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Sleep disturbances are common in attention deficit hyperactivity disorder (ADHD) and associated with poor outcomes. We tested whether, in children with ADHD, (1) polygenic liability for sleep phenotypes is over- or under-transmitted from parents, (2) this liability is linked to comorbid sleep disturbances, and (3) ADHD genetic risk is associated with comorbid sleep disturbances. We derived polygenic scores (PGS) for insomnia, chronotype, sleep duration, and ADHD, in 758 children (5–18 years old) diagnosed with ADHD and their parents. We conducted polygenic transmission disequilibrium tests for each sleep PGS in complete parent–offspring ADHD trios (N = 328) and an independent replication sample of ADHD trios (N = 844). Next, we tested whether insomnia, sleep duration, and ADHD PGS were associated with co-occurring sleep phenotypes (hypersomnia, insomnia, restless sleep, poor sleep quality, and nightmares) in children with ADHD. Children's insomnia and chronotype PGS did not differ from mid-parent average PGS but long sleep duration PGS were significantly over-transmitted to children with ADHD. This was supported by a combined analysis using the replication sample. Insomnia, sleep duration, and ADHD PGS were not associated with comorbid sleep disturbances. There is weak evidence that children with ADHD over-inherit polygenic liability for longer sleep duration and do not differentially inherit polygenic liability for insomnia or chronotype. There was insufficient evidence that childhood sleep disturbances were driven by polygenic liability for ADHD or sleep traits, suggesting that sleep disturbances in ADHD may be aetiologically different to general population sleep phenotypes and do not index greater ADHD genetic risk burden. [ABSTRACT FROM AUTHOR]

Peter McGuffin, a renowned researcher in the fields of behavioral and psychiatric genetics, passed away at the age of 74. He was known for his pioneering work in genetic approaches to studying clinical and behavioral phenotypes, utilizing family and twin designs as well as molecular genetic studies. McGuffin made significant contributions to gene discovery for major psychiatric disorders and played a crucial role in bringing genetics groups together to boost statistical power. He was also a respected clinician and mentor, inspiring many early career researchers in psychiatric genetics. McGuffin published over 500 scientific papers, received numerous accolades and awards, and had diverse talents and interests outside of academia. [Extracted from the article]

In the last 40 years, there has been a huge increase in autism genetics research and a rapidly growing number of discoveries. We now know autism is one of the most highly heritable disorders with negligible shared environmental contributions. Recent discoveries also show that rare variants of large effect size as well as small effect common gene variants all contribute to autism risk. These discoveries challenge traditional diagnostic boundaries and highlight huge heterogeneity in autism. In this review, we consider some of the key findings that are shaping current understanding of autism and what these discoveries mean for clinicians. [ABSTRACT FROM AUTHOR]

Attention deficit/hyperactivity disorder (ADHD) is associated with friendship difficulties. This may partly account for the increasingly recognised association between ADHD and subsequent depression. Little is known about the types of friendship difficulties that could contribute to the association between ADHD and depressive symptoms and whether other relationships, such as parent–child relationships, can mitigate against potential adverse effects of friendship difficulties. In a representative UK school sample (n = 1712), three main features of friendship (presence of friends, friendship quality and characteristics of the individual's classroom friendship group) were assessed in a longitudinal study with two assessment waves (W1, W2) during the first year of secondary school (children aged 11-12 years). These friendship features (W1) were investigated as potential mediators of the prospective association between teacher-rated ADHD symptoms (W1) and self-rated depressive symptoms (W2) seven months later. Parent–child relationship quality (W1) was tested as a moderator of any indirect effects of ADHD on depression via friendship. ADHD symptoms were inversely associated with friendship presence, friendship quality and positive characteristics of classroom friendship groups. Depressive symptoms were inversely associated with presence and quality of friendships. Friendship quality had indirect effects in the association between ADHD and subsequent depressive symptoms. There was some evidence of moderated mediation, whereby indirect effects via friendship quality attenuated slightly as children reported warmer parent–child relationships. This highlights the importance of considering the quality of friendships and parent–child relationships in children with ADHD symptoms. Fostering good quality relationships may help disrupt the link between ADHD symptomology and subsequent depression risk. [ABSTRACT FROM AUTHOR]

Attention deficit/hyperactivity disorder (ADHD) demonstrates a high level of comorbidity with major depressive disorder (MDD). One possible contributor to this is that the two disorders show high genetic correlation. However, the specific regions of the genome that may be responsible for this overlap are unclear. To identify variants associated with both ADHD and MDD, we performed a meta-analysis of GWAS of ADHD and MDD. All genome wide significant (p < 5 × 10–8) SNPs in the meta-analysis that were also strongly associated (p < 5 × 10–4) independently with each disorder were followed up. These putatively pleiotropic SNPs were tested for additional associations across a broad range of phenotypes. Fourteen linkage disequilibrium-independent SNPs were associated with each disorder separately (p < 5 × 10–4) and in the cross-disorder meta-analysis (p < 5 × 10–8). Nine of these SNPs had not been highlighted previously in either individual GWAS. Evidence supported nine of the fourteen SNPs acting as eQTL and two as brain eQTL. Index SNPs and their genomic regions demonstrated associations with other mental health phenotypes. Through conducting meta-analysis on ADHD and MDD only, our results build upon the previously observed genetic correlation between ADHD and MDD and reveal novel genomic regions that may be implicated in this overlap. [ABSTRACT FROM AUTHOR]

