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Background: Whether emotional problems during childhood and adolescence are longitudinally associated with adult alcohol use behaviors is unclear. This study examined associations between developmental trajectories of emotional problems and early adult alcohol use behaviors, while considering co-occurring conduct problems, developmental change/timing, sex differences, and potential confounds., Methods: Participants were from the Twins Early Development Study (analytic N = 19,908 individuals). Emotional and conduct problems were measured by parent reports at child ages 4, 7, and 9 years and via self-reports at ages 9, 11, and 16 years on the Strengths and Difficulties Questionnaire. Alcohol use behaviors (alcohol consumption and alcohol-related problems) were self-reported by the twins on the Alcohol Use Disorders Identification Test at age 22 years. Piecewise latent growth curve models described nonlinear developmental trajectories of emotional and conduct problems from ages 4 to 16. At age 22, alcohol use was regressed on emotional and conduct problems' intercepts and slopes from piecewise latent growth curve model and sex differences in regression coefficients were tested. Using twin modeling, Cholesky decompositions and direct path models were compared to test whether significant phenotypic associations were best explained by direct phenotypic influences or correlated genetic and environmental influences., Results: Emotional problems had different associations with alcohol-related problems versus alcohol consumption. After accounting for direct influences from conduct problems, emotional problems were not associated with alcohol-related problems, while emotional problems at age 9 were negatively associated with alcohol consumption in males., Conclusions: Overall, findings did not support emotional problems as prospective risk factors for severe alcohol use above and beyond risks associated with conduct problems. Sex- and age-specific links between emotional problems and alcohol consumption in early adulthood may be worthy of further exploration, particularly as twin analyses improved our confidence that such links may be underpinned by causal mechanisms., (© 2024 The Author(s). Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Background: Children and adolescents demonstrate diverse patterns of symptom change and disorder remission following cognitive behavioural therapy (CBT) for anxiety disorders. To better understand children who respond sub-optimally to CBT, this study investigated youths (N = 1,483) who continued to meet criteria for one or more clinical anxiety diagnosis immediately following treatment or at any point during the 12 months following treatment., Methods: Data were collected from 10 clinical sites with assessments at pre-and post-treatment and at least once more at 3, 6 or 12-month follow-up. Participants were assigned to one of three groups based on diagnostic status for youths who: (a) retained an anxiety diagnosis from post to end point (minimal responders); (b) remitted anxiety diagnoses at post but relapsed by end point (relapsed responders); and (c) retained a diagnosis at post but remitted to be diagnosis free at end point (delayed responders). Growth curve models assessed patterns of change over time for the three groups and examined predictors associated with these patterns including demographic, clinical and parental factors, as well as treatment factors., Results: Higher primary disorder severity, being older, having a greater number of anxiety disorders, having social anxiety disorder, as well as higher maternal psychopathology differentiated the minimal responders from the delayed and relapsed responders at the baseline. Results from the growth curve models showed that severity of the primary disorder and treatment modality differentiated patterns of linear change only. Higher severity was associated with significantly less improvement over time for the minimal and relapsed response groups, as was receiving group CBT, when compared to the delayed response group., Conclusions: Sub-optimal response patterns can be partially differentiated using variables assessed at pre-treatment. Increased understanding of different patterns of change following treatment may provide direction for clinical decision-making and for tailoring treatments to specific groups of clinically anxious youth. Future research may benefit from assessing progress during treatment to detect emerging response patterns earlier., (© 2024 The Author(s). Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Background: Emotional symptoms, such as anxiety and depressive symptoms, are common during adolescence, often persist over time, and can precede the emergence of severe anxiety and depressive disorders. Studies suggest that a vicious cycle of reciprocal influences between emotional symptoms and interpersonal difficulties may explain why some adolescents suffer from persisting emotional symptoms. However, the role of different types of interpersonal difficulties, such as social isolation and peer victimisation, in these reciprocal associations is still unclear. In addition, the lack of longitudinal twin studies conducted on emotional symptoms during adolescence means that the genetic and environmental contributions to these relationships during adolescence remain unknown., Methods: Participants (N = 15,869) from the Twins Early Development Study completed self-reports of emotional symptoms, social isolation and peer victimisation at 12, 16 and 21 years old. A phenotypic cross-lagged model examined reciprocal associations between variables over time, and a genetic extension of this model examined the aetiology of the relationships between variables at each timepoint., Results: First, emotional symptoms were reciprocally and independently associated with both social isolation and peer victimisation over time, indicating that different forms of interpersonal difficulties uniquely contributed to emotional symptoms during adolescence and vice versa. Second, early peer victimisation predicted later emotional symptoms via social isolation in mid-adolescence, indicating that social isolation may constitute an intermediate pathway through which peer victimisation predicts longer-term emotional symptoms. Finally, individual differences in emotional symptoms were mostly accounted for by non-shared environmental factors at each timepoint, and both gene-environment and individual-specific environmental mechanisms were involved in the relationships between emotional symptoms and interpersonal difficulties., Conclusions: Our study highlights the necessity to intervene early in adolescence to prevent the escalation of emotional symptoms over time and to consider social isolation and peer victimisation as important risk factors for the long-term persistence of emotional symptoms., (© 2023 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Diathesis-stress models conceptualise individual differences in propensity for psychopathology as an interaction between environmental risk factors and intra-individual vulnerabilities. In contrast, the differential susceptibility theory and related frameworks view intra-individual differences as variations in sensitivity to the environments rather than merely vulnerability to them. Specifically, they suggest that more sensitive individuals are more affected by the quality of their context, whether positive or negative, than others who are less sensitive. Empirical research over the last two decades has found support for this notion in that greater sensitivity is associated with a greater risk of psychopathology in adverse contexts, but also with lower risk in positive environments. However, despite growing academic and public interest in this field, it is currently unclear to what extent the differential susceptibility model is relevant, or applicable, to clinical practice. The purpose of this review is to focus on the differential susceptibility theory as an alternative explanation of individual differences in mental health and examine its relevance in the treatment of mental health problems in young people. We provide an overview of differential susceptibility and related theories, and current relevant research in the field. We identify potential implications of differential susceptibility models for understanding and treating mental health problems in young people, whilst also highlighting important gaps in research that limit their application at present. Finally, we suggest directions for future research that will assist in the translation of differential susceptibility theories into clinical practice., (© 2023 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

