Genetic overlap between measures of hyperactivity/inattention and mood in children and adolescents.

OBJECTIVE: Evidence suggests that there is substantial comorbidity between attention-deficit/hyperactivity disorder (ADHD) and major depressive disorder in childhood and adolescence. This study aims to investigate the degree to which etiological factors are shared between the symptoms of these significantly heritable disorders. METHOD: A twin study design was used to determine to what extent the covariation between the traits of ADHD and depression is genetically or environmentally mediated, based on parental reports. A general community sample of 645 twin pairs aged 5 to 17 years from the Cardiff Study of All Wales and North England Twins project took part in the study. Parent-rated measures of hyperactivity/inattention (Abbreviated Conners Hyperactivity subscale) and depression (Short Mood and Feelings Questionnaire). RESULTS: Phenotypes derived from the scales were significantly correlated in both boys and girls. Bivariate structural equation modeling revealed a large overlap in underlying genetic factors (boys, rA = 0.77; girls, rA = 0.67) along with a smaller influence of nonshared environment. CONCLUSIONS: These findings suggest that there are common genes conferring liability to both hyperactive/inattentive and depressive traits in children and adolescents. This has implications for future molecular genetic research into ADHD and major depressive disorder. Additionally, it indicates that the comorbid clinical presentation of these disorders may reflect a common genetic pathway.

The Cardiff Study of all Wales and North West of England Twins (CaStANET): a longitudinal research program of child and adolescent development.

The study of twins and their families provides a highly useful tool for disentangling the genetic and environmental origins of traits. The Cardiff Study of All Wales and North West of England Twins (CaStANET) has followed children and adolescents over time into early adulthood, assessing a wide range of aspects of behavior and psychopathology using self-, parent and teacher reports. Four main waves of data collection have taken place to date, which have provided a wealth of information on the contributions of genetic and environmental risk factors to the psychological health of young people. This article first describes the CaStANET register and subsequently presents some of the findings that have emerged from this resource, with a focus on depression and anxiety, chronic fatigue, attention-deficit/hyperactivity disorder, conduct problems and prosocial behavior. We describe in somewhat more detail the 4th wave of data collection, which has recently been completed and has provided us with extensive information on substance use and problem use as well as associated risk factors in the twins and their families, including longitudinal data on conduct problems and the relations between family members. Because of the wealth of data already collected and the opportunity for genetically informative analyses over time, CaStANET provides a valuable resource for understanding the complexities of the psychological development of young people.

Measuring autistic traits: heritability, reliability and validity of the Social and Communication Disorders Checklist.

BACKGROUND: Autistic traits are widely distributed in the general population, but the boundaries of the autistic spectrum are unclear. Whole-population surveys of unselected samples of children are hampered by the lack of appropriate screening instruments. AIMS: To assess whether the Social and Communication Disorders Checklist (SCDC) fulfils the need for a sensitive measure of autistic traits, which can be completed in a few minutes and which measures heritable characteristics in both males and females. METHOD: A12-item scale, the SCDC, was completed by three independent samples drawn from a twin register, a group with Turner syndrome and children with a diagnosis of autistic-spectrum disorder attending clinics. The data were used to establish the heritability, reliability and validity of the checklist. RESULTS: Traits measured by the SCDC were highly heritable in both genders (0.74). Internal consistency was excellent (0.93) and test - retest reliability high (0.81). Discriminant validity between pervasive developmental disorder and other clinical groups was good, discrimination from non-clinical samples was better; sensitivity (0.90), specificity (0.69). CONCLUSIONS: The SCDC is a unique and efficient first-level screening questionnaire for autistic traits.

Family dysfunction interacts with genes in the causation of antisocial symptoms.