There is increasing evidence that childhood Attention-Deficit Hyperactivity Disorder (ADHD) elevates risk of later depression, but the mechanisms behind this association are unclear. We investigated the relationship between childhood ADHD symptoms and late-adolescent depressive symptoms in a population cohort, and examined whether academic attainment and peer problems mediated this association. ALSPAC (Avon Longitudinal Study of Parents and Children) is an ongoing prospective longitudinal population-based UK cohort that has collected data since September 1990. 2950 individuals with data on parent-reported ADHD symptoms in childhood (7.5 years) and self-reported depressive symptoms in late adolescence (17.5 years) were included in analyses. 2161 individuals with additional data at age 16 years on parent-reported peer problems as an indicator of peer relationships and formal examination results (General Certificate of Secondary Education; GCSE) as an indicator of academic attainment were included in mediation analyses. Childhood ADHD symptoms were associated with higher depressive symptoms (b = 0.49, SE = 0.11, p < 0.001) and an increased odds of clinically significant depressive symptoms in adolescence (OR = 1.27, 95% CI 1.15–1.41, p < 0.001). The association with depressive symptoms was mediated in part by peer problems and academic attainment which accounted for 14.68% and 20.13% of the total effect, respectively. Childhood ADHD is associated with increased risk of later depression. The relationship is mediated in part by peer relationships and academic attainment. This highlights peer relationships and academic attainment as potential targets of depression prevention and intervention in those with ADHD. Future research should investigate which aspects of peer relationships are important in conferring later risk for depression. [ABSTRACT FROM AUTHOR]

Although genetic factors may contribute to initial liability for ADHD onset, there is growing evidence of the potential importance of the rearing environment on the developmental course of ADHD symptomatology. However, associations between family-level variables (maternal hostility, maternal depressive symptoms) and child behaviors (developmental course of ADHD and aggression) may be explained by genes that are shared by biologically related parents and children. Furthermore, ADHD symptoms and aggression commonly co-occur: it is important to consider both simultaneously to have a better understanding of processes underlying the developmental course of ADHD and aggression. To addresses these issues, we employed a longitudinal genetically sensitive parent–offspring adoption design. Analyses were conducted using Cohort I (n = 340) of the Early Growth and Development Study with cross-validation analyses conducted with Cohort II (n = 178). Adoptive mother hostility, but not depression, was associated with later child ADHD symptoms and aggression. Mothers and their adopted children were genetically unrelated, removing passive rGE as a possible explanation. Early child impulsivity/activation was associated with later ADHD symptoms and aggression. Child impulsivity/activation was also associated with maternal hostility, with some evidence for evocative gene-environment correlation processes on adoptive mother depressive symptoms. This study provides novel insights into family-based environmental influences on child ADHD and aggression symptoms, independent of shared parental genetic factors, implications of which are further explicated in the discussion. [ABSTRACT FROM AUTHOR]

Psychiatric disorders show phenotypic as well as genetic overlaps. There are however also marked developmental changes throughout childhood. We investigated the extent to which, for a full range of early childhood psychopathology, a general "p" factor was explained by genetic liability, as indexed by multiple different psychiatric polygenic risk scores (PRS) and whether these relationships altered with age. The sample was a UK, prospective, population-based cohort with psychopathology data at age 7 (N = 8161) and age 13 (N = 7017). PRS were generated from large published genome-wide association studies. At both ages, we found evidence for a childhood "p" factor as well as for specific factors. Schizophrenia and attention-deficit/hyperactivity disorder (ADHD) PRS were associated with this general "p" factor at both ages but depression and autism spectrum disorder (ASD) PRS were not. We also found some evidence of associations between schizophrenia, ADHD and depression PRS with specific factors, but these were less robust and there was evidence for developmental changes. [ABSTRACT FROM AUTHOR]

Purpose: Specific child neurodevelopmental (ND) disorders such as ADHD and learning problems are associated with concurrent and future (up to early adulthood) mood problems. However, it is unclear whether findings generalise to population traits as well as diagnoses, to general as well as specific neurodevelopmental domains, and whether risk associations extend to later adulthood or diminish with age.Methods: We used data from a UK cohort of children born in 1958, the National Child Development Study (NCDS). ND problems were assessed at ages 7 and 11 years with parent- and teacher ratings of restlessness, hyperactivity and motor co-ordination difficulties, and by individual tests of reading, arithmetic and general cognitive ability. Mood (depression/anxiety) problems were assessed using the Malaise symptom screen at 23, 33, 42, and 50 years. Factor analyses were conducted to assess whether the specific neurodevelopmental domains could be aggregated into a general "ND" latent factor as well as specific factors. Associations with mood outcomes were then tested.Results: A bi-factor model with a general "ND" latent factor and specific "motor" and "cognition" factors fits the data well. The specific cognition and motor factor scores were associated with mood problems in early adulthood only. The "ND" factor demonstrated associations with mood problems at each adult follow-up (men - age 23 years: β = 0.17; age 33: β = 0.16; age 42: β = 0.14; age 50: β = 0.16; women - 23 years: β = 0.25; 33 years: β = 0.26; 42 years: β = 0.14; 50 years: β = 0.16; all ps < 0.01). Interactions by sex indicated that the association between this general factor and mood problems was more pronounced for women than men at ages 23 years (β = 0.09, p = 0.005) and 33 years (β = 0.10, p = 0.003), but not at 42 or 50 years (ps > 0.8).Conclusions: Our results suggest that, in a population-based cohort, a general, childhood neurodevelopmental difficulty factor is stably associated with mood problems in adult life. [ABSTRACT FROM AUTHOR]

