The multifactorial nature of psychopathology, whereby both genetic and environmental factors contribute risk, has long been established. In this paper, we provide an update on genetically informative designs that are utilized to disentangle genetic and environmental contributions to psychopathology. We provide a brief reminder of quantitative behavioral genetic research designs that have been used to identify potentially causal environmental processes, accounting for genetic contributions. We also provide an overview of recent molecular genetic approaches that utilize genome-wide association study data which are increasingly being applied to questions relevant to psychopathology research. While genetically informative designs typically have been applied to investigate the origins of psychopathology, we highlight how these approaches can also be used to elucidate potential causal environmental processes that contribute to developmental course and outcomes. We highlight the need to use genetically sensitive designs that align with intervention and prevention science efforts, by considering strengths-based environments to investigate how positive environments can mitigate risk and promote children’s strengths.

An enduring issue in the study of mental health is identifying developmental processes that explain how childhood characteristics progress to maladaptive forms. We examine the role that behavioral inhibition (BI) has on social anxiety (SA) during adolescence in 868 families of twins assessed at ages 8, 13, and 15 years. Multimodal assessments of BI and SA were completed at each phase, with additional measures (e.g., parenting stress) for parents and twins. Analyses were conducted in several steps: first, we used a cross-lagged panel model to demonstrate bidirectional paths between BI and SA; second a biometric Cholesky decomposition showed that both genetic and environmental influences on childhood BI also affect adolescent SA; next, multilevel phenotypic models tested moderation effects between BI and SA. We tested seven potential moderators of the BI to SA prediction in individual models and included only those that emerged as significant in a final conditional model examining predictors of SA. Though several main effects emerged as significant, only parenting stress had a significant interaction with BI to predict SA, highlighting the importance of environmental moderators in models examining temperamental effects on later psychological symptoms. This comprehensive assessment continues to build the prototype for such developmental psychopathology models.

Children with callous–unemotional (CU) traits are at risk for severe conduct problems. While CU traits are moderately heritable, parenting also predicts risk. However, few studies have investigated whether parenting factors (e.g., acceptance, conflict, parental psychopathology) moderate the etiology of CU traits, while accounting for gene–environment correlations. To address this knowledge gap, we used data from 772 twin pairs from the Adolescent Brain and Cognitive Development Study to test bivariate models that explored overlapping etiological influences on CU traits and child reports of their parenting environment. We also used gene-by-environment interaction models to test whether parenting moderated genetic versus environmental influences. There were no overlapping etiological influences on CU traits and parental acceptance, but modest genetic and non-shared environmental overlap between CU traits and family conflict. Parental acceptance and psychopathology moderated non-shared environmental influences, with stronger non-shared environmental influences on CU traits among children who experienced lower parental acceptance and greater parental psychopathology. Family conflict only moderated environmental influences when models did not covary for conduct problems. Parental acceptance and parental psychopathology may be specific environmental protective and risk factors for CU traits, whereas family conflict may represent a general environmental risk factor for both CU traits and conduct problems.

The present study examined putative environmental predictors of adolescent substance use, using a prospective adoption design to distinguish between environmental mediation (i.e., parenting influencing adolescent substance use), passive gene–environment correlation (i.e., parental genetic predisposition influencing the association between parenting characteristics and adolescent substance use), and evocative gene–environment correlation (i.e., children’s genetic predisposition influencing parenting). Longitudinal data from the Colorado Adoption Project (395 adoptees, 491 nonadoptees, 485 adoptive parents, and 490 biological parents) were examined. Children (48% girls) were assessed at ages 1 to 17 years. Over 90% of the sample were non-Hispanic White. Associations between parenting and adolescent substance use were compared between adoptive and nonadoptive families. Positive, negative, and inconsistent parenting measures in early childhood through adolescence were not consistently associated with adolescent substance use, with only 6% of correlations being statistically significant (r = −0.152 to .207). However, parent–child relationship quality assessed from childhood to adolescence and orientation to parents assessed during adolescence were significantly, negatively associated with adolescent substance use, with 71% of correlations being statistically significant (r = −0.88 to −0.11). There was little evidence of sex differences in the associations. Environmental mediation, rather than passive or evocative gene–environment correlation, explained most associations.