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., (© 2022 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Background: Despite being considered a measure of environmental risk, reported life events are partly heritable. One mechanism that may contribute to this heritability is genetic influences on sensitivity, relating to how individuals process and interpret internal and external signals. The aim of this study was to explore the genetic and environmental overlap between self-reported life events and measures of sensitivity., Methods: At age 17, 2,939 individuals from the Twins Early Development Study (TEDS) completed measures of anxiety sensitivity (Children's Anxiety Sensitivity Index), environmental sensitivity (Highly Sensitive Child Scale) and reported their experience of 20 recent life events. Using multivariate Cholesky decomposition models, we investigated the shared genetic and environmental influences on the associations between these measures of sensitivity and the number of reported life events, as well as both negative and positive ratings of life events., Results: The majority of the associations between anxiety sensitivity, environmental sensitivity and reported life events were explained by shared genetic influences (60%-75%), with the remainder explained by nonshared environmental influences (25%-40%). Environmental sensitivity showed comparable genetic correlations with both negative and positive ratings of life events (r A  = .21 and .15), anxiety sensitivity only showed a significant genetic correlation with negative ratings of life events (r A  = .33). Approximately 10% of the genetic influences on reported life events were accounted for by influences shared with anxiety sensitivity and environmental sensitivity., Conclusion: Differences in how individuals process the contextual aspects of the environment or interpret their own physical and emotional response to environmental stimuli may be one mechanism through which genetic liability influences the subjective experience of life events., (© 2022 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Background: One goal of the DNA revolution is to predict problems in order to prevent them. We tested here if the prediction of behaviour problems from genome-wide polygenic scores (GPS) can be improved by creating composites across ages and across raters and by using a multi-GPS approach that includes GPS for adult psychiatric disorders as well as for childhood behaviour problems., Method: Our sample included 3,065 genotyped unrelated individuals from the Twins Early Development Study who were assessed longitudinally for hyperactivity, conduct, emotional problems, and peer problems as rated by parents, teachers, and children themselves. GPS created from 15 genome-wide association studies were used separately and jointly to test the prediction of behaviour problems composites (general behaviour problems, externalising, and internalising) across ages (from age 2 to 21) and across raters in penalised regression models. Based on the regression weights, we created multi-trait GPS reflecting the best prediction of behaviour problems. We compared GPS prediction to twin heritability using the same sample and measures., Results: Multi-GPS prediction of behaviour problems increased from <2% of the variance for observed traits to up to 6% for cross-age and cross-rater composites. Twin study estimates of heritability, although to a lesser extent, mirrored patterns of multi-GPS prediction as they increased from <40% to 83%., Conclusions: The ability of GPS to predict behaviour problems can be improved by using multiple GPS, cross-age composites and cross-rater composites, although the effect sizes remain modest, up to 6%. Our approach can be used in any genotyped sample to create multi-trait GPS predictors of behaviour problems that will be more predictive than polygenic scores based on a single age, rater, or GPS., (© 2021 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Background: Parental criticism is correlated with internalising symptoms in adolescent offspring. This correlation could in part reflect their genetic relatedness, if the same genes influence behaviours in both parents and offspring. We use a Children-of-Twins design to assess whether parent-reported