Genetic and environmental contributions to individual differences in visual attention and oculomotor control in early infancy.

Infants differ in their level of eye movement control, which at the extreme could be linked to autism. We assessed eye movements in 450 twins (225 pairs, 57% monozygotic, 46% female, aged 5-6 months) using the gap-overlap eye-tracking task. Shorter latency in the gap condition was associated with having more parent-rated autistic traits at 2 years. Latency across the task's three conditions was primarily explained by one highly heritable latent factor likely representing individual differences in basic oculomotor efficiency and/or in visual information processing. Additionally, disengagement of attention was linked to unique genetic factors, suggesting that genetic factors involved in visual attention are different from those involved in basic visual information processing and oculomotor efficiency.

Parent-child interaction at age 5 months: genetic and environmental contributions and associations with later socio-communicative development.

BACKGROUND: Characteristics of parent-child interaction (PCI) early in life have been associated with later development in the child. Twin studies can help to disentangle child contributions to parent-child interaction, for example, by assessing the influence of the child's genetics on his/her social environment, which includes parental behaviour. METHODS: Infant twins from a community sample [354 monozygotic (MZ), 268 same-sex dizygotic (DZ)] were assessed in terms of PCI at age 5 months. We used the classical twin design to map the aetiology of several parent and child PCI scales and their covariation. We investigated the relations between PCI and later parent-rated child's social communication, language, and autistic traits at ages 2 and 3. RESULTS: Heritability was below 20% for all the included PCI traits. Unique (nonshared) environmental influences substantially overlapped across several PCI scales, suggesting that idiosyncrasies linked to each session shaped the scoring of several traits in a systematic way. Factor analysis revealed three uncorrelated latent factors, which were conceptualized as 'child negative affect', 'positive affective interaction', and 'parent's supportive strategies'. Parents who were rated highly on 'sensitive responsiveness' at 5 months tended to rate their offspring higher in terms of socio-communicative and language development and lower in terms of autistic traits in the second and third years of life. CONCLUSIONS: This study maps the phenotypic and aetiological structure of PCI in early infancy and supports the view that parents' sensitive responsiveness towards their infant is associated with later developmental gains in several domains. We did not find strong evidence of any so-called evocative genetic effects on parents' behaviour. We discuss the results considering the general challenge for lab-based observational PCI measures to capture the richness of parent-child interaction.

An axis of genetic heterogeneity in autism is indexed by age at diagnosis and is associated with varying developmental and mental health profiles.

There is growing recognition that earliest signs of autism need not clearly manifest in the first three years of life. To what extent is this variation in developmental trajectories associated with age at autism diagnosis? Does the genetic profile of autism vary with age at autism diagnosis? Using longitudinal data from four birth cohorts, we demonstrate that two different trajectories of socio-emotional behaviours are associated with age at diagnosis. We further demonstrate that the age at autism diagnosis is partly heritable (h2 SNP = 0.12, s.e.m = 0.01), and is associated with two moderately correlated (rg = 0.38, s.e.m = 0.07) autism polygenic factors. One of these factors is associated with earlier diagnosis of autism, lower social and communication abilities in early childhood. The second factor is associated with later autism diagnosis, increased socio-emotional difficulties in adolescence, and has moderate to high positive genetic correlations with Attention-Deficit/Hyperactivity Disorder, mental health conditions, and trauma. Overall, our research identifies an axis of heterogeneity in autism, indexed by age at diagnosis, which partly explains heterogeneity in autism and the profiles of co-occurring neurodevelopmental and mental health profiles. Our findings have important implications for how we conceptualise autism and provide one model to explain some of the diversity within autism.

A systematic review and meta-analysis of the associations between motor milestone timing and motor development in neurodevelopmental conditions.

Early motor skills may be important early markers of neurodevelopmental conditions or predictors of their later onset. To explore this, we conducted a systematic review and meta-analysis of infant motor skill assessments in those who go on to gain a clinical diagnosis of autism, attention deficit hyperactivity disorder (ADHD), schizophrenia, language conditions, tic disorders, or developmental coordination disorder (DCD). In total, 63 articles met inclusion criteria. Three three-level meta-analyses were run. Meta-analysis of milestone achievement in N= 21205 individuals revealed gross motor milestones were significantly delayed compared to controls (g= 0.53, p< 0.001). Subgroup analyses revealed autism (g= 0.63) and DCD (g= 0.53) had the highest magnitude delays. Specific delays were revealed for holding the head up (g= 0.21), sitting (g= 0.28), standing (g= 0.35), crawling (g= 0.19), and walking (g= 0.71). Meta-analyses of standardised motor skill measurements in N= 1976 individuals revealed reduced performance compared to controls in autism and language conditions (g= -0.54, p< 0.001). Together, these findings demonstrate delayed milestone attainment and motor impairments in early childhood in neurodevelopmental conditions.