Attention-deficit/hyperactivity disorder (ADHD) and depression commonly co-occur. Identifying children with ADHD at risk for later depression may allow early intervention and prevention. Irritability is one possible mechanism linking these two disorders. It is common in ADHD and associated with later depression in the general population. Cross-sectional studies suggest an association between irritability and depression in ADHD, but longitudinal research is limited. This study followed up a clinical ADHD sample longitudinally to examine: (1) the association between childhood irritability and later depression symptoms, and (2) whether irritability persistence is important in this association. At baseline, parents (n = 696) completed semi-structured interviews about their child (mean age = 10.9), providing information on child psychopathology, including irritability. A subsample (n = 249) was followed up after a mean of 5.4 years. Parent-completed Mood and Feelings Questionnaires provided information on depressive symptoms at follow-up. Parent-rated structured diagnostic interviews provided information on ADHD diagnosis and irritability at follow-up. Regression analyses examined associations between (i) baseline irritability and depression symptoms at follow-up, and (ii) persistent (vs. remitted) irritability and depression symptoms at follow-up. Analyses controlled for age, gender, depression symptoms, anxiety, ADHD symptoms, and ADHD medication at baseline. Baseline irritability was associated with depression symptoms at follow-up, but the association attenuated after controlling for anxiety and ADHD symptoms. Persistent irritability was associated with depression symptoms at follow-up, after including all covariates. Children with ADHD with persistent irritability are at elevated risk of developing depression symptoms. They may be a target for early intervention and prevention of depression. [ABSTRACT FROM AUTHOR]

Previous cross-sectional research has shown that parents of children with attention deficit hyperactivity disorder (ADHD) have high rates of psychopathology, especially ADHD and depression. However, it is not clear whether different types of parent psychopathology contribute to the course and persistence of ADHD in the child over time. The aim of this two wave study was to investigate if mother self-reported ADHD and depression influence persistence of offspring ADHD and conduct disorder symptom severity in adolescents diagnosed with ADHD in childhood. A sample of 143 males with a confirmed diagnosis of ADHD participated in this study. ADHD and conduct disorder symptoms were assessed at baseline and reassessed 4 years later. The boys in this sample had a mean age of 10.7 years at Time 1 (SD 2.14, range 6-15 years) and 13.73 years at Time 2 (SD 1.74, range 10-17 years). Questionnaire measures were used to assess ADHD and depression symptoms in mothers at Time 1. Mother self-reported ADHD was not associated with a change in child ADHD or conduct symptom severity over time. Mother self-reported depression was found to predict an increase in child conduct disorder symptoms, but did not contribute to ADHD symptom levels. This study provides the first evidence that concurrent depression in mothers may be a predictor of worsening conduct disorder symptoms in adolescents with ADHD. It may, therefore, be important to screen for depression in mothers of children with ADHD in clinical practice to tailor interventions accordingly. [ABSTRACT FROM AUTHOR]

Purpose: Childhood hyperactivity leads to mental health problems, but it is not known whether there are long-term risks for adult mood problems in unselected population cohorts that extend to mid-life. Aims were to examine links between childhood hyperactivity and mood problems up to age 50 years and to consider confounding factors and gender differences in associations.Methods: The National Child Development Study (NCDS) is a UK cohort of children born in 1958. Children with (N = 453) and without (N = 9192) pervasive and persistent hyperactivity were followed to age 50. Adult mood was assessed using the Malaise Inventory at ages 23, 33, 42, and 50 years and the CIS-R interview at 45 years.Results: Childhood hyperactivity predicted low mood at all adult assessments (ES = 0.27-0.45), including after covariate adjustment (childhood adversity, emotional and behavioural problems, and attainment).Conclusion: Hyperactivity has enduring risk effects on low mood throughout the life course that extend to middle age. [ABSTRACT FROM AUTHOR]

There is a renewed interest in better conceptualizing trajectories of attention-deficit/hyperactivity disorder (ADHD) from childhood to adulthood, driven by an increased recognition of long-term impairment and potential persistence beyond childhood and adolescence. This review addresses the following major issues relevant to the course of ADHD in light of current evidence from longitudinal studies: (1) conceptual and methodological issues related to measurement of persistence of ADHD, (2) estimates of persistence rate from childhood to adulthood and its predictors, (3) long-term negative outcomes of childhood ADHD and their early predictors, and (4) the recently proposed new adult-onset ADHD. Estimates of persistence vary widely in the literature, and diagnostic criteria, sample characteristics, and information source are the most important factors explaining variability among studies. Evidence indicates that ADHD severity, comorbid conduct disorder and major depressive disorder, and treatment for ADHD are the main predictors of ADHD persistence from childhood to adulthood. Comorbid conduct disorder and ADHD severity in childhood are the most important predictors of adverse outcomes in adulthood among children with ADHD. Three recent population studies suggested the existence of a significant proportion of individuals who report onset of ADHD symptoms and impairments after childhood. Finally, we highlight areas for improvement to increase our understanding of ADHD across the life span. [ABSTRACT FROM AUTHOR]

