Developmental change in the association between adolescent depressive symptoms and the home environment: results from a longitudinal, genetically informative investigation

Background: Depression is already highly prevalent by late adolescence, indicating that research into its developmental emergence should consider earlier risk factors and environmental contexts. The home environment is a key context for children and adolescents throughout development. However, the nature of relationships that exist between aspects of the home environment and the development of depressive symptoms cannot be assumed. Genetically informative studies have been used to provide insights about the aetiology of such relationships, often finding them to be partly confounded by the influence of children's genes. Here, we investigate developmental change in the aetiology of the association between aspects of the home environment and depressive symptoms at the onset of adolescence. Methods: We used longitudinal child‐ and parent‐report data from >5,000 twin pairs enrolled in the UK‐representative Twins Early Development Study. Multivariate, genetically sensitive structural equation models were used to decompose latent variance and covariance in depressive symptoms (measured at 12 and 16 years) and aspects of the home environment (at 9 and 14 years) into genetic and environmental influences. Results: Going from childhood to adolescence, genetic influences accounted for an increasing proportion of the association [30% (16–42) of r = .44 in childhood; 40% (25–61) of r = .43 in adolescence], at the expense of shared environmental influences, which decreased from 70% (58–83) to 48% (29–62). Unique environmental influences accounted for a significant proportion of the association in adolescence only [12% (06–18)]. Developmental changes could largely be attributed to subtle shifts in the relative importance of stable aetiological factors, rather than the emergence of influences unique to adolescence. Conclusions: These findings emphasise the importance of developmental and aetiological context in interpreting associations between aspects of the home environment and child emotional outcomes

Etiological influences on perceptions of parenting: A longitudinal, multi-informant twin study

Children and their parents often differ in their perception of the relationship they share. As this relationship changes developmentally, the nature of these differences may also change. Longitudinal genetic designs can be used to investigate the developmental etiologies of shared and distinct perceptions. In this study, we used longitudinal psychometric models to analyze child and parent reports of negative parenting for 6417 twin pairs from the Twins Early Development Study at ages 9, 12 and 14 years. Within-time cross-reporter correlations, indicating the degree to which children and parents perceived negative parenting behaviors similarly at each age, were moderate (r = .44 − .46). Longitudinal genetic analyses revealed these shared perceptions to be relatively stable during the transition into adolescence, with this stability driven by a combination of children’s genetic factors and family-wide environmental factors. In contrast, child- and parent-specific perceptions of parenting were predominantly age-specific, a developmental pattern underpinned by child genetic factors and a combination of family-wide and unique environmental influences. These results and their implications are discussed in the context of interplay between reciprocal interactions, subjective insight and developmental behavioral change in the parent–child relationship

Genetics of co-developing conduct and emotional problems during childhood and adolescence

Common genetic influences offer a partial explanation for comorbidity between different psychiatric disorders1,2,3. However, the genetics underlying co-development—the cross-domain co-occurrence of patterns of change over time—of psychiatric symptoms during childhood and adolescence has not been well explored. Here, we show genetic influence on joint symptom trajectories of parent-reported conduct and emotional problems (overall N = 15,082) across development (4–16 years) using both twin- and genome-wide polygenic score analyses (genotyped N = 2,610). Specifically, we found seven joint symptom trajectories, including two characterized by jointly stable and jointly increasing symptoms of conduct and emotional problems, respectively (7.3% of the sample, collectively). Twin modelling analyses revealed substantial genetic influence on trajectories (heritability estimates range of 0.41–0.78). Furthermore, individuals’ risk of being classified in the most symptomatic trajectory classes was significantly predicted by polygenic scores for years-of-education-associated alleles and depressive symptoms-associated alleles. Complementary analyses of child self-reported symptoms across late childhood and early adolescence yielded broadly similar results. Taken together, our results indicate that genetic factors are involved in the co-development of conduct and emotional problems across childhood and adolescence, and that individuals with co-developing symptoms across multiple domains may represent a clinical subgroup characterized by increased levels of genetic risk

Measuring Health Spillovers for Economic Evaluation: A Case Study in Meningitis

The health of carers and others close to the patient will often be relevant to economic evaluation, but it is very rarely considered in practice. This may reflect a lack of understanding of how the spillover effect of illness can be appropriately quantified. In this study we used three different approaches to quantify health spillovers resulting from meningitis. We conducted a survey of 1218 family networks affected by meningitis and used regression modelling to estimate spillover effects. The findings show that meningitis had long-term effects on family members' health, particularly affecting the likelihood of family members reporting anxiety and depression. These effects extended beyond a single close family member. These findings suggest that vaccinating against meningitis will bring significant health benefits not just to those that might have contracted the illness but also to their family networks. In methodological terms, different approaches for quantifying health spillovers provided broadly consistent results. The choice of method will be influenced by the ease of collecting primary data from family members in intervention contexts

Maternal prenatal depressive symptoms and risk for early-life psychopathology in offspring: results from a genetically-informative, population-based sample