The potential and translational application of infant genetic research.

In the current genomic revolution, the infancy life stage is the most neglected. Although clinical genetics recognizes the value of early identification in infancy of rare genetic causes of disorders and delay, common genetic variation is almost completely ignored in research on infant behavioral and neurodevelopmental traits. In this Perspective, we argue for a much-needed surge in research on common genetic variation influencing infant neurodevelopment and behavior, findings that would be relevant for all children. We now see convincing evidence from different research designs to suggest that developmental milestones, skills and behaviors of infants are heritable and thus are suitable candidates for gene-discovery research. We highlight the resources available to the field, including genotyped infant cohorts, and we outline, with recommendations, special considerations needed for infant data. Therefore, infant genetic research has the potential to impact basic science and to affect educational policy, public health and clinical practice.

Evocative effects on the early caregiving environment of genetic factors underlying the development of intellectual and academic ability.

This study examined gene-environment correlation (rGE) in intellectual and academic development in 561 U.S.-based adoptees (57% male; 56% non-Latinx White, 19% multiracial, 13% Black or African American, 11% Latinx) and their birth and adoptive parents between 2003 and 2017. Birth mother intellectual and academic performance predicted adoptive mother warmth at child age 6 (ß = .14, p = .038) and 7 (ß = .12, p = .040) but not 4.5 years, and adoptive father warmth at 7 (ß = .18, p = .007) but not 4.5 or 6 years. These rGE effects were not mediated by children's language. Contrary to theory that rGE accounts for increasing heritability of intellectual ability, parenting did not mediate genetic effects on children's language or academic performance.

Perinatal risk factors and subclinical hypomania: A prospective community study.

BACKGROUND: Perinatal risk factors are implicated in the development of psychopathology, but their role in bipolar disorder (BD) and hypomania is unclear. Using data from a prospective community cohort, this is the first study to investigate the association between a range of perinatal risk factors, hypomanic symptoms, and 'high-risk' for BD in the general population. METHODS: Parent report of perinatal events were available for 26,040 eighteen-month-olds from the Twins Early Development Study. Subsequent self-report hypomania was measured at ages 16 (Hypomania Checklist-16; N = 2943) and 26 (Mood Disorders Questionnaire; N = 7748). Participants were categorised as 'high-risk' for BD using established classifications. Linear and logistic regressions were conducted within a generalised estimating equations framework to account for relatedness in the sample. RESULTS: Prenatal alcohol exposure (ß = 0.08, SE = 0.04, p = .0002) and number of alcohol units consumed (ß = 0.09, SE = 0.02, p < .0001) were associated with hypomanic symptoms at age 16, and number of alcohol units (OR = 1.13, 95 % CI:1.06-1.21, p = .0003) and maternal stress (OR = 1.68, 95 % CI:1.21-2.34, p = .002) were associated with 'high-risk' for BD age 16. Prenatal tobacco exposure (ß = 0.10, SE = 0.04, p < .0001) and number of cigarettes smoked (ß = 0.10, SE = 0.01, p < .0001) were associated with hypomanic symptoms and 'high-risk' for BD at age 26, although these result were attenuated controlling for parental psychiatric history. LIMITATIONS: Familial confounding could not be fully adjusted for. Rater reports include some biases. CONCLUSIONS: These findings show perinatal risk factors to be associated with subclinical hypomania and 'high-risk' for BD. Future work should explore the mechanisms underlying these longitudinal associations, which could shed light on prevention and intervention efforts.

Genetic and phenotypic heterogeneity in early neurodevelopmental traits in the Norwegian Mother, Father and Child Cohort Study.