Traits of autism spectrum disorder (ASD) in children with attention-deficit/hyperactivity disorder (ADHD) have previously been found to index clinical severity. This study examined the association of ASD traits with diffusion parameters in adolescent males with ADHD (n = 17), and also compared WM microstructure relative to controls (n = 17). Significant associations ( p < 0.05, corrected) were found between fractional anisotropy/radial diffusivity and ASD trait severity (positive and negative correlations respectively), mostly in the right posterior limb of the internal capsule/corticospinal tract, right cerebellar peduncle and the midbrain. No case-control differences were found for the diffusion parameters investigated. This is the first report of a WM microstructural signature of autistic traits in ADHD. Thus, even in the absence of full disorder, ASD traits may index a distinctive underlying neurobiology in ADHD. [ABSTRACT FROM AUTHOR]

Identifying environmental risk factors in the pathway to depression is an important research goal. To extend prior research, designs that rule out alternative explanatory factors; genetic effects and reverse causation, and permit tests of both parent and child gender are required. The present study used two different samples to address these issues. A longitudinal community sample of 316 families (157 boys, 159 girls) aged 11-12 years (mean 11.7) at Time 1 and 12-13 years at Time 2 (mean 12.7) was used to test the direction of effects between parent hostility and child and adolescent depression symptoms. A genetically sensitive sample of 1,075 twin pairs; 653 dizygotic (135 male, 183 female, 335 opposite sex) and 422 monozygotic (180 male and 242 female) aged 12-20 years (mean 16.12) was used to test whether parent hostility had environmental effects. Analyses were conducted separately by parent and child gender. Using cross-lagged panel analyses, the association between mother-daughter hostility and depression symptoms was found to be longitudinal and bidirectional with reciprocal effects between mothers and daughters. Behavioural genetic analyses in the twin sample revealed a significant environmental link between mother hostility and symptoms of daughter depression independent of genetic factors. A significant pathway was found between daughter depressive symptoms and father hostility but not vice versa. This association was accounted for by genetic factors in behavioural genetic analyses. Findings provide evidence of an environmental risk pathway to depression symptoms and identify patterns of variation according to parent and child gender. Results are discussed in relation to underlying explanatory processes and clinical implications. [ABSTRACT FROM AUTHOR]

Traits of autistic spectrum disorders (ASD) occur frequently in attention deficit hyperactivity disorder (ADHD), but the significance of their presence in terms of phenotype and underlying neurobiology is not properly understood. This analysis aimed to determine whether higher levels of autistic traits, as measured by the Social Communication Questionnaire (SCQ), index a more severe presentation in a large, rigorously phenotyped sample of children with ADHD ( N = 711). Regression analyses were used to examine association of SCQ scores with core ADHD features, clinical comorbidities and cognitive and developmental features, with adjustment for putative confounders. For outcomes showing association with total SCQ score, secondary analyses determined levels of differential association of the three ASD sub-domains. Results suggest that increasing ASD symptomatology within ADHD is associated with a more severe phenotype in terms of oppositional, conduct and anxiety symptoms, lower full-scale IQ, working memory deficits and general motor problems. These associations persisted after accounting for ADHD severity, suggesting that autistic symptomatology independently indexes the severity of comorbid impairments in the context of ADHD. Sub-domain scores did not show unique contributions to most outcomes, except that social deficits were independently associated with oppositional symptoms and repetitive behaviours independently predicted hyperactive-impulsive symptoms and motor problems. It would be worthwhile for clinicians to consider levels of socio-communicative and repetitive traits in those with ADHD who do not meet diagnostic criteria for ASD, as they index higher levels of phenotypic complexity, which may have implications for efficacy of interventions. [ABSTRACT FROM AUTHOR]

Attention-deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) often co-occur. Factor analyses of ASD traits in children with and without ASD indicate the presence of social and restrictive-repetitive behaviour (RRB) factors. This study used exploratory factor analyses to determine the structure of ASD traits (assessed using the Social Communication Questionnaire) in children with ADHD. Distinct factors were observed for 'social' and 'rigidity' traits, corresponding to previous factor analyses in clinical ASD and population samples. This indicates that the split between social-communicative and RRB dimensions is unaffected by ADHD in children. Moreover, the study also finds that there is some overlap across hyperactive-impulsive symptoms and RRB traits in children with ADHD, which merits further investigation. [ABSTRACT FROM AUTHOR]

