Tom A. McAdams

Accounting for genetic and environmental confounds in associations between parent and child characteristics : a systematic review of children-of-twins studies

Parental psychopathology, parenting style, and the quality of intrafamilial relationships are all associated with child mental health outcomes. However, most research can say little about the causal pathways underlying these associations. This is because most studies are not genetically informative and are therefore not able to account for the possibility that associations are confounded by gene-environment correlation. That is, biological parents not only provide a rearing environment for their child, but also contribute 50% of their genes. Any associations between parental phenotype and child phenotype are therefore potentially confounded. One technique for disentangling genetic from environmental effects is the children-of-twins (COT) method. This involves using data sets comprising twin parents and their children to distinguish genetic from environmental associations between parent and child phenotypes. The COT technique has grown in popularity in the last decade, and we predict that this surge in popularity will continue. In the present article we explain the COT method for those unfamiliar with its use. We present the logic underlying this approach, discuss strengths and weaknesses, and highlight important methodological considerations for researchers interested in the COT method. We also cover variations on basic COT approaches, including the extended-COT method, capable of distinguishing forms of gene-environment correlation. We then present a systematic review of all the behavioral COT studies published to date. These studies cover such diverse phenotypes as psychosis, substance abuse, internalizing, externalizing, parenting, and marital difficulties. In reviewing this literature, we highlight past applications, identify emergent patterns, and suggest avenues for future research.

The Intergenerational Transmission of Anxiety: A Children-of-Twins Study

OBJECTIVE The transmission of anxiety within families is well recognized, but the underlying processes are poorly understood. Twin studies of adolescent anxiety demonstrate both genetic and environmental influence, and multiple aspects of parenting are associated with offspring anxiety. To date, the children-of-twins design has not been used to evaluate the relative contributions of genetic transmission compared with direct transmission of anxiety from parents to their offspring. METHOD Anxiety and neuroticism measures were completed by 385 monozygotic and 486 dizygotic same-sex twin families (37% male twin pair families) from the Twin and Offspring Study in Sweden. Structural equation models tested for the presence of both genetic and environmental transmission from one generation to the next. RESULTS For both anxiety and neuroticism, the models provide support for significant direct environmental transmission from parents to their adolescent offspring. In contrast, there was no evidence of significant genetic transmission. CONCLUSIONS The association between parental and offspring anxiety largely arises because of a direct association between parents and their children independent of genetic confounds. The lack of genetic transmission may reflect there being different genetic effects on these traits in adolescence and adulthood. Direct environmental transmission is in line with developmental theories of anxiety suggesting that children and adolescents learn anxious behaviors from their parents through a number of pathways such as modeling. Future analyses should combine children-of-twins data with child twin data in order to examine whether this direct effect solely represents parental influences on the offspring or whether it also includes child/adolescent anxiety evoking parental anxiety.

The relationship between parental depressive symptoms and offspring psychopathology: Evidence from a children-of-twins study and an adoption study

Background Parental depressive symptoms are associated with emotional and behavioural problems in offspring. However, genetically informative studies are needed to distinguish potential causal effects from genetic confounds, and longitudinal studies are required to distinguish parent-to-child effects from child-to-parent effects. Method We conducted cross-sectional analyses on a sample of Swedish twins and their adolescent offspring (n = 876 twin families), and longitudinal analyses on a US sample of children adopted at birth, their adoptive parents, and their birth mothers (n = 361 adoptive families). Depressive symptoms were measured in parents, and externalizing and internalizing problems measured in offspring. Structural equation models were fitted to the data. Results Results of model fitting suggest that associations between parental depressive symptoms and offspring internalizing and externalizing problems remain after accounting for genes shared between parent and child. Genetic transmission was not evident in the twin study but was evident in the adoption study. In the longitudinal adoption study child-to-parent effects were evident. Conclusions We interpret the results as demonstrating that associations between parental depressive symptoms and offspring emotional and behavioural problems are not solely attributable to shared genes, and that bidirectional effects may be present in intergenerational associations.