criticism and offspring internalising symptoms remain associated after controlling for shared genes. To aid interpretation of our results and those of previous Children-of-Twins studies, we examine statistical power for the detection of genetic effects and explore the direction of possible causal effects between generations., Methods: Data were drawn from two Swedish twin samples, comprising 876 adult twin pairs with adolescent offspring and 1,030 adolescent twin pairs with parents. Parent reports of criticism towards their offspring were collected concurrently with parent and offspring reports of adolescent internalising symptoms. Children-of-Twins structural equation models were used to control for genetic influence on the intergenerational association between parental criticism and adolescent internalising., Results: Parental criticism was associated with adolescent internalising symptoms after controlling for genetic influence. No significant role was found for shared genes influencing phenotypes in both generations, although power analyses suggested that some genetic effects may have gone undetected. Models could not distinguish directionality for nongenetic, causal effects between generations., Conclusions: Parental criticism may be involved in psychosocial family processes in the context of adolescent internalising. Future studies should seek to identify these processes and provide clarity on the direction of potential causal effects., (© 2021 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Background: Shame is considered a maladaptive self-conscious emotion that commonly co-occurs alongside depression and anxiety. Little is known, however, about the aetiology of shame and its associations with depression and anxiety. We estimated, for the first time, genetic and environmental influences on shame and on its associations with depression and anxiety in adolescence., Methods: The sample was twin and sibling pairs from the Genesis 1219 Study (Time 1, N = 2,685; males 42.8%, M age  = 14.95, SD = 1.67, age range: 12-21; Time 2, N = 1618; males 39.7%, M age  = 16.97, SD = 1.64, age range: 14-23). Participants completed validated questionnaires to measure shame (at Time 1), depression and anxiety (at Times 1 and 2)., Results: Shame was moderately to strongly associated with concurrent depression and anxiety. Prospectively, shame was significantly associated with an increase in depression, but not anxiety. Genetic analyses revealed that shame was moderately heritable with substantial nonshared environmental influence. The associations between shame and concurrent depression and anxiety were primarily accounted for by overlapping genetic influences. Prospectively, the association between shame and later depression was primarily accounted for by genetic and nonshared environmental influences shared with earlier depression. The unique association between shame and later depression was mostly explained by common nonshared environmental influences., Conclusions: The findings offer novel evidence regarding aetiology of shame-although moderately heritable, shame in adolescents may also result from nonshared environmental factors. Genetic and nonshared environmental influences contribute to the co-occurrence of shame with depression and anxiety., (© 2021 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Do associations between maternal anxiety symptoms and offspring mental health remain after comparing differentially exposed siblings? Participants were 17,724 offspring siblings and 11,553 mothers from the Norwegian Mother and Child Cohort study. Mothers reported anxiety and depressive symptoms at 30 weeks' gestation, and 0.5, 1.5, 3, and 5 years postpartum. Child internalizing and externalizing problems were assessed at ages 1.5, 3, and 5, and modeled using multilevel analyses with repeated measures nested within siblings, nested within mothers. Maternal pre- and postnatal anxiety were no longer associated with child internalizing or externalizing problems after adjusting for maternal depression and familial confounding. Maternal anxiety when the children were in preschool age, however, remained significantly associated with child internalizing but not externalizing problems., (© 2018 Society for Research in Child Development.)