An enduring tendency towards negative thinking is thought to increase vulnerability for future depression. However, it has not been possible to assess this tendency in non-depressed mood states. We examined if response latency to endorse dysfunctional attitudes is associated with depressive outcomes in a longitudinal study. A sample of young people at familial risk of depression ( N = 252, aged 10-19, 56.3 % female) completed a computer-administered dysfunctional attitude scale. The main outcome measure was the difference in reaction time to agree versus disagree with dysfunctional attitudes. Cross-sectional differences between current and previous depression and no psychiatric disorder groups as well as longitudinal associations with depressive symptoms were examined. Young people with current and previous depression were quicker to agree with dysfunctional attitudes than those without disorder. In young people free from depressive disorder, faster agreements with dysfunctional attitudes were specifically associated with increased depressive symptoms over time. Self-reported dysfunctional attitudes did not differentiate the formerly depressed and no disorder groups and showed a longitudinal association with depressive symptoms for older adolescents only. Reaction time to endorse dysfunctional attitudes may indicate changes in affective processing that represent an early risk for future depression that is not indexed by self-report measures of negative thought. [ABSTRACT FROM AUTHOR]

Most psychiatric disorders are moderately to highly heritable. The degree to which genetic variation is unique to individual disorders or shared across disorders is unclear. To examine shared genetic etiology, we use genome-wide genotype data from the Psychiatric Genomics Consortium (PGC) for cases and controls in schizophrenia, bipolar disorder, major depressive disorder, autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD). We apply univariate and bivariate methods for the estimation of genetic variation within and covariation between disorders. SNPs explained 17-29% of the variance in liability. The genetic correlation calculated using common SNPs was high between schizophrenia and bipolar disorder (0.68 ± 0.04 s.e.), moderate between schizophrenia and major depressive disorder (0.43 ± 0.06 s.e.), bipolar disorder and major depressive disorder (0.47 ± 0.06 s.e.), and ADHD and major depressive disorder (0.32 ± 0.07 s.e.), low between schizophrenia and ASD (0.16 ± 0.06 s.e.) and non-significant for other pairs of disorders as well as between psychiatric disorders and the negative control of Crohn's disease. This empirical evidence of shared genetic etiology for psychiatric disorders can inform nosology and encourages the investigation of common pathophysiologies for related disorders. [ABSTRACT FROM AUTHOR]

Although Attention Deficit Hyperactivity Disorder (ADHD) is recognised to be a familial and heritable disorder, little is known about the broader family characteristics of having a parent with ADHD problems. The main aim of this study was to investigate the relationship between parent ADHD problems, child clinical presentation and family functioning in a sample of children with ADHD. The sample consisted of 570 children with ADHD. Child psychopathology was assessed using a semi-structured diagnostic interview. Questionnaires were used to assess ADHD in the parents (childhood and current symptoms), family environment and mother/father-child relationship. Parental ADHD problems were associated with a range of adverse clinical outcomes in children with no difference in effects for mothers with ADHD problems compared to fathers with ADHD problems. Levels of maternal hostility were higher in families where mothers had ADHD problems, but reduced where fathers had ADHD problems. Parental ADHD problems index higher risk for more severe clinical presentation of ADHD in children and higher levels of family conflict (where there are maternal but not paternal ADHD problems). This study highlights that children with more severe behavioural symptoms are more likely to have a parent with persistent ADHD which has important implications when considering treatment and intervention strategies. [ABSTRACT FROM AUTHOR]

Purpose: Attention-deficit hyperactivity disorder (ADHD) is associated with increased use of health, social and education services. There is a lack of data to quantify the economic burden of ADHD in the UK. The aim of this study was to estimate additional education, health and social care costs amongst adolescents in the UK diagnosed with ADHD. Methods: Participants were 143, 12- to 18-year-olds from the Cardiff longitudinal ADHD study. Service use relating to mental health over the previous year was measured using the children's service interview. Individual resource use was combined with unit cost data, from national sources, to calculate costs per patient and subsequently the mean cost per patient. Mean costs, 95 % confidence intervals and median use were calculated using nonparametric bootstrapping methods. Results: The mean cost per adolescent for NHS, social care and education resources used in a 12-month period related to ADHD was £5,493 (£4,415.68, £6,678.61) in 2010 prices and the median was £2,327. Education and NHS resources accounted for approximately 76 and 24 %, respectively. Estimated annual total UK costs are £670 million. Conclusions: The additional costs to the NHS and education system of treating adolescents remain substantial for several years after the initial ADHD diagnosis. There exists a need to develop and evaluate early interventions which have the potential to reduce the longer-term burden, particularly on education resource use. [ABSTRACT FROM AUTHOR]

This study investigated moderation of the association between recurrent maternal depression and offspring depression symptoms by a selection of biologically relevant gene variants. 271 children/adolescents (aged 9.00 to 16.00 years) whose mothers had experienced at least two episodes of DSM-IV major depression and 165 controls (aged 12.25 to 16.67 years) drawn from a population-based twin register were used. Seven single nucleotide polymorphisms (SNPs) from three genes were genotyped in children. The genes were the Corticotropin Receptor Type 1 gene ( CRHR1), the gene coding for the FK506 binding protein 5 ( FKBP5) and the Glucocorticoid receptor gene ( NR3c1) along with a haplotype formed by the SNPs in CRHR1. A significant association was found between recurrent maternal depression and depression symptoms in offspring. None of the SNPs were associated with offspring depression symptoms and associations did not differ according to the presence of recurrent maternal depression. However, caution is required due to a relatively small sample size. [ABSTRACT FROM AUTHOR]