The Genesis 12-19 (G1219) Study: A Twin and Sibling Study of Gene-Environment Interplay and Adolescent Development in the UK

The Genesis 12-19 (G1219) Study is an ongoing longitudinal study of a sample of UK twin pairs, non-twin sibling pairs, and their parents. G1219 was initially designed to examine the role of gene-environment interplay in adolescent depression. However, since then data have continued to be collected from both parents and their offspring into young adulthood. This has allowed for longitudinal analyses of depression and has enabled researchers to investigate multiple phenotypes and to ask questions about intermediate mechanisms. The study has primarily focused on emotional development, particularly depression and anxiety, which have been assessed at multiple levels of analysis (symptoms, cognitions, and relevant environmental experiences). G1219 has also included assessment of a broader range of psychological phenotypes ranging from antisocial behaviors and substance use to sleep difficulties, in addition to multiple aspects of the environment. DNA has also been collected. The first wave of data collection began in the year 1999 and the fifth wave of data collection will be complete before the end of 2012. In this article, we describe the sample, data collection, and measures used. We also summarize some of the key findings to date.

Genes of Experience: Explaining the Heritability of Putative Environmental Variables Through Their Association with Behavioural and Emotional Traits

An increasing body of evidence shows that many ‘environmental’ measures are heritable, indicating genetic involvement in environmental exposure (or gene–environment correlation). In the present study we attempt to clarify why three such ‘environmental’ measures (maternal negativity, paternal negativity and negative life events) are consistently found to be heritable. Through multivariate genetic analysis of a sample of adolescent twins from the UK we show that the heritability of these putative environmental measures can be explained via their association with five behavioural phenotypes: oppositionality, delinquency, physical aggression, depression and anxiety. This is consistent with the notion that being genetically susceptible to certain behavioural difficulties could lead to exposure to certain life events, and this may account for the reported heritability of ‘environmental’ measures. Results are discussed in the context of possible active, evocative and passive gene–environment correlations.

Attentional threat avoidance and familial risk are independently associated with childhood anxiety disorders

BACKGROUND  Twin studies in children reveal that familial aggregation of anxiety disorders is due to both genetic and environmental factors. Cognitive biases for threat information are considered a robust characteristic of childhood anxiety. However, little is known regarding the underlying aetiology of such biases and their role in anxiety disorders. METHOD  A face version of the dot-probe task measuring attentional biases for negative (anger, fear, sad, disgust) and positive (happy) facial expressions was completed by 600, 8-year-old twins; the largest study of its kind. Twin correlations for attentional bias scores were compared to estimate genetic and environmental effects. Parent-report diagnostic interviews identified children with an anxiety disorder. Indices of inferred genetic and familial risk for anxiety disorders were created for each child. Data were analysed using a series of logistic regressions. RESULTS Anxious children showed greater attentional avoidance of negative faces than nonanxious children; t (548) = 2.55, p < .05. Attentional avoidance was not under genetic or shared environmental influence. Risk for anxiety disorders was predicted by familial factors. Both attentional avoidance and inferred familial risk were significant but independent predictors of anxiety disorders (ORs = .65 and 3.64, respectively). CONCLUSIONS Anxiety-related attentional biases and familial risk play important but independent roles in childhood anxiety disorders. If replicated, these findings indicate that links between genetic risk and anxiety disorders lie outside the domain of attentional processes.

Aetiological overlap between obsessive–compulsive and depressive symptoms: a longitudinal twin study in adolescents and adults

Background Depression is commonly co-morbid with obsessive–compulsive disorder (OCD). However, it is unknown whether depression is a functional consequence of OCD or whether these disorders share a common genetic aetiology. This longitudinal twin study compared these two hypotheses. Method Data were drawn from a longitudinal sample of adolescent twins and siblings (n = 2651; Genesis 12–19 study) and from a cross-sectional sample of adult twins (n = 4920). The longitudinal phenotypic associations between OCD symptoms (OCS) and depressive symptoms were examined using a cross-lag model. Multivariate twin analyses were performed to explore the genetic and environmental contributions to the cross-sectional and longitudinal relationship between OCS and depressive symptoms. Results In the longitudinal phenotypic analyses, OCS at time 1 (wave 2 of the Genesis 12–19 study) predicted depressive symptoms at time 2 (wave 3 of the Genesis 12–19 study) to a similar extent to which depressive symptoms at time 1 predicted OCS at time 2. Cross-sectional twin analyses in both samples indicated that common genetic factors explained 52–65% of the phenotypic correlation between OCS and depressive symptoms. The proportion of the phenotypic correlation due to common non-shared environmental factors was considerably smaller (35%). In the adolescent sample, the longitudinal association between OCS at time 1 and subsequent depressive symptoms was accounted for by the genetic association between OCS and depressive symptoms at time 1. There was no significant environmental association between OCS and later depressive symptoms. Conclusions The present findings show that OCS and depressive symptoms co-occur primarily due to shared genetic factors and suggest that genetic, rather than environmental, effects account for the longitudinal relationship between OCS and depressive symptoms.