Background: Diverse behaviour problems in childhood correlate phenotypically, suggesting a general dimension of psychopathology that has been called the p factor. The shared genetic architecture between childhood psychopathology traits also supports a genetic p. This study systematically investigates the manifestation of this common dimension across self-, parent- and teacher-rated measures in childhood and adolescence., Methods: The sample included 7,026 twin pairs from the Twins Early Development Study (TEDS). First, we employed multivariate twin models to estimate common genetic and environmental influences on p based on diverse measures of behaviour problems rated by children, parents and teachers at ages 7, 9, 12 and 16 (depressive traits, emotional problems, peer problems, autism traits, hyperactivity, antisocial behaviour, conduct problems and psychopathic tendencies). Second, to assess the stability of genetic and environmental influences on p across time, we conducted longitudinal twin modelling of the first phenotypic principal components of childhood psychopathological measures across each of the four ages. Third, we created a genetic p factor in 7,026 unrelated genotyped individuals based on eight polygenic scores for psychiatric disorders to estimate how a general polygenic predisposition to mostly adult psychiatric disorders relates to childhood p., Results: Behaviour problems were consistently correlated phenotypically and genetically across ages and raters. The p factor is substantially heritable (50%-60%) and manifests consistently across diverse ages and raters. However, residual variation in the common factor models indicates unique contributions as well. Genetic correlations of p components across childhood and adolescence suggest stability over time (49%-78%). A polygenic general psychopathology factor derived from studies of psychiatric disorders consistently predicted a general phenotypic p factor across development (0.3%-0.9%)., Conclusions: Diverse forms of psychopathology generally load on a common p factor, which is highly heritable. There are substantial genetic influences on the stability of p across childhood. Our analyses indicate genetic overlap between general risk for psychiatric disorders in adulthood and p in childhood, even as young as age 7. The p factor has far-reaching implications for genomic research and, eventually, for diagnosis and treatment of behaviour problems., (© 2019 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Background: Anxiety in parents is associated with anxiety in offspring, although little is known about the mechanisms underpinning these intergenerational associations. We conducted the first genetically sensitive study to simultaneously examine the effects of mother, father and child anxiety symptoms on each other over time., Method: Adoptive parent and child symptoms were measured at child ages 6, 7 and 8 years from 305 families involved in the Early Growth and Development Study, using a prospective adoption design. Children were adopted at birth to nonrelatives, and composite data on internalising problems within birth families were used as a proxy measure of offspring inherited risk for anxiety. Structural equation models were fitted to the data to examine prospective associations between adoptive mother, father and child symptoms, whilst accounting for individuals' symptom stability over time., Results: Child anxiety symptoms at age 7 predicted adoptive mothers' anxiety symptoms at age 8. No mother-to-child or child-to-father effects were observed. These results were consistent in sensitivity analyses using only paternal offspring reports and using a second measure of child anxiety symptoms. Fathers' anxiety symptoms at child age 6 prospectively predicted child symptoms, but only when paternal offspring reports were included in the model. Composite data on birth family internalising problems were not associated with child anxiety symptoms., Conclusions: Results show environmentally mediated associations between parent and child anxiety symptoms. Results support developmental theories suggesting that child anxiety symptoms can exert influence on caregivers, and mothers and fathers may play unique roles during the development of child symptoms. Further research is needed on the role of genetic transmission associated with anxiety symptoms in biologically related families. In the meantime, researchers and clinicians should strive to include fathers in assessments and consider the effects of child symptoms on caregivers., (© 2019 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Background: Several delivery formats of cognitive behaviour therapy (CBT) for child anxiety have been proposed, however, there is little consensus on the optimal delivery format. The primary goal of this study was to investigate the impact of the child's primary anxiety diagnosis on changes in clinical severity (of the primary problem) during individual CBT, group CBT and guided parent-led CBT. The secondary goal was to investigate the impact of the child's primary anxiety diagnosis on rates of remission for the three treatment formats., Methods: A sample of 1,253 children (5-12 years; Mage = 9.3, SD = 1.7) was pooled from CBT trials carried out at 10 sites. Children had a primary diagnosis of generalised anxiety disorder (GAD), social anxiety disorder (SoAD), specific phobia (SP) or separation anxiety disorder (SAD). Children and parents completed a semistructured clinical interview to assess the presence and severity of DSM-IV psychiatric disorders at preintervention, postintervention and follow-up. Linear mixture modelling was used to evaluate the primary research question and logistic modelling was used to investigate the secondary research question., Results: In children with primary GAD, SAD or SoAD, there were no significant differences between delivery formats. However, children with primary SP showed significantly larger reductions in clinical severity following individual CBT compared to group CBT and guided parent-led CBT. The results were mirrored in the analysis of remission responses with the exception that individual CBT was no longer superior to group CBT for children with a primary SP. The difference between individual and group was not significant when follow-up data were examined separately., Conclusions: Data show there may be greater clinical benefit by allocating children with a primary SP to individual CBT, although future research on cost-effectiveness is needed to determine whether the additional clinical benefits justify the additional resources required., (© 2018 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