A number of public health interventions aimed at increasing the uptake of breastfeeding are in place in the United States and other Western countries. While the physical health and nutritional benefits of breastfeeding for the mother and child are relatively well established, the evidence for psychological effects is less clear. This study aimed to examine whether there is an association between breastfeeding and later conduct problems in children. It also considered the extent to which any relationship is attributable to maternally-provided inherited characteristics that influence both likelihood of breastfeeding and child conduct problems. A prenatal cross-fostering design with a sample of 870 families with a child aged 4-11 years was used. Mothers were genetically related or unrelated to their child as a result of assisted reproductive technologies. The relationship between breastfeeding and conduct problems was assessed while controlling for theorised measured confounders by multivariate regression (e.g. maternal smoking, education, and antisocial behaviour), and for unmeasured inherited factors by testing associations separately for related and unrelated mother-child pairs. Breastfeeding was associated with lower levels of conduct disorder symptoms in offspring in middle childhood. Breastfeeding was associated with lower levels of conduct problems even after controlling for observed confounders in the genetically related group, but not in the genetically unrelated group. In contrast, maternal antisocial behaviour showed robust associations with child conduct problems after controlling for measured and inherited confounders. These findings highlight the importance of using genetically sensitive designs in order to test causal environmental influences. [ABSTRACT FROM AUTHOR]

The developmental trajectory of attention-deficit hyperactivity disorder (ADHD) is variable. Utilizing a longitudinally assessed sample, we investigated the contribution of susceptibility gene variants, previously implicated through pooled or meta-analyses, to the developmental course of Attention-Deficit Hyperactivity Disorder over time. 151 children (aged 6–12) who met diagnostic criteria for ADHD were assessed using research diagnostic interviews during childhood and 5 years later in adolescence. Severity was defined as total number of ADHD symptoms at baseline and reassessment. Association with variants at DRD4, DRD5, and the dopamine transporter gene, DAT was analyzed using linear regression. As expected, affected individuals showed a decline in ADHD severity over time. The DRD4 48 bp VNTR 7-repeat and DRD5 CA(n) microsatellite marker 148 bp risk alleles were associated with persistent ADHD. Those possessing the DRD4 7 repeat risk allele showed less of a decline in severity at reassessment than those without the risk allele. Those carrying the DRD4 7 risk allele showed greater symptom severity at follow-up and less ADHD reduction over time. These findings support the hypothesis that some susceptibility genes for ADHD also influence its developmental course. [ABSTRACT FROM AUTHOR]

This study investigated genetic and environmental influences on the associations between mother–child relationship quality (warmth and hostility) and adolescent conduct problems and cigarette use. Participants included 601 mothers and adolescent twin pairs (aged 12–17 years). Mothers and adolescents provided separate reports of mother-to-child warmth and hostility. A combined measure of mother and adolescent reported conduct problems was used while adolescents provided reports of their cigarette use. Analyses were conducted using bivariate genetic analyses of correlated factors models and regression analyses of monozygotic twin differences. Genetic influences were found for most ratings of the parent–child relationship, with evidence of gender and/or rater-specificity for some measures. The relationship between mother–child hostility with adolescent conduct problems and cigarette use was influenced by genetic and environmental effects. Evidence was found for shared environment effects on the relationship between mother–child warmth and conduct problems. Examining monozygotic twin differences provided further support for non-shared environmental influence on the relationship between mothers’ expressions of hostility and low warmth and adolescent adjustment. Findings are discussed in relation to the interplay between genetic and environmental effects underlying links between parent–child relations and adolescent behavior problems. [ABSTRACT FROM AUTHOR]

Evidence both from psychological research and clinical intervention studies suggests that there are bidirectional influences between overt child behavior problems and parent-child relations. Very little research however, has considered the pattern of relations that exists between Attention Deficit Hyperactivity Disorder (ADHD) and the parent-child relationship within a longitudinal context. Using a longitudinal community sample from the United Kingdom which included 194 school aged children (46% male and 54% female) and both parents, this study examined the relationship between child ADHD symptoms and displays of rejection in the parent-child relationship. These relationships were investigated separately for mothers and fathers using cross-lagged panel correlation and reciprocal effects analysis. Mothers and fathers reported on ADHD symptoms and children reported on their feelings of rejection in the mother-child and father-child relationships. Results suggested differences in the direction of effects linking mother- and father-child rejection and child ADHD symptoms; with ADHD symptoms affecting the mother-child relationship and the converse pattern of effects noted for fathers. Implications for future research focusing on the link between ADHD symptoms and parent-child relationships are discussed. [ABSTRACT FROM AUTHOR]