Some children are more affected by specific family environments than others, as a function of differences in their genetic make-up. However, longitudinal studies of genetic moderation of parenting effects during early childhood have not been conducted. We examined developmental profiles of child behavior problems between 18 months and age 8 in a longitudinal parent–offspring sample of 361 adopted children. In toddlerhood (18 months), observed structured parenting indexed parental guidance in service of task goals. Biological parent psychopathology served as an index of genetic influences on children’s behavior problems. Four profiles of child behavior problems were identified: low stable (11%), average stable (50%), higher stable (29%), and high increasing (11%). A multinominal logistic regression analysis indicated a genetically moderated effect of structured parenting, such that for children whose biological mother had higher psychopathology, the odds of the child being in the low stable group increased as structured parenting increased. Conversely, for children whose biological mother had lower psychopathology, the odds of being in the low stable group was reduced when structured parenting increased. Results suggest that increasing structured parenting is an effective strategy for children at higher genetic risk for psychopathology, but may be detrimental for those at lower genetic risk.

Deficits in executive functioning both run in families and serve as a transdiagnostic risk factor for psychopathology. The present study employed twin modeling to examine parenting as an environmental pathway underlying the intergenerational transmission of executive functioning in an at-risk community sample of children and adolescents (N = 354 pairs, 167 monozygotic). Using structural equation modeling of multi-informant reports of parenting and a multi-method measure of child executive functioning, we found that better parent executive functioning related to less harsh, warmer parenting, which in turn related to better child executive functioning. Second, we assessed the etiology of executive functioning via the nuclear twin family model, finding large non-shared environmental effects (E = .69) and low-to-moderate heritability (A = .22). We did not find evidence of shared environmental effects or passive genotype–environment correlation. Third, a bivariate twin model revealed significant shared environmental overlap between both warm and harsh parenting and child executive functioning (which may indicate either passive genotype–environment correlation or environmental mediation), and non-shared environmental overlap between only harsh parenting and child executive functioning (indicating an effect of harsh parenting separable from genetic confounds). In summary, genetics contribute to the intergenerational transmission of executive functioning, with environmental mechanisms, including harsh parenting, also making unique contributions.

Twin studies demonstrate significant environmental influences and a lack of genetic effects on disordered eating before puberty in girls. However, genetic factors could act indirectly through passive gene–environment correlations (rGE; correlations between parents’ genes and an environment shaped by those genes) that inflate environmental (but not genetic) estimates. The only study to explore passive rGE did not find significant effects, but the full range of parental phenotypes (e.g., internalizing symptoms) that could impact daughters’ disordered eating was not examined. We addressed this gap by exploring whether parents’ internalizing symptoms (e.g., anxiety, depressive symptoms) contribute to daughters’ eating pathology through passive rGE. Participants were female twin pairs (aged 8–14 years; M = 10.44) in pre-early puberty and their biological parents (n = 279 families) from the Michigan State University Twin Registry. Nuclear twin family models explored passive rGE for parents’ internalizing traits/symptoms and twins’ overall eating disorder symptoms. No evidence for passive rGE was found. Instead, environmental factors that create similarities between co-twins (but not with their parents) and unique environmental factors were important. In pre-early puberty, genetic factors do not influence daughters’ disordered eating, even indirectly through passive rGE. Future research should explore sibling-specific and unique environmental factors during this critical developmental period.

Although it is well known that parental depression is transmitted within families across generations, the etiology of this transmission remains unclear. Our goal was to develop a novel study design capable of explicitly examining the etiologic sources of intergenerational transmission. We specifically leveraged naturally-occurring variations in genetic relatedness between parents and their adolescent children in the 720 families participating in the Nonshared Environment in Adolescent Development (NEAD) study, 58.5% of which included a rearing stepparent (nearly always a stepfather). Results pointed squarely to the environmental transmission of psychopathology between fathers and children. Paternal depression was associated with adolescent depression and adolescent behavior problems (i.e., antisocial behavior, headstrong behavior, and attention problems) regardless of whether or not fathers and their children were genetically related. Moreover, these associations persisted to a subset of “blended” families in which the father was biologically related to one participating child but not to the other, and appeared to be mediated via father–child conflict. Such findings are not only fully consistent with the environmental transmission of psychopathology across generations, but also add to extant evidence that parent–child conflict is a robust and at least partially environmental predictor of adolescent psychopathology.

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.

Sports participation, physical activity, and friendship quality are theorized to have protective effects on the developmental emergence of substance use and self-harm behavior in adolescence, but existing research has been mixed. This ambiguity could reflect, in part, the potential for confounding of observed associations by genetic and environmental factors, which previous research has been unable to rigorously rule out. We used data from the prospective, population-based Child and Adolescent Twin Study in Sweden (n = 18,234 born 1994–2001) and applied a co-twin control design to account for potential genetic and environmental confounding of sports participation, physical activity, and friendship quality (assessed at age 15) as presumed protective factors for adolescent substance use and self-harm behavior (assessed at age 18). While confidence intervals widened to include the null in numerous co-twin control analyses adjusting for childhood psychopathology, parent-reported sports participation and twin-reported positive friendship quality were associated with increased odds of alcohol problems and nicotine use. However, parent-reported sports participation, twin-reported physical activity, and twin-reported friendship quality were associated with decreased odds of self-harm behavior. The findings provide a more nuanced understanding of the risks and benefits of putative protective factors for risky behaviors that emerge during adolescence.