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., (© 2017 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Background: Low self-worth during adolescence predicts a range of emotional and behavioural problems. As such, identifying potential sources of influence on self-worth is important. Aspects of the parent-child relationship are often associated with adolescent self-worth but to date it is unclear whether such associations may be attributable to familial confounding (e.g. genetic relatedness). We set out to clarify the nature of relationships between parental expressed affection and adolescent self-worth, and parent-child closeness and adolescent self-worth., Methods: We used data from the Twin and Offspring Study in Sweden, a children-of-twins sample comprising 909 adult twin pairs with adolescent children. Using these data we were able to apply structural equation models with which we could examine whether associations remained after accounting for genetic transmission., Results: Results demonstrated that parent-child closeness and parental-expressed affection were both phenotypically associated with adolescent self-worth. Associations could not be attributed to genetic relatedness between parent and child., Conclusions: Parent-child closeness and parental affection are associated with adolescent self-worth above and beyond effects attributable to genetic relatedness. Data were cross-sectional, so the direction of effects cannot be confirmed but findings support the notion that positive parent-child relationships increase adolescent self-worth., (© 2016 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

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., (© 2014 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Background: Within a therapeutic gene by environment (G × E) framework, we recently demonstrated that variation in the Serotonin Transporter Promoter Polymorphism; 5HTTLPR and marker rs6330 in Nerve Growth Factor gene; NGF is associated with poorer outcomes following cognitive behaviour therapy (CBT) for child anxiety disorders. The aim of this study was to explore one potential means of extending the translational reach of G × E data in a way that may be clinically informative. We describe a 'risk-index' approach combining genetic, demographic and clinical data and test its ability to predict diagnostic outcome following CBT in anxious children., Method: DNA and clinical data were collected from 384 children with a primary anxiety disorder undergoing CBT. We tested our risk model in five cross-validation training sets., Results: In predicting treatment outcome, six variables had a minimum mean beta value of 0.5:5HTTLPR, NGF rs6330, gender, primary anxiety severity, comorbid mood disorder and comorbid externalising disorder. A risk index (range 0-8) constructed from these variables had moderate a predictive ability (AUC = .62-.69) in this study. Children scoring high on this index (5-8) were approximately three times as likely to retain their primary anxiety disorder at follow-up as compared with those children scoring 2 or less., Conclusion: Significant genetic, demographic and clinical predictors of outcome following CBT for anxiety-disordered children were identified. Combining these predictors within a risk index could be used to identify which children are less likely to be diagnosis-free following CBT alone and require longer or enhanced treatment. The 'risk-index' approach represents one means of harnessing the translational potential of G × E data., (© 2013 The Authors. Journal of Child Psychology and Psychiatry © 2013 Association for Child and Adolescent Mental Health.)