The present study used a prospective, longitudinal design to investigate genetic and environmental influences on the association between earlier conduct problems and the initiation and progression of marijuana use during adolescence. Parent- and teacher-reported conduct problems assessed at Time 1 (1996) and self-reported marijuana use assessed at Time 2 (2004) were available for 1088 adolescent twin pairs participating in the Cardiff Study of All Wales and North West of England Twins (CaStANET). Using a novel approach to the modeling of initiation and progression dimensions in substance use, findings suggested that the initiation of marijuana use in adolescence was influenced by genetic, common and unique environmental factors. The progression (or frequency) of marijuana use was influenced by genetic and unique environmental factors. Findings for conduct problems indicated that while the presence or absence of conduct problems was largely heritable, the relative severity of conduct problems appeared to be more strongly environmentally influenced. Multivariate model fitting indicated that conduct problems in childhood and early adolescence made a small but significant contribution to the risk for marijuana use 8 years later. [ABSTRACT FROM AUTHOR]

Low birth-weight has been associated with depression and related outcomes in adults, and with problem behaviours in children. This study aimed to examine the association between low birth-weight for gestation and depressive symptoms in children and adolescents and to examine whether the relationship is moderated by genetic risk for depression. An epidemiological, genetically sensitive design was used including 2,046 twins aged 8–17 years (1,023 families). Data were obtained by parental report and analysed using regression analysis. A small but significant association between birth-weight for gestation and early depressive symptoms was observed. The unit increase in depressive symptoms per unit decrease in birth-weight for gestation was greater for individuals at genetic or familial risk for depression. For low birth-weight children, genetic risk for depression moderated the influence of birth-weight for gestation in predicting early depressive symptoms. Birth-weight for gestation is moderated by genetic and familial risk for depression in influencing early depression symptoms. These observations have clinical implications in that the impact of being small for gestational age on depressive symptoms is greater in children at familial/genetic risk although the association between birth weight and depression does not imply causality. [ABSTRACT FROM AUTHOR]

Examines the predisposing factors of antisocial behavior in children with attention deficit hyperactivity disorder (ADHD). Role of genetic factors in the development of antisocial behavior; Definition of ADHD based on symptom scores; Criteria for ADHD symptomatology.

Family studies have shown that maternal depression is a risk factor for depression in children. It is unclear, however, to what extent the familial transmission of depression from mother to child involves genes and how much is due to environmental adversity. This study used an extended twin design to assess the importance of environmental factors in the association of depression in mothers and children while simultaneously accounting for genetic relatedness in a UK. community sample of twins aged 8 to 17 years and their mothers. A model that constrained the genetic and environmental parameters to be equal within the two generations and included genetic and environmental paths between mother and offspring (twins) was tested with data from 1468 families. Significant environmental paths were found when maternal ratings were used. When cross-informant data were used (maternal depression and child self-reports of depression), the environmental path was no longer significant. However, for cross-informant data where children were classified as having high depression scores or scores within the normal range, significant environmental effects were found. These findings are interpreted in light of the strengths and weaknesses of the extended twin and other designs. [ABSTRACT FROM AUTHOR]

There has been much interest in the genetics of attention deficit hyperactivity disorder and molecular genetic studies are now underway. The success of genetic studies will depend on how well the phenotype is defined. Twin studies using parent and teacher rated questionnaires or interviews all appear to yield highly heritable measures. Nevertheless, there is evidence to suggest that parent measures are subject to rater bias. Consequently there has been much interest in obtaining more objective measures of related traits such as attention span and impulsiveness using, computerised neuropsychological tasks. However there have been few twin studies examining the genetic contribution to these neuropsychological measures. The present study aims to investigate whether performance on the Matching Familiar Figures Test (MFFT) and Continuous Performance Task (CPT) is genetically influenced in childhood. 20 monozygotic (MZ) and 20 dizygotic (DZ) twin pairs were randomly selected from the Greater Manchester Twin Register. Preliminary data suggest that MZ twins perform more similarly than DZ twins on the MFFT, but not the CPT. Future work needs to examine whether other neuropsychological measures commonly used in research on ADHD are genetically influenced using larger twin samples. [ABSTRACT FROM AUTHOR]

A correction to this paper has been published: https://doi.org/10.1007/s10519-021-10061-z [ABSTRACT FROM AUTHOR]

Introduction and objective: Some research suggests that children with ADHD are at higher than expected risk of Paediatric Bipolar Disorder (PBD) [1]. No studies have examined the prevalence of PBD in a UK sample of children with ADHD. To examine the prevalence of PBD in children diagnosed with ADHD or Hyperkinetic disorder [2]. Methods: 200 participants with ADHD (170 males, 30 females) aged 6–18 years, mean age = 11.15 years, SD = 2.95, were recruited. Psychopathology including ICD 10 and DSM IV symptoms and diagnoses of PBD was assessed using the Child and Adolescent Psychiatric Assessment (CAPA) research diagnostic interview. Rates of PBD symptoms and diagnoses are reported. Family history of bipolar disorder in parents and siblings was also recorded. Results: Only one child (0.5%), male aged 9 years, met diagnostic criteria for ICD 10 Hypomania and DSM IV Bipolar Disorder Not Otherwise Specified. Discussion: PBD was uncommon in our sample. This varies from findings of some other studies and this may be explained by sample selection, age or differences in diagnostic practices [3]. Conclusion: In a UK sample of children with ADHD, the diagnosis of PBD was uncommon. [ABSTRACT FROM AUTHOR]

A correction notice is presented for the article "White Matter Microstructure Predicts Autistic Traits in Attention-Deficit/Hyperactivity Disorder" by Miriam Cooper, Anita Thapar and Derek K. Jones, which was published online on July 30, 2014.