BACKGROUND: Autism and different neurodevelopmental conditions frequently co-occur, as do their symptoms at sub-diagnostic threshold levels. Overlapping traits and shared genetic liability are potential explanations. METHODS: In the population-based Norwegian Mother, Father, and Child Cohort study (MoBa), we leverage item-level data to explore the phenotypic factor structure and genetic architecture underlying neurodevelopmental traits at age 3 years (N = 41,708-58,630) using maternal reports on 76 items assessing children's motor and language development, social functioning, communication, attention, activity regulation, and flexibility of behaviors and interests. RESULTS: We identified 11 latent factors at the phenotypic level. These factors showed associations with diagnoses of autism and other neurodevelopmental conditions. Most shared genetic liabilities with autism, ADHD, and/or schizophrenia. Item-level GWAS revealed trait-specific genetic correlations with autism (items rg range = - 0.27-0.78), ADHD (items rg range = - 0.40-1), and schizophrenia (items rg range = - 0.24-0.34). We find little evidence of common genetic liability across all neurodevelopmental traits but more so for several genetic factors across more specific areas of neurodevelopment, particularly social and communication traits. Some of these factors, such as one capturing prosocial behavior, overlap with factors found in the phenotypic analyses. Other areas, such as motor development, seemed to have more heterogenous etiology, with specific traits showing a less consistent pattern of genetic correlations with each other. CONCLUSIONS: These exploratory findings emphasize the etiological complexity of neurodevelopmental traits at this early age. In particular, diverse associations with neurodevelopmental conditions and genetic heterogeneity could inform follow-up work to identify shared and differentiating factors in the early manifestations of neurodevelopmental traits and their relation to autism and other neurodevelopmental conditions. This in turn could have implications for clinical screening tools and programs.

Editorial: Are government early years learning and development frameworks evidence-based? A scientist's perspective.

Not all young children attend nurseries, childminders or other group settings before they start school, but many do. It is common for countries to set out a framework to guide practice for early years providers (such as nurseries) to follow. The conundrum regarding these frameworks for young children is that proving evidence of a causal link between early environments and later outcomes is very challenging scientifically. So how do governments choose what learning and development practices and goals to make mandatory for childcare providers? And is it realistic to expect early years providers to meet the legal requirements that these frameworks impose? We do not know which learning and development practices impact positively on later outcomes, and we certainly do not know if there is a one-size-fits-all approach for an early years framework that is guaranteed to work.

Genetics of environmental sensitivity and its association with variations in emotional problems, autistic traits, and wellbeing.

Greater environmental sensitivity has been associated with increased risk of mental health problems, especially in response to stressors, and lower levels of subjective wellbeing. Conversely, sensitivity also correlates with lower risk of emotional problems in the absence of adversity, and in response to positive environmental influences. Additionally, sensitivity has been found to correlate positively with autistic traits. Individual differences in environmental sensitivity are partly heritable, but it is unknown to what extent the aetiological factors underlying sensitivity overlap with those on emotional problems (anxiety and depressive symptoms), autistic traits and wellbeing. The current study used multivariate twin models and data on sensitivity, emotional problems, autistic traits, and several indices of psychological and subjective wellbeing, from over 2800 adolescent twins in England and Wales. We found that greater overall sensitivity correlated with greater emotional problems, autistic traits, and lower subjective wellbeing. A similar pattern of correlations was found for the Excitation and Sensory factors of sensitivity, but, in contrast, the Aesthetic factor was positively correlated with psychological wellbeing, though not with emotional problems nor autistic traits. The observed correlations were largely due to overlapping genetic influences. Importantly, genetic influences underlying sensitivity explained between 2 and 12% of the variations in emotional problems, autistic traits, and subjective wellbeing, independent of trait-specific or overlapping genetic influences. These findings encourage incorporating the genetics of environmental sensitivity in future genomic studies aiming to delineate the heterogeneity in emotional problems, autistic traits, and wellbeing.

Sustained looking at faces at 5 months of age is associated with socio-communicative skills in the second year of life.

Efficiently processing information from faces in infancy is foundational for nonverbal communication. We studied individual differences in 5-month-old infants' (N = 517) sustained attention to faces and preference for emotional faces. We assessed the contribution of genetic and environmental influences to individual differences in these gaze behaviors, and the association between these traits and other concurrent and later phenotypes. We found an association between the mean duration of looking at a face (before looking away from it) at 5 months and socio-communicative abilities at 14 months (ß = 0.17, 95% CI: 0.08; 0.26, p < 0.001). Sustained attention to faces predicted socio-communicative abilities over and above variance captured by mean fixation duration. We also found a statistically significant but weak tendency to prefer looking at smiling faces (relative to neutral faces), but no indication that variability in this behavior was explained by genetic effects. Moderate heritability was found for sustained attention to faces (A = 0.23, CI: 0.06; 0.38), while shared environmental influences were non-significant for both phenotypes. These findings suggest that sustained looking at individual faces before looking away is a developmentally significant 'social attention' phenotype in infancy, characterized by moderate heritability and a specific relation to later socio-communicative abilities.