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.

The DNA revolution has energized research on interactions between genes and environments (GxE) by creating indices of G (polygenic scores) that are powerful predictors of behavioral traits. Here, we test the extent to which polygenic scores for attention-deficit/hyperactivity disorder and neuroticism moderate associations between parent reports of their children’s environmental risk (E) at ages 3 and 4 and teacher ratings of behavior problems (hyperactivity/inattention, conduct problems, emotional symptoms, and peer relationship problems) at ages 7, 9 and 12. The sampling frame included up to 6687 twins from the Twins Early Development Study. Our analyses focused on relative effect sizes of G, E and GxE in predicting behavior problems. G, E and GxE predicted up to 2%, 2% and 0.4%, respectively, of the variance in externalizing behavior problems (hyperactivity/inattention and conduct problems) across ages 7, 9 and 12, with no clear developmental trends. G and E predictions of emotional symptoms and peer relationship problems were weaker. A quarter (12 of 48) of our tests of GxE were nominally significant (p = .05). Increasing the predictive power of G and E would enhance the search for GxE.

This study examined the independent and interactive effects of genetic risk for alcohol use disorder (AUD), parenting behaviors, and family environment on childhood impulsivity. Data were drawn from White (n = 5,991), Black/African American (n = 1,693), and Hispanic/Latino (n = 2,118) youth who completed the baseline assessment (age 9–10) and had genotypic data available from the Adolescent Brain Cognitive Development Study. Participants completed questionnaires and provided saliva or blood samples for genotyping. Results indicated no significant main effects of AUD genome-wide polygenic scores (AUD-PRS) on childhood impulsivity as measured by the UPPS-P scale across racial/ethnic groups. In general, parental monitoring and parental acceptance were associated with lower impulsivity; family conflict was associated with higher impulsivity. There was an interaction effect between AUD-PRS and family conflict, such that family conflict exacerbated the association between AUD-PRS and positive urgency, only among Black/African American youth. This was the only significant interaction effect detected from a total of 45 tests (five impulsivity dimensions, three subsamples, and three family factors), and thus may be a false positive and needs to be replicated. These findings highlight the important role of parenting behaviors and family conflict in relation to impulsivity among children.

Genetic factors contribute to the intergenerational transmission of alcohol misuse, but not all individuals at high genetic risk develop problems. The present study examined adolescent relationships with parents, peers, and romantic partners as predictors of realized resistance, defined as high biological risk for disorder combined with a healthy outcome, to alcohol initiation, heavy episodic drinking, and alcohol use disorder (AUD). Data were from the Collaborative Study on the Genetics of Alcoholism (N = 1,858; 49.9% female; mean age at baseline = 13.91 years). Genetic risk, indexed using family history density and polygenic risk scores for alcohol problems and AUD, was used to define alcohol resistance. Adolescent predictors included parent-child relationship quality, parental monitoring, peer drinking, romantic partner drinking, and social competence. There was little support for the hypothesis that social relationship factors would promote alcohol resistance, with the exception that higher father-child relationship quality was associated with higher resistance to alcohol initiation ( $$\hat \beta $$ = −0.19, 95% CI = −0.35, −0.03). Unexpectedly, social competence was associated with lower resistance to heavy episodic drinking ( $$\hat \beta $$ = 0.10, 95% CI = 0.01, 0.20). This pattern of largely null effects underscores how little is known about resistance processes among those at high genetic risk for AUD.

Alcohol use and dependence are strongly affected by variation in aldehyde dehydrogenase (ALDH2) and, to a lesser extent, alcohol dehydrogenase (ADH1B) genes. We use this genetic variation with an adoption design to test the causal role of alcohol use on other drug use, as well as the moderating role of adoptive parent, sibling, and peer alcohol use. Longitudinal models were run on 412 genotyped adopted individuals of East Asian ancestry with multiple assessments between ages 14 and 40. We found robust associations between alcohol frequency, quantity, and maximum drinks and ALDH2, but not ADH1B, status. The magnitude of the ALDH2 protective effect increased with age, particularly for maximum drinks, though estimates were smaller than previously reported in ancestrally similar individuals in East/North-East Asian countries. These results suggest that sociocultural factors in Minnesota may reduce the protective effects of ALDH2. We found that peer alcohol use, but not parent or sibling use, predicted adopted offspring’s use, and that these environmental influences did not vary by ALDH2 status. Finally, we did not find strong evidence of associations between ALDH2 status and tobacco, marijuana, or illegal drug use, contrary to expectation if alcohol serves as a gateway to use of other drugs.

