-processing biases may contribute to the intergenerational transmission of depression. There is growing evidence that children of depressed mothers exhibit attentional biases for sad faces. However, findings are mixed as to whether this bias reflects preferential attention toward, versus attentional avoidance of, sad faces, suggesting the presence of unmeasured moderators. To address these mixed findings, we focused on the potential moderating role of genes associated with hypothalamic–pituitary–adrenal axis reactivity. Participants included children (8–14 years old) of mothers with (n = 81) and without (n = 81) a history of depression. Eye movements were recorded while children passively viewed arrays of angry, happy, sad, and neutral faces. DNA was obtained from buccal cells. Children of depressed mothers exhibited more sustained attention to sad faces than did children of nondepressed mothers. However, it is important that this relation was moderated by children's genotype. Specifically, children of depressed mothers who carried reactive genotypes across the corticotropin-releasing hormone type 1 receptor (CHRH1) TAT haplotype and FK506 binding protein 5 (FKBP5) rs1360780 (but not the solute carrier family C6 member 4 [SLC6A4] of the serotonin transporter linked polymorphic region [5-HTTLPR]) exhibited less sustained attention to sad faces and more sustained attention to happy faces. These findings highlight the role played by specific genetic influences and suggest that previous mixed findings may have been due to genetic heterogeneity across the samples.

We examined how genotype–environment correlation processes differ as a function of adolescent age. We tested whether adolescent age moderates genetic and environmental influences on positivity and negativity in mother–adolescent and father–adolescent relationships using parallel samples of twin parents from the Twin and Offspring Study in Sweden and twin/sibling adolescents from the Nonshared Environment in Adolescent Development Study. We inferred differences in the role of passive and nonpassive genotype–environment correlation based on biometric moderation findings. The findings indicated that nonpassive gene–environment correlation played a stronger role for positivity in mother– and father–adolescent relationships in families with older adolescents than in families with younger adolescents, and that passive gene–environment correlation played a stronger role for positivity in the mother–adolescent relationship in families with younger adolescents than in families with older adolescents. Implications of these findings for the timing and targeting of interventions on family relationships are discussed.

The period of in utero development is one of the most critical windows during which adverse intrauterine conditions and exposures can influence the growth and development of the fetus as well as the child's 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 health and behavior remain to be elucidated. This article seeks to explore many of the previously described epigenetic alterations associated with maternal cigarette smoking during pregnancy and assess 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.

This study provides findings to assist in identifying factors that contribute to the current clinical and public health debate of the obesity epidemic. The study examined the genetics of adult-onset weight change in middle-aged male—male twins controlling for weight in early adulthood, lifetime history of tobacco use and alcohol dependence, and aimed to estimate the proportion of genetic factors that influence weight change between early adulthood and middle age in white middle-class males. The study was a classic longitudinal twin design and used Body Mass Index (BMI) for three waves of data collection from the Vietnam Era Twin Registry — induction physicals (∼ 1968), 1987 and 1990 — or periods corresponding between young adulthood and middle age. Univariate heritability estimates for BMI at all three data periods were conducted as well as a Cholesky longitudinal genetic analysis for weight change controlling for BMI at military induction, smoking and alcohol use. Frequency data indicated that the sample was on average classified as normal BMI in their 20s; but BMI gradually increased during the next twenty years. Univariate data for each data period indicated that additive genetic factors accounted for between 63% and 69% of total variance in BMI. The Cholesky longitudinal genetic analysis of BMI87 and BMI90, controlling for BMI at military induction, indicated that more than half of the change in BMI from early adulthood to middle age remains heritable. No shared environmental factors were identified, thus the remainder of the variance was accounted for by nonshared, or unique, environmental factors and error. The data analysis suggests that treatments and public health interventions need to recognize the magnitude of genetic factors if short-term and long-term interventions are to be effective.

The etiology of the observed relationship between reading and mathematics performance was examined by analyzing data from samples of same-sex twin pairs tested in the Colorado Learning Disabilities Research Center. Bivariate phenotypic and genetic structural equation models were fitted to data from 526 twin pairs selected for reading deficits (290 identical and 236 same-sex fraternal) and 355 control pairs (220 identical and 135 same-sex fraternal). Subtests of the Peabody Individual Achievement Test (PIAT; Reading Recognition, Reading Comprehension, and Spelling) were used as measures of reading performance, and scores from the Wechsler Intelligence Scale for Children-Revised (WISC-R) or Wechsler Adult Intelligence Scale-Revised (WAIS-R) Arithmetic subtest, the Wide Range Achievement Test Arithmetic subtest, and the PIAT Math subtest were used as indices for mathematics performance. The results of these confirmatory factor analyses indicate that genetic and environmental covariances between reading and math latent factors do not differ significantly for twin pairs in the proband and control groups. Estimates of heritability for reading performance in the proband and control samples were 0.81 and 0.69, respectively, and those for math performance were 0.88 and 0.67, respectively. Moreover, genetic influences accounted for 83% of the covariation between the reading and math factors in the proband group and for 58% of the covariation between these two latent variables in the control group; in contrast, shared environmental influences did not contribute significantly to the relationship between the reading and math latent factors nor to their independent variation.