Phenotypic and Genetic Associations Between Preschool Fine Motor Skills and Later Neurodevelopment, Psychopathology, and Educational Achievement.

BACKGROUND: Fine motor skills are heritable and comprise important milestones in development, and some evidence suggests that impairments in fine motor skills are associated with neurodevelopmental conditions, psychiatric disorders, and poor educational outcomes. METHODS: In a preregistered study of 9625 preschool children from TEDS (Twins Early Development Study), fine motor assessments (drawing, block building, folding, and questionnaires) were conducted at 2, 3, and 4 years of age. A cross-age fine motor score was derived using principal component analysis. Multivariate regression analysis was used to examine the relationships between the fine motor score and neurodevelopmental traits, psychopathology, and educational outcomes at 3 later ages (7-8, 12, and 16 years) and cross-age psychopathology composite scores. Polygenic scores (PGSs) were created for attention-deficit/hyperactivity disorder (ADHD), autism, schizophrenia, anxiety, major depressive disorder, obsessive-compulsive disorder, and years of education. We ran single-PGS models and a multi-PGS model. RESULTS: Fine motor skills were negatively associated with neurodevelopmental traits and psychopathology across childhood and adolescence and positively associated with educational achievement in adolescence (ß = 0.25, p < .001). Superior fine motor skills were associated with a higher years-of-education PGS (ß = 0.07, p < .001), a lower ADHD PGS (ß = -0.04, p = .011), and a higher anxiety PGS (ß = 0.03, p = .040). Similarly, the multi-PGS model retained the PGSs for years of education (ß = 0.07), ADHD (ß = -0.03), and anxiety (ß = 0.01). A non-preregistered analysis in an independent preschool sample replicated the ADHD PGS association, but not the years of education or anxiety PGS associations. CONCLUSIONS: Fine motor skills are linked genetically and phenotypically to later neurodevelopment, psychopathology, and educational outcomes. Future work should investigate the mechanisms that underlie the role of fine motor development in later outcomes.

Infants' looking preferences for social versus non-social objects reflect genetic variation.

To what extent do individual differences in infants' early preference for faces versus non-facial objects reflect genetic and environmental factors? Here in a sample of 536 5-month-old same-sex twins, we assessed attention to faces using eye tracking in two ways: initial orienting to faces at the start of the trial (thought to reflect subcortical processing) and sustained face preference throughout the trial (thought to reflect emerging attention control). Twin model fitting suggested an influence of genetic and unique environmental effects, but there was no evidence for an effect of shared environment. The heritability of face orienting and preference were 0.19 (95% confidence interval (CI) 0.04 to 0.33) and 0.46 (95% CI 0.33 to 0.57), respectively. Face preference was associated positively with later parent-reported verbal competence (ß = 0.14, 95% CI 0.03 to 0.25, P = 0.014, R2 = 0.018, N = 420). This study suggests that individual differences in young infants' selection of perceptual input-social versus non-social-are heritable, providing a developmental perspective on gene-environment interplay occurring at the level of eye movements.

Sub-types of insomnia in adolescents: Insights from a quantitative/molecular twin study.

Background: Insomnia with short sleep duration has been postulated as more severe than that accompanied by normal/long sleep length. While the short duration subtype is considered to have greater genetic influence than the other subtype, no studies have addressed this question. This study aimed to compare these subtypes in terms of: (1) the heritability of insomnia symptoms; (2) polygenic scores (PGS) for insomnia symptoms and sleep duration; (3) the associations between insomnia symptoms and a wide variety of traits/disorders. Methods: The sample comprised 4000 pairs of twins aged 16 from the Twins Early Development Study. Twin models were fitted to estimate the heritability of insomnia in both groups. PGS were calculated for self-reported insomnia and sleep duration and compared among participants with short and normal/long sleep duration. Results: Heritability was not significantly different in the short sleep duration group (A = 0.13 [95%CI = 0.01, 0.32]) and the normal/long sleep duration group (A = 0.35 [95%CI = 0.29, 0.40]). Shared environmental factors accounted for a substantial proportion of the variance in the short sleep duration group (C = 0.19 [95%CI = 0.05, 0.32]) but not in the normal/long sleep duration group (C = 0.00 [95%CI = 0.00, 0.04]). PGS did not differ significantly between groups although results were in the direction expected by the theory. Our results also showed that insomnia with short (as compared to normal/long) sleep duration had a stronger association with anxiety and depression (p < .05)-although not once adjusting for multiple testing. Conclusions: We found mixed results in relation to the expected differences between the insomnia subtypes in adolescents. Future research needs to further establish cut-offs for 'short' sleep at different developmental stages and employ objective measures of sleep.