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., (© 2012 The Authors. Journal of Child Psychology and Psychiatry © 2012 Association for Child and Adolescent Mental Health.)

Background: Despite theoretical and empirical support for an association between maternal control and child anxiety, few studies have examined the origins of this association. Furthermore, none use observer-ratings of maternal control within a genetically informative design. This study addressed three questions: 1) do children who experience maternal control report higher anxiety levels than those who do not?; 2) to what extent do genetic and environmental factors influence maternal control and child anxiety?; 3) to what extent do genetic and environmental factors influence the associations between child anxiety and maternal control?, Method: Five hundred and thirty 8-year-old children (from 265 twin pairs) and their mothers were observed participating in an 'etch-a-sketch' task from which maternal control was rated. Children rated their anxiety using the Screen for Child Anxiety Related Emotional Disorders., Results: Children who experienced maternal behaviour rated as 'extreme control' reported higher anxiety levels than those who did not. Maternal control was highly heritable (A = .63), high self-rated anxiety less so (h(2)(g) = .36). The overlap between high child anxiety and maternal control was primarily due to shared genetic factors., Conclusions: These results suggest that maternal control is likely to have been elicited by children with high levels of anxiety.

Background: To investigate the association between normative repetitive routines of childhood and paediatric obsessive compulsive symptom syndrome (OCSS) and the extent to which it is genetically mediated., Methods: In a two-phase design a community sample of 4,662 6-year-old twin-pairs were sampled and 854 pairs were assessed in the second phase for normative repetitive routines using the Childhood Routines Inventory (CRI) and for OCSS by maternal-informant diagnostic interview. The OCSS phenotype was defined using standard diagnostic criteria for obsessive compulsive disorder, though regardless of impairment., Results: In the bivariate model, correlation between the CRI defined phenotype and the OCSS phenotype was estimated to be .40 (95% CI .27-.50), and this correlation was attributable wholly to additive genetic effects. The bivariate model also provided estimates of heritability of the two phenotypes separately: 55% (95% CI 80-89%) for the OCSS phenotype, with the remaining variance attributable mainly to non-shared environment, and 50% (95% CI 39-62%) for CRI assessed normative repetitive routines of childhood, with 36% of the remaining variance attributable to shared environment and 14% to non-shared., Conclusions: The moderate correlation between normative childhood repetitive routines and obsessive compulsive symptomatology, attributable to genetic factors, is consistent with the hypothesis that high levels of this trait in young children constitute a risk factor for the development of obsessive compulsive symptoms.

Background: Antisocial behaviour is often comorbid with depressed mood but is itself a collection of heterogeneous behaviours. Using a genetically informative design, we examine heterogeneity in antisocial behaviour and overlaps between different forms of antisocial behaviour with depressed mood., Methods: Data were drawn from the G1219 large-scale community sample containing self-report questionnaire data from 941 twin pairs and 328 sibling-pairs aged 12-21 years., Results: Inter-correlations among oppositionality, physical aggression and delinquency, and between the antisocial subscales and depressed mood, were mediated by genetic and non-shared environmental influences. Genetic factors generally contributed more to the correlations than the non-shared environment., Conclusions: These results indicate that many genetic and non-shared environmental influences were common to all the traits studied, but there was also evidence for trait-specific effects.

Background: Genetic risks for depression may be expressed through greater exposure towards environmental stressors (gene-environment correlation, rGE) and increased susceptibility to these stressors (gene-environment interaction, G x E). While these effects are often studied independently, evidence supports their co-occurrence on depression., Methods: Adolescent twin and sibling data was used to assess correlations and interactions between genetic risks for depressive symptoms and two putative environmental stressors: dependent negative life events and maternal punitive discipline., Results: Moderate genetic effects influenced each environmental risk factor, consistent with rGE. Genetic effects on environmental risks also contributed to depressive outcomes, implying genetic correlations between measures. Genetic effects on depressive symptoms changed across levels of negative life events and maternal punitive discipline, consistent with G x E. Finally, G x E co-occurred with rGE on depressive outcomes., Conclusions: Adolescents at genetic risk for depressive phenotypes may be exposed to increased social adversity (rGE) and more susceptible to developing symptoms in response to these risks (G x E).