Parents of 323 twin pairs with reading disability (RD) reported significantly more problems learning to read (16% of mothers and 33% of fathers) than parents of 309 twin pairs without reading difficulties (6% of mothers and 9% of fathers). These rates of self-reported reading problems in parents of twins are highly similar to those previously obtained in parents of non-twin children with RD and controls, suggesting that the etiology of reading deficits in twin and non-twin children may also be highly similar. Moreover, within both the RD and control samples, twins whose parents self-reported a positive history of reading problems had lower reading performance test scores, on average, than those whose parents reported no reading problems. Therefore, results of the present twin study support those of previous studies with non-twin children in which parental self-reports have been found to provide a valid index of family history status for reading difficulties. Twin Research (2000) 3, 88–91.

Retrospective assessment of maternal smoking or substance use during pregnancy is sometimes unavoidable. The unusually close relationship of twin sister pairs permits comparison of self-report data versus co-twin informant data on substance use during pregnancy. Information about smoking during pregnancy has been gathered from a series of mothers from an Australian volunteer twin panel (576 women reporting on 995 pregnancies), supplemented in many cases by independent ratings of their smoking by twin sister informants (821 pregnancies). Estimates of the proportion of women who had never smoked regularly (56–58%), who had smoked but did not smoke during a particular pregnancy (16–21%), or who smoked throughout the pregnancy (16–18%), were in good agreement whether based on selfreport or twin sister informant data. However, informants underreported cases who smoked during the first trimester but then quit (1–3% versus 7–9% by self-report). Women who smoked throughout pregnancy (by informant report) rarely denied a history of regular smoking (< 1%), although a small proportion of apparent false negative cases were identified where they either denied smoking during a pregnancy (9%) or denied smoking beyond the first trimester (10%). We conclude that retrospective smoking data can safely be used to identify potential associations of later child outcomes with maternal smoking during pregnancy.

Objective: A recent Children-of-Female-Twin design suggests that the association between maternal alcohol use disorder and offspring ADHD is due to a combination of genetic and environmental factors, such as prenatal nicotine exposure. We present here a complementary analysis using a Children-of-Male-Twin design examining the association between paternal alcoholism and offspring attention deficit hyperactivity problems (ADHP). Methods: Children-of-twins design: offspring were classified into 4 groups of varying genetic and environmental risk based on father and co-twin's alcohol dependence status. Results: Univariate results are suggestive of a genetic association between paternal alcohol dependence and broadly defined offspring ADHP. Specifically, offspring of male twins with a history of DSM-III-R alcohol dependence, as well as offspring of non-alcohol dependent monozygotic twins whose co-twin was alcohol dependent, were significantly more likely to exhibit ADHP than control offspring. However, multivariate models show maternal variables independently predicting increased risk for offspring ADHP and significantly decreased support for a genetic mechanism of parent-to-child transmission. Conclusions: In support of earlier work, maternal variables (i.e., maternal ADHD and prenatal exposure) were strongly associated with child ADHP; however, the role of paternal alcohol dependence influences was not definitive. While genetic transmission may be important, the association between paternal alcohol dependence and child ADHP is more likely to be indirect and a result of several pathways.

Alcohol abuse and dependence are among the most common psychiatric conditions identified in epidemiological surveys of the general population. The aim of this article is to examine the psychometric properties of Diagnostic and Statistical Manual of Mental Disorders, (4th ed.; DSM-IV; American Psychiatric Association, 1994) criteria for alcohol abuse and dependence using latent class analysis (LCA). Six thousand two hundred and sixty-five young Australian twins (median age 30 years) were interviewed by telephone between 1996 and 2000 using a modified version of the Semi-Structured Assessment for the Genetics of Alcoholism (SSAGA). DSM-IV symptoms of alcohol abuse and dependence were collected by structured diagnostic interview and analyzed using methods of LCA. LCA revealed a 4-class solution for women that classified individuals according to the severity of their alcohol- related problems: no/few problems (66.5%), heavy drinking (23.9%), moderate dependence (7.6%) and severe dependence (2.0%). Among men the preferred solution included 5 classes corresponding to no/few problems (46.4%), heavy drinking (34.3%), moderate dependence (12.2%), severe dependence (3.0%) and abuse (4.0%). Evidence of a male-specific class of alcohol-related problems corresponding to abuse partially supports the DSM conceptualization of alcohol use disorders but suggests that this conceptualization — and measurement — may need to be refined for women. Identification of a male- specific abuse class also has important implications for interventions and treatment as these individuals experienced significant alcohol-related problems and comprised approximately 21% of all men classified with an alcohol use disorder.