Editorial: What's in a name? Drawing on the examples of autism and schizophrenia, some reflections on diagnostic labels and their future role in child and adolescent psychiatry.

Ten years have passed since the release of DSM-5, which brought with it some notable changes in diagnostic labels. In this editorial, the impact of labels, and the changes in labels used in child and adolescent psychiatry, are discussed, with examples drawn from autism and schizophrenia. The diagnostic labels that children and adolescents receive feed into their treatment access and future potential but also to their self-identities. Outside of medicine, extensive budgets and time are spent to test how consumers identify with the labels of products. Diagnoses are not commercial products, of course, but the choice of labels used in child and adolescent psychiatry should remain a priority, in light of their impact on translational science, treatment and on individuals, alongside the ever-evolving nature of language itself.

Developmental milestones in early childhood and genetic liability to neurodevelopmental disorders.

BACKGROUND: Timing of developmental milestones, such as age at first walking, is associated with later diagnoses of neurodevelopmental disorders. However, its relationship to genetic risk for neurodevelopmental disorders in the general population is unknown. Here, we investigate associations between attainment of early-life language and motor development milestones and genetic liability to autism, attention deficit hyperactivity disorder (ADHD), and schizophrenia. METHODS: We use data from a genotyped sub-set (N = 25699) of children in the Norwegian Mother, Father and Child Cohort Study (MoBa). We calculate polygenic scores (PGS) for autism, ADHD, and schizophrenia and predict maternal reports of children's age at first walking, first words, and first sentences, motor delays (18 months), and language delays and a generalised measure of concerns about development (3 years). We use linear and probit regression models in a multi-group framework to test for sex differences. RESULTS: We found that ADHD PGS were associated with earlier walking age (ß = -0.033, padj < 0.001) in both males and females. Additionally, autism PGS were associated with later walking (ß = 0.039, padj = 0.006) in females only. No robust associations were observed for schizophrenia PGS or between any neurodevelopmental PGS and measures of language developmental milestone attainment. CONCLUSIONS: Genetic liabilities for neurodevelopmental disorders show some specific associations with the age at which children first walk unsupported. Associations are small but robust and, in the case of autism PGS, differentiated by sex. These findings suggest that early-life motor developmental milestone attainment is associated with genetic liability to ADHD and autism in the general population.

Global motion processing in infants' visual cortex and the emergence of autism.

Autism is a heritable and common neurodevelopmental condition, with behavioural symptoms typically emerging around age 2 to 3 years. Differences in basic perceptual processes have been documented in autistic children and adults. Specifically, data from many experiments suggest links between autism and alterations in global visual motion processing (i.e., when individual motion information is integrated to perceive an overall coherent pattern). Yet, no study has investigated whether a distinctive organization of global motion processing precede the emergence of autistic symptoms in early childhood. Here, using a validated infant electroencephalography (EEG) experimental paradigm, we first establish the normative activation profiles for global form, global motion, local form, and local motion in the visual cortex based on data from two samples of 5-month-old infants (total n = 473). Further, in a sample of 5-month-olds at elevated likelihood of autism (n = 52), we show that a different topographical organization of global motion processing is associated with autistic symptoms in toddlerhood. These findings advance the understanding of neural organization of infants' basic visual processing, and its role in the development of autism.

A meta-analysis of genetic effects associated with neurodevelopmental disorders and co-occurring conditions.