Background: Little is known about mechanisms of genetic influence on panic, particularly in childhood. Cognitive theories of panic disorder highlight threatening interpretations of physical sensations, and increased awareness of such sensations. Specifically, anxiety sensitivity (AS) and heartbeat perception (HBP) have been associated with panic in adults and children. We examined genetic and environmental influences on childhood AS, HBP, panic/somatic ratings, and their associations., Methods: Self-ratings of AS and DSM-based anxiety (including panic/somatic items) were obtained from 300 eight-year-old twin pairs (600 individuals), selected for mother-rated child anxiety at age 7. HBP was also assessed., Results: Panic/somatic ratings were significantly correlated with both AS (r = .55) and continuous HBP error scores (r = -.13). AS and HBP scores showed significantly greater correlations with panic/somatic ratings than with all other anxiety scales, except for HBP and school anxiety. Genetic influences on panic/somatic ratings were modest (15%), and moderate for both AS (37%), and HBP (30%). Non-shared environmental influences were substantial. The genetic correlations between panic/somatic ratings and both AS and HBP error scores were .98 (95% CI: .74-1.00) and -.46 (95% CI: -1.00-1.00) respectively., Conclusions: Self-ratings of panic and AS overlap genetically. Future research should consider whether AS mediates genetic risk for panic disorder.

This study examines frequency, overlap, and genetic and environmental influences on sleep difficulties, which are understudied in school-aged children. The Sleep Self Report and the Children's Sleep Habits Questionnaire were completed by 300 twin pairs (aged 8 years) and their parents. Child report suggested more frequent sleep problems than parent report (e.g., regular sleep onset delay was reported by 45% of children and 17% of parents). Associations between most of the sleep difficulties were small but significant (e.g., r(s)=.16 for parent report of bedtime resistance and sleep onset delay). Twin correlations based on parent reports suggest greater genetic influence (M=50%) than those based on child self-report (M=18%). Possible rater effects should be considered when evaluating children's sleep problems.

Background: Parenting factors may be important to the development of attributional style in adolescence, which in turn relates to depression symptoms. These relationships have mainly been considered in terms of social risk mechanisms, and little is known about the role of genetic influences., Method: Self-reported measures of attributional style, depression symptoms and parental disciplinary styles were administered to over 1300 adolescent twin and sibling pairs. Model-fitting techniques were used to examine the role of genetic and environmental influences., Results: Moderate genetic influences on attributional style were demonstrated, and furthermore, its association with depression reflected considerable genetic effects. Familial factors were implicated in the association between attributional style and punitive parenting, although genetic from shared environmental causes could not be distinguished., Conclusions: Our results demonstrate that attributional style is influenced by genetic, as well as social factors. Implications for aetiological pathways integrating cognitive, genetic and social factors on adolescent depression are discussed.

The monozygotic (MZ) twin differences method was used to examine nonshared environmental aspects of the association of parenting (punitive and constructive discipline), negative life events (independent and dependent), and peers (antisocial and prosocial) with adolescent depressive symptoms in terms of sequelae, risk, and maintaining factors. Two self-report booklets were completed by 328 MZ twin pairs aged 12-19 years, 6 months apart. Increased punitive discipline and negative life events were found to be relevant nonshared environmental factors that followed depression. Negative life events were the only factor that had a direct nonshared environmental association with concurrent depressive symptoms in adolescents independent of previous depressive symptoms, and all other study variables.

Background: This introductory guide presents the main two analytical approaches used by molecular geneticists: linkage and association., Methods: Traditional linkage and association methods are described, along with more recent advances in methodologies such as those using a variance components approach., Results: New methods are being developed all the time but the core principles of linkage and association remain the same. The basis of linkage is the transmission of a marker along with a disease within families, whereas association is based on the comparison of marker frequencies in case and control groups., Conclusions: It is becoming increasingly clear that effect sizes of individual markers on diseases and traits are likely to be very small. As such, much greater power is needed, and correspondingly greater sample sizes. Although non-replication is still a problem, molecular genetic studies in some areas such as attention deficit/hyperactivity disorder (ADHD) are starting to show greater convergence. Epidemiologists and other researchers with large well-characterized samples will be well placed to use these methods. Inter-disciplinary studies can then ask far more interesting questions such as those relating to developmental, multivariate and gene-environment interaction hypotheses.