Background. Children of alcoholics are significantly more likely to experience high-risk environmental exposures, including prenatal substance exposure, and are more likely to exhibit externalizing problems [e.g. attention deficit hyperactivity disorder (ADHD)]. While there is evidence that genetic influences and prenatal nicotine and/or alcohol exposure play separate roles in determining risk of ADHD, little has been done on determining the joint roles that genetic risk associated with maternal alcohol use disorder (AUD) and prenatal risk factors play in determining risk of ADHD.

Method. Using a children-of-twins design, diagnostic telephone interview data from high-risk families (female monozygotic and dizygotic twins concordant or discordant for AUD as parents) and control families targeted from a large Australian twin cohort were analyzed using logistic regression models.

Results. Offspring of twins with a history of AUD, as well as offspring of non-AUD monozygotic twins whose co-twin had AUD, were significantly more likely to exhibit ADHD than offspring of controls. This pattern is consistent with a genetic explanation for the association between maternal AUD and increased offspring risk of ADHD. Adjustment for prenatal smoking, which remained significantly predictive, did not remove the significant genetic association between maternal AUD and offspring ADHD.

Conclusions. While maternal smoking during pregnancy probably contributes to the association between maternal AUD and offspring ADHD risk, the evidence for a significant genetic correlation suggests: (i) pleiotropic genetic effects, with some genes that influence risk of AUD also influencing vulnerability to ADHD; or (ii) ADHD is a direct risk-factor for AUD.

Background. Genetic influences have been shown to play a major role in determining the risk of attention-deficit hyperactivity disorder (ADHD). In addition, prenatal exposure to nicotine and/or alcohol has also been suggested to increase risk of the disorder. Little attention, however, has been directed to investigating the roles of genetic transmission and prenatal exposure simultaneously.

Method. Diagnostic telephone interview data from parents of Missouri adolescent female twin pairs born during 1975–1985 were analyzed. Logistic regression models were fitted to interview data from a total of 1936 twin pairs (1091 MZ and 845 DZ pairs) to determine the relative contributions of parental smoking and drinking behavior (both during and outside of pregnancy) as risk factors for DSM-IV ADHD. Structural equation models were fitted to determine the extent of residual genetic and environmental influences on ADHD risk while controlling for effects of prenatal and parental predictors on risk.

Results. ADHD was more likely to be diagnosed in girls whose mothers or fathers were alcohol dependent, whose mothers reported heavy alcohol use during pregnancy, and in those with low birth weight. Controlling for other risk factors, risk was not significantly increased in those whose mothers smoked during pregnancy. After allowing for effects of prenatal and childhood predictors, 86% of the residual variance in ADHD risk was attributable to genetic effects and 14% to non-shared environmental influences.

Conclusions. Prenatal and parental risk factors may not be important mediators of influences on risk with much of the association between these variables and ADHD appearing to be indirect.

Background. Genetic influences have been shown to play a major role in determining the risk of alcohol dependence (AD) in both women and men; however, little attention has been directed to identifying the major sources of genetic variation in AD risk.

Method. Diagnostic telephone interview data from young adult Australian twin pairs born between 1964 and 1971 were analyzed. Cox regression models were fitted to interview data from a total of 2708 complete twin pairs (690 MZ female, 485 MZ male, 500 DZ female, 384 DZ male, and 649 DZ female/male pairs). Structural equation models were fitted to determine the extent of residual genetic and environmental influences on AD risk while controlling for effects of sociodemographic and psychiatric predictors on risk.

Results. Risk of AD was increased in males, in Roman Catholics, in those reporting a history of major depression, social anxiety problems, and conduct disorder, or (in females only) a history of suicide attempt and childhood sexual abuse; but was decreased in those reporting Baptist, Methodist, or Orthodox religion, in those who reported weekly church attendance, and in university-educated males. After allowing for the effects of sociodemographic and psychiatric predictors, 47% (95% CI 28–55) of the residual variance in alcoholism risk was attributable to additive genetic effects, 0% (95% CI 0–14) to shared environmental factors, and 53% (95% CI 45–63) to non-shared environmental influences.

Conclusions. Controlling for other risk factors, substantial residual heritability of AD was observed, suggesting that psychiatric and other risk factors play a minor role in the inheritance of AD.