The purpose of this study was to examine possible pathways by which genetic risk associated with externalizing is transmitted in families. We used molecular data to disentangle the genetic and environmental pathways contributing to adolescent externalizing behavior in a sample of 1,111 adolescents (50% female; 719 European and 392 African ancestry) and their parents from the Collaborative Study on the Genetics of Alcoholism. We found evidence for genetic nurture such that parental externalizing polygenic scores were associated with adolescent externalizing behavior, over and above the effect of adolescents’ own externalizing polygenic scores. Mediation analysis indicated that parental externalizing psychopathology partly explained the effect of parental genotype on children’s externalizing behavior. We also found evidence for evocative gene-environment correlation, whereby adolescent externalizing polygenic scores were associated with lower parent–child communication, less parent–child closeness, and lower parental knowledge, controlling for parental genotype. These effects were observed among participants of European ancestry but not African ancestry, likely due to the limited predictive power of polygenic scores across ancestral background. These results demonstrate that in addition to genetic transmission, genes influence offspring behavior through the influence of parental genotypes on their children’s environmental experiences, and the role of children’s genotypes in shaping parent–child relationships.

Parents share half of their genes with their children, but they also share background social factors and actively help shape their child’s environment – making it difficult to disentangle genetic and environmental causes of parent–offspring similarity. While adoption and extended twin family designs have been extremely useful for distinguishing genetic and nongenetic parental influences, these designs entail stringent assumptions about phenotypic similarity between relatives and require samples that are difficult to collect and therefore are typically small and not publicly shared. Here, we describe these traditional designs, as well as modern approaches that use large, publicly available genome-wide data sets to estimate parental effects. We focus in particular on an approach we recently developed, structural equation modeling (SEM)-polygenic score (PGS), that instantiates the logic of modern PGS-based methods within the flexible SEM framework used in traditional designs. Genetically informative designs such as SEM-PGS rely on different and, in some cases, less rigid assumptions than traditional approaches; thus, they allow researchers to capitalize on new data sources and answer questions that could not previously be investigated. We believe that SEM-PGS and similar approaches can lead to improved insight into how nature and nurture combine to create the incredible diversity underlying human behavior.

Context-appropriate infant physiological functioning may support emotion regulation and mother–infant emotion coregulation. Among a sample of 210 low-income Mexican-origin mothers and their 24-week-old infants, dynamic structural equation modeling (DSEM) was used to examine whether within-infant vagal functioning accounted for between-dyad differences in within-dyad second-by-second emotion regulation and coregulation during free play. Vagal functioning was captured by within-infant mean and variability (standard deviation) of respiratory sinus arrhythmia (RSA) during free play. Infant emotion regulation was quantified as emotional equilibria (within-person mean), volatility (within-person deviation from equilibrium), carryover (how quickly equilibrium is restored following a disturbance), and feedback loops (the extent to which prior affect dampens or amplifies subsequent affect) in positive and negative affect during free play; coregulation was quantified as the influence of one partner's affect on the other's subsequent affect. Among infants with lower RSA variability, positive affect fluctuated around a higher equilibrium, and negative affect fluctuated around a lower equilibrium; these infants exhibited feedback loops where their positive affect dampened their subsequent negative affect. As expected, infants with higher mean RSA exhibited more volatility in positive affect, feedback loops between their positive and negative affect, and stronger mother-driven emotion coregulation. The results highlight differences in simultaneously occurring biological and emotion regulation.

While substantial research supports the role of parent–child interactions on the emergence of psychiatric symptoms, few studies have explored biological mechanisms for this association. The current study explored behavioral and neural parent–child synchronization during frustration and play as predictors of internalizing and externalizing behaviors across a span of 1.5 years. Parent–child dyads first came to the laboratory when the child was 4–5 years old and completed the Disruptive Behavior Diagnostic Observation Schedule: Biological Synchrony (DB-DOS: BioSync) task while functional near-infrared spectroscopy (fNIRS) data were recorded. Parents reported on their child's internalizing and externalizing behaviors using the Child Behavior Checklist (CBCL) four times over 1.5 years. Latent growth curve (LGC) modeling was conducted to assess neural and behavioral synchrony as predictors of internalizing and externalizing trajectories. Consistent with previous investigations in this age range, on average, internalizing and externalizing behaviors decreased over the four time points. Parent–child neural synchrony during a period of play predicted rate of change in internalizing but not externalizing behaviors such that higher parent–child neural synchrony was associated with a more rapid decrease in internalizing behaviors. Our results suggest that a parent–child dyad's ability to coordinate neural activation during positive interactions might serve as a protective mechanism in the context of internalizing behaviors.