As genes associated with neuropsychiatric disorders are increasingly identified, we need to progress from observing associations to identifying risk pathways. Investigating intermediate phenotypes, such as cognitive performance, might elucidate such pathways. However there is a need to show that genotype, intermediate phenotype and clinical outcome lie on the same risk pathway [1]. The high activity COMT genotype, in the presence of ADHD is associated with extreme antisocial behavior [2] and in a cohort of 4365 children we test whether two putative intermediate phenotypes, social understanding and executive control lie on the risk pathway. We replicate the COMT high activity genotype association with extreme antisocial behavior (OR = 2.82, 95% CI 2.02, 3.94, p\0.001 for the most severe antisocial behavior). Of the putative intermediate phenotypes, impaired social understanding but not executive control lies on the risk pathway from genotype to antisocial behavior. The findings demonstrate the importance of testing links between genotype, intermediate phenotype and clinical outcome in the same sample to identify potential risk pathways. [ABSTRACT FROM AUTHOR]

Introduction and objective: Maternal smoking during pregnancy is one environmental risk factor which has frequently been observed to be associated with child ADHD symptoms and disorder. Following biologically plausible mechanisms through which exposure to smoking could lead to physiological changes which in turn create risks for ADHD, it is generally assumed that the association between ADHD and smoking during pregnancy is causally mediated. However, it is possible that the observed associations are due to unmeasured genetic or other confounding factors, with some recent studies supporting this supposition (Thapar et al. 2009). Indeed, a recent report by the Royal Academy of Medical Sciences (2007) has highlighted the need to use non-experimental designs to pick apart the causal pathways from risk factors to disorder. It is therefore timely to investigate whether maternal smoking during pregnancy has a true causal influence on offspring ADHD. One way to address this issue is by comparing the risk from maternal and paternal smoking during pregnancy (Davey Smith 2008). If there is a causal intrauterine effect of maternal smoking on child ADHD, no association should be observed between paternal smoking during pregnancy and offspring ADHD. However, if the association is due to genetic or other confounding factors, the risk of offspring ADHD should be of similar magnitudes for maternal and paternal smoking during pregnancy. Methods: We tested this hypothesis in a well characterised longitudinal prospective cohort of UK children, the Avon Longitudinal Study of Parents and Children (ALSPAC). For n = 5,757 children, mothers and biological fathers reported on their own smoking behaviour during pregnancy, whilst ADHD symptoms were assessed using parent and teacher DAWBA reports at age seven years. Associations between maternal and paternal smoking during pregnancy were then compared using regression analyses. Results: Smoking during pregnancy was reported by 27% of mothers and 40% of fathers. Maternal smoking during pregnancy was significantly associated with offspring ADHD symptoms (β = 0.07, t = 4.59, p = 5 9 10-6). Paternal smoking during pregnancy was also associated with increased child ADHD symptoms (β = 0.07, t = 4.73, p = 2 9 10-6) and diagnosis. These associations remained when looking only at paternal smoking in the absence of maternal smoking and did not appear to be the result of exposure to passive smoking. Discussion: In a large prospective cohort, we replicated previously reported associations between maternal smoking during pregnancy and child ADHD. We also found that paternal smoking during pregnancy was also associated with child ADHD to a similar magnitude. These findings suggest, in line with some previous studies (Thapar et al. 2009), that associations between maternal smoking during pregnancy and child ADHD may be due to genetic or other confounding effects, rather than causal intrauterine effects. Conclusion: These findings question previously held assumptions that maternal smoking during pregnancy is a causally mediated risk factor for ADHD and, in line with a recent paper, (Royal Academy of Medical Sciences) highlights the importance of using non-experimental designs to pull apart presumed causal associations. [ABSTRACT FROM AUTHOR]

Emotional problems (anxiety, depression) are prevalent in children, adolescents and young adults with varying ages at onset. Studying developmental changes in emotional problems requires repeated assessments using the same or equivalent measures. The parent-rated Strengths and Difficulties Questionnaire is commonly used to assess emotional problems in childhood and adolescence, but there is limited research about whether it captures a similar construct across these developmental periods. Our study addressed this by investigating measurement invariance in the scales’ emotional problems subscale (SDQ-EP) across childhood, adolescence and early adulthood. Data from two UK population cohorts were utilised: the Millennium Cohort Study (ages 3–17 years) and the Avon Longitudinal Study of Parents and Children (4–25 years). In both samples we observed weak (metric) measurement invariance by age, suggesting that the parent-rated SDQ-EP items contribute to the underlying construct of emotional problems similarly across age. This supports the validity of using the subscale to rank participants on their levels of emotional problems in childhood, adolescence and early adulthood. However strong (scalar) measurement invariance was not observed, suggesting that the same score may correspond to different levels of emotional problems across developmental periods. Comparisons of mean parent-rated SDQ-EP scores across age may therefore not be valid. [ABSTRACT FROM AUTHOR]