A systematic understanding of the aetiology of neurodevelopmental disorders (NDDs) and their co-occurrence with other conditions during childhood and adolescence remains incomplete. In the current meta-analysis, we synthesized the literature on (1) the contribution of genetic and environmental factors to NDDs, (2) the genetic and environmental overlap between different NDDs, and (3) the co-occurrence between NDDs and disruptive, impulse control and conduct disorders (DICCs). Searches were conducted across three platforms: Web of Science, Ovid Medline and Ovid Embase. Studies were included only if 75% or more of the sample consisted of children and/or adolescents and the studies had measured the aetiology of NDDs and DICCs using single-generation family designs or genomic methods. Studies that had selected participants on the basis of unrelated diagnoses or injuries were excluded. We performed multilevel, random-effects meta-analyses on 296 independent studies, including over four million (partly overlapping) individuals. We further explored developmental trajectories and the moderating roles of gender, measurement, geography and ancestry. We found all NDDs to be substantially heritable (family-based heritability, 0.66 (s.e. = 0.03); SNP heritability, 0.19 (s.e. = 0.03)). Meta-analytic genetic correlations between NDDs were moderate (grand family-based genetic correlation, 0.36 (s.e. = 0.12); grand SNP-based genetic correlation, 0.39 (s.e. = 0.19)) but differed substantially between pairs of disorders. The genetic overlap between NDDs and DICCs was strong (grand family-based genetic correlation, 0.62 (s.e. = 0.20)). While our work provides evidence to inform and potentially guide clinical and educational diagnostic procedures and practice, it also highlights the imbalance in the research effort that has characterized developmental genetics research.

Preferential looking to eyes versus mouth in early infancy: heritability and link to concurrent and later development.

BACKGROUND: From birth, infants orient preferentially to faces, and when looking at the face, they attend primarily to eyes and mouth. These areas convey different types of information, and earlier research suggests that genetic factors influence the preference for one or the other in young children. METHODS: In a sample of 535 5-month-old infant twins, we assessed eye (relative to mouth) preference in early infancy, i.e., before neural systems for social communication and language are fully developed. We investigated the contribution of genetic and environmental factors to the preference for looking at eyes, and the association with concurrent traits and follow-up measures. RESULTS: Eye preference was independent from all other concurrent traits measured, and had a moderate-to-high contribution from genetic influences (A = 0.57; 95% CI: 0.45, 0.66). Preference for eyes at 5 months was associated with higher parent ratings of receptive vocabulary at 14 months. No statistically significant association with later autistic traits was found. Preference for eyes was strikingly stable across different stimulus types (e.g., dynamic vs. still), suggesting that infants' preference at this age does not reflect sensitivity to low-level visual cues. CONCLUSIONS: These results suggest that individual differences in infants' preferential looking to eyes versus mouth to a substantial degree reflect genetic variation. The findings provide new leads on both the perceptual basis and the developmental consequences of these attentional biases.

Explaining the influence of non-shared environment (NSE) on symptoms of behaviour problems from preschool to adulthood: mind the missing NSE gap.

BACKGROUND: Individual differences in symptoms of behaviour problems in childhood and adolescence are not primarily due to nature or nurture - another substantial source of variance is non-shared environment (NSE). However, few specific environmental factors have been found to account for these NSE estimates. This creates a 'missing NSE' gap analogous to the 'missing heritability' gap, which refers to the shortfall in identifying DNA differences responsible for heritability. We assessed the extent to which variance in behaviour problem symptoms during the first two decades of life can be accounted for by measured NSE effects after controlling for genetics and shared environment. METHODS: The sample included 4,039 pairs of twins in the Twins Early Development Study whose environments and symptoms of behaviour problems were assessed in preschool, childhood, adolescence and early adulthood via parent, teacher and self-reports. Twin-specific environments were assessed via parent-reports, including early life adversity, parental feelings, parental discipline and classroom environment. Multivariate longitudinal twin model-fitting was employed to estimate the variance in behaviour problem symptoms at each age that could be predicted by environmental measures at the previous age. RESULTS: On average across childhood, adolescence and adulthood, parent-rated NSE composite measures accounted for 3.4% of the reliable NSE variance (1.0% of the total variance) in parent-rated, symptoms of behaviour problems, 0.5% (0.1%) in teacher-rated symptoms and 0.9% (0.5%) in self-rated symptoms after controlling for genetics, shared environment and error of measurement. Cumulatively across development, our parent-rated NSE measures in preschool, childhood and adolescence predicted 4.7% of the NSE variance (2.0% of the total variance) in parent-rated and 0.3% (0.2%) in self-rated behaviour problem symptoms in adulthood. CONCLUSIONS: The missing NSE gap between variance explained by measured environments and total NSE variance is large. Home and classroom environments are more likely to influence behaviour problem symptoms via genetics than via NSE.