Background: This special section on molecular genetics was invited in order to raise awareness of the potential of molecular genetic approaches to inform child psychologists, psychiatrists and related professionals. As much of the terminology is specific to the field, this introductory guide aims to aid readers who may be unfamiliar with the approaches of this discipline., Methods: Basic terminology and genetic processes are described, with sections covering 'The Human Genome' and 'Genetic Markers'., Results: The range of genetic markers is growing all the time, but those that are thought to be functional and/or are highly variable are particularly useful., Conclusions: Genotyping approaches that offer high efficiency, thus allowing for large numbers of genotypes on large numbers of individuals, are likely to come to the fore in the next few years.

Background: From middle childhood onwards, substantial evidence points to phenotypic differentiation between anxiety diagnostic categories such as generalised anxiety, separation anxiety, specific phobia, and obsessive-compulsive disorders. However, little is known about the genetics of these categories and especially about the phenotypic and genetic structure of related behaviours in pre-school children., Methods: We examined the phenotypic differentiation and genetics of mother-reported anxiety-related behaviours in 4,564 four-year-old twin pairs, from a population-based sample., Results: Confirmatory factor analyses provided support for five correlated factors: General Distress, Separation Anxiety, Fears, Obsessive-Compulsive Behaviours, and Shyness/Inhibition. Genetic influences were found on all five factors, but the pattern of influences differed considerably across them, with particularly high heritability estimates for Obsessive-Compulsive Behaviours and Shyness/Inhibition, and substantial shared environmental influence on Separation Anxiety. Multivariate genetic analyses revealed moderate genetic correlations between the five factors. Genetic overlap was particularly pronounced between General Distress and the other anxiety-related behaviours, accounting for about half of their covariance. Genetic variance on Obsessive-Compulsive Behaviours was the least correlated with the other scales. The shared environmental influences correlated highly across the factors, accounting for the greatest proportion of covariation between Separation Anxiety, Fears and Obsessive-Compulsive Behaviours. The non-shared environment influences were largely variable specific., Conclusions: These data provide evidence for phenotypic and genetic overlap as well as differentiation between aspects of anxiety-related behaviours in young children. We conclude that research with young children will benefit from more specific assessments of anxiety-related behaviours in addition to less differentiated assessments of 'internalising' symptoms.

Background: We investigated associations between behaviour problems and verbal and nonverbal cognitive abilities at 2, 3 and 4 years of age both for the entire distribution and for the lowest 5% and 10% of the verbal and nonverbal cognitive disabilities., Methods: A community sample of 4,000 pairs of twins born in England and Wales in 1994 and 1995 was assessed by their parents at 2, 3 and 4 years using the Revised Rutter Parent Scale for Preschool Children (RRPSPC, behaviour problems), the MacArthur Communicative Development Inventory (MCDI, verbal development), and the Parent Report of Children's Abilities (PARCA, nonverbal cognitive development)., Results: For the entire sample, behaviour problem scores were modestly associated with lower MCDI and PARCA scores - correlations were less than .30. Similarly modest effect sizes were found for relationships between behaviour problem scores and the lowest 5% and 10% of the MCDI and of the PARCA distributions. Associations were stronger for nonverbal than for verbal development, increased from 2 to 3 to 4 years, and, at the extremes of the distributions, were stronger for boys than for girls. Multivariate genetic analyses indicated that both genetic and shared environmental factors mediate the links between behaviour problems and cognitive development both for the total distribution and for the extremes. Genetic links may be stronger for the extremes than for the total sample., Conclusions: We conclude that, in this community sample of young children, associations between behaviour problems and verbal and nonverbal cognitive development are generally modest for the entire distribution and are no greater at the extremes than expected on the basis of the associations for the entire distribution.