Background: Maternal prenatal depression is a known risk factor for early-life psychopathology among offspring; however, potential risk transmission mechanisms need to be distinguished. We aimed to test the relative importance of passive genetic transmission, direct exposure, and indirect exposure in the association between maternal prenatal depressive symptoms and early-life internalising and externalising psychopathology in offspring. Methods: We used structural equation modelling of phenotypic data and genetically informative relationships from the families of participants in the Norwegian Mother and Child Birth Cohort Study (MoBa). The analytic subsample of MoBa used in the current study comprises 22 195 mothers and 35 299 children. We used mothers' self-reported depressive symptoms during pregnancy, as captured by the Symptom Checklist, and their reports of symptoms of psychopathology in their offspring during the first few years of life (measured at 18, 36, and 60 months using the Child Behavior Checklist). Findings: Maternal prenatal depressive symptoms were found to be associated with early-life psychopathology primarily via intergenerationally shared genetic factors, which explained 41% (95% CI 36–46) of variance in children's internalising problems and 37% (30–44) of variance in children's externalising problems. For internalising problems, phenotypic transmission also contributed significantly, accounting for 14% (95% CI 5–19) of the association, but this contribution was found to be explained by exposure to concurrent maternal depressive symptoms, rather than by direct exposure in utero. Interpretation: Associations between maternal prenatal depressive symptoms and offspring behavioural outcomes in early childhood are likely to be at least partially explained by shared genes. This genetic confounding should be considered when attempting to quantify risks posed by in-utero exposure to maternal depressive symptoms. Funding: UK Economic and Social Research Council, Norwegian Research Council, Norwegian Ministries of Health and Care Services, and Education & Research, Wellcome Trust, Royal Society, and National Institute for Health Research

Modeling assortative mating and genetic similarities between partners, siblings, and in-laws

Assortative mating on heritable traits can have implications for the genetic resemblance between siblings and in-laws in succeeding generations. We studied polygenic scores and phenotypic data from pairs of partners (n = 26,681), siblings (n = 2,170), siblings-in-law (n = 3,905), and co-siblings-in-law (n = 1,763) in the Norwegian Mother, Father and Child Cohort Study. Using structural equation models, we estimated associations between measurement error-free latent genetic and phenotypic variables. We found evidence of genetic similarity between partners for educational attainment (rg = 0.37), height (rg = 0.13), and depression (rg = 0.08). Common genetic variants associated with educational attainment correlated between siblings above 0.50 (rg = 0.68) and between siblings-in-law (rg = 0.25) and co-siblings-in-law (rg = 0.09). Indirect assortment on secondary traits accounted for partner similarity in education and depression, but not in height. Comparisons between the genetic similarities of partners and siblings indicated that genetic variances were in intergenerational equilibrium. This study shows genetic similarities between extended family members and that assortative mating has taken place for several generations.publishedVersio

Examining intergenerational risk factors for conduct problems using polygenic scores in the Norwegian Mother, Father and Child Cohort Study

The aetiology of conduct problems involves a combination of genetic and environmental factors, many of which are inherently linked to parental characteristics given parents' central role in children's lives across development. It is important to disentangle to what extent links between parental heritable characteristics and children's behaviour are due to transmission of genetic risk or due to parental indirect genetic influences via the environment (i.e., genetic nurture). We used 31,290 genotyped mother-father-child trios from the Norwegian Mother, Father and Child Cohort Study (MoBa), testing genetic transmission and genetic nurture effects on conduct problems using 13 polygenic scores (PGS) spanning psychiatric conditions, substance use, education-related factors, and other risk factors. Maternal or self-reports of conduct problems at ages 8 and 14 years were available for up to 15,477 children. We found significant genetic transmission effects on conduct problems for 12 out of 13 PGS at age 8 years (strongest association: PGS for smoking, β = 0.07, 95% confidence interval = [0.05, 0.08]) and for 4 out of 13 PGS at age 14 years (strongest association: PGS for externalising problems, β = 0.08, 95% confidence interval = [0.05, 0.11]). Conversely, we did not find genetic nurture effects for conduct problems using our selection of PGS. Our findings provide evidence for genetic transmission in the association between parental characteristics and child conduct problems. Our results may also indicate that genetic nurture via traits indexed by our polygenic scores is of limited aetiological importance for conduct problems-though effects of small magnitude or effects via parental traits not captured by the included PGS remain a possibility

Early manifestations of genetic risk for neurodevelopmental disorders

Background: Attention deficit/hyperactivity disorder (ADHD), autism spectrum disorder (autism) and schizophrenia are highly heritable neurodevelopmental disorders, affecting the lives of many individuals. It is important to increase our understanding of how the polygenic risk for neurodevelopmental disorders manifests during childhood in boys and girls. Methods: Polygenic risk scores (PRS) for ADHD, autism and schizophrenia were calculated in a subsample of 15 205 children from the Norwegian Mother, Father and Child Cohort Study (MoBa). Mother-reported traits of repetitive behavior, social communication, language and motor difficulties, hyperactivity and inattention were measured in children at 6 and 18 months, 3, 5 and 8 years. Linear regression models in a multigroup framework were used to investigate associations between the three PRS and dimensional trait measures in MoBa, using sex as a grouping variable. Results: Before the age of 2, the ADHD PRS was robustly associated with hyperactivity and inattention, with increasing strength up to 8 years, and with language difficulties at age 5 and 8. The autism PRS was robustly associated with language difficulties at 18 months, motor difficulties at 36 months, and hyperactivity and inattention at 8 years. We did not identify robust associations for the schizophrenia PRS. In general, the PRS associations were similar in boys and girls. The association between ADHD PRS and hyperactivity at 18 months was, however, stronger in boys. Conclusions: Polygenic risk for autism and ADHD in the general population manifests early in childhood and broadly across behavioral measures of neurodevelopmental traits.publishedVersio