Maternal perinatal and concurrent depressive symptoms and child behavior problems: a sibling comparison study

Background Previous studies have found significant associations between maternal prenatal and postpartum depression and child behavior problems (CBP). The present study investigates whether associations remain in a prospective, longitudinal design adjusted for familial confounding. Methods The sample comprised 11,599 families including 17,830 siblings from the Norwegian Mother and Child Cohort study. Mothers reported depressive symptoms at gestational weeks 17 and 30, as well as 6 months, 1.5, 3, and 5 years postpartum. Fathers’ depression was measured at gestational week 17. At the last three time‐points, child internalizing and externalizing problems were concurrently assessed. We performed multilevel analyses for internalizing and externalizing problems separately, using parental depression as predictors. Analyses were repeated using a sibling comparison design to adjust for familial confounding. Results All parental depressive time‐points were significantly and positively associated with child internalizing and externalizing problems. After sibling comparison, however, only concurrent maternal depression was significantly associated with internalizing [estimate = 2.82 (1.91–3.73, 95% CI)] and externalizing problems [estimate = 2.40 (1.56–3.23, 95% CI)]. The effect of concurrent maternal depression on internalizing problems increased with child age. Conclusions Our findings do not support the notion that perinatal maternal depression is particularly detrimental to childrens psychological development, as the most robust effects were found for maternal depression occurring during preschool years.

Aetiological influences on stability and change in emotional and behavioural problems across development: a systematic review

Emotional and behavioural problems in childhood and adolescence can be chronic and are predictive of future psychiatric problems. Understanding what factors drive the development and maintenance of these problems is therefore crucial. Longitudinal behavioural genetic studies using twin, sibling or adoption data can be used to explore the developmental aetiology of stability and change in childhood and adolescent psychopathology. We present a systematic review of longitudinal, behavioural genetic analyses of emotional and behavioural problems between ages 0 to 18 years. We identified 58 studies, of which 19 examined emotional problems, 30 examined behavioural problems, and 9 examined both. In the majority of studies, stability in emotional and behavioural problems was primarily genetically influenced. Stable environmental factors were also widely found, although these typically played a smaller role. Both genetic and environmental factors were involved in change across development. We discuss the findings in the context of the wider developmental literature and make recommendations for future research.

Aetiological overlap between anxiety and attention deficit hyperactivity symptom dimensions in adolescence

Background Anxiety and attention‐deficit/hyperactivity (ADH) problems are common in adolescence, often co‐occur, and are characterised by high heterogeneity in their phenotypic expressions. Although it is known that anxiety and ADH problems correlate, the relationships between subtypes of anxiety and ADH problems have been scarcely investigated. Methods Using a large population sample of adolescent twins and siblings we explored the phenotypic and aetiological association between anxiety subtypes (panic/agoraphobia, separation anxiety, social anxiety, physical injury fears, obsessive‐compulsive symptoms and generalised anxiety) and the two ADH dimensions (attention problems and hyperactivity/impulsivity). Both phenotypes were assessed using self‐report questionnaires. Results The association between ADH problems and anxiety could be entirely attributed to attention problems, not hyperactivity/impulsivity. Most of the correlations between anxiety subtypes and attention problems showed an approximately equal role of genetic and nonshared environmental factors. Conclusions The high heterogeneity within anxiety and ADH problems should be taken into account in order to better understand comorbidity between them.