There is emerging evidence of gene-environment interaction effects on conduct problems, both from adoption studies and from a study using a measured genotype. An association between non-violent family dysfunction and conduct problems has also been reported, although not in the context of gene-environment interaction studies. The aim of this study was to examine the interaction of genes and family dysfunction in contributing to conduct problems in young people. Parents of 278 monozygotic and 378 dizygotic twin pairs, aged 5-18, from the CaStANET birth cohort twin register were questioned about zygosity, conduct problems and family environment. Using structural equation modeling we tested for main and interactive effects of genes and family dysfunction modelled as an environmental "moderator variable". Both main and gene-environment interaction effects were highly significant. It was concluded that a risk genotype conferring susceptibility to family dysfunction is responsible for most of the variance in antisocial symptoms in childhood and adolescence.

Do aggressive and non-aggressive antisocial behaviors in adolescents result from the same genetic and environmental effects?

Antisocial behavior (ASB) in adolescents can broadly be separated into two forms; aggressive and non-aggressive. Both are heritable and it has been suggested that aggressive ASB is more heritable. The extent to which genes contribute to the correlation between the two is unknown. Structural equation modeling was applied to a population-based twin sample of 258 twins pairs aged 11-18 to estimate the heritability of each form of ASB and to estimate the extent to which the phenotypic correlation was the consequence of shared genes and environmental factors. Non-shared environment and genetic factors substantially influenced both forms of ASB. The heritability of aggressive (but not non-aggressive) ASB was significantly higher in girls than in boys. Combining both sexes, a model in which the genetic effects on aggressive and non-aggressive ASB were identical could be rejected. Our results suggest a partial genetic overlap with a specific genetic effect contributing to the variance of aggressive ASB and a stronger genetic effect on aggression in females than in males.

The development of prosocial behaviour in children and adolescents: a twin study.

BACKGROUND: Childhood psychopathology is associated with both high and low levels of prosocial behaviour. It has been proposed that the development of prosocial behaviour shows emerging and consolidating individual differences as children grow older. The influences on these individual differences have not previously been examined in children and adolescents using multiple raters in a genetically informative design. METHODS: Twin data from 682 families based on parent and teacher reports were used to examine the genetic and environmental influences on prosocial behaviour in 5-16-year-olds. Effects of sex, age and rater were examined. RESULTS: There were no significant differences in the magnitude of genetic and environmental influence on male and female prosocial behaviour. Declining common environment and increasing genetic influences were seen with age. This emerged as a trend in parent data and reached statistical significance in teacher data. When parent and teacher data were examined together in a rater bias model significant bias acting on the parent ratings emerged, in keeping with previous discrepancies between parental and observational measures. There was overlap in the phenotype rated by parents and teachers, with a highly heritable common underlying phenotype. CONCLUSIONS: The influences on the distribution of prosocial behaviour in children and adolescents show declining shared environmental and increasing genetic influences with age. Parental assessments of prosocial behaviour show significantly higher scores than teacher reports and whilst there is overlap in the phenotype rated by parents and teachers, parents show significant bias in their ratings.

Prevalence of chronic disabling fatigue in children and adolescents.

BACKGROUND: The epidemiology of chronic fatiguing illnesses in young people is poorly understood. AIMS: To estimate the lifetime prevalence of different definitions of chronic fatigue in 8- to 17-year-olds. METHOD: Participants came from two population-based twin series. Parents completed self-report questionnaires that inquired whether either child had ever experienced more than a few days of disabling fatigue. Telephone interviews were undertaken for individuals who had experienced such an episode. RESULTS: Questionnaires were returned by 1468 families (65% response rate) and telephone interviews were undertaken regarding 99 of the 129 subjects (77%) who had experienced fatigue. The lifetime prevalence estimates ranged from 2.34% (95% CI 1.75-2.94) for disabling fatigue lasting 3 months to 1.29% (95% CI 0.87-1.71) for a disorder resembling adult operationally defined chronic fatigue syndrome. CONCLUSIONS: From the age of 11 years, young people have similar rates and types of chronic fatiguing illnesses to adults.

Conduct problems in children and adolescents: a twin study.

BACKGROUND: Evidence supports a genetic influence on conduct problems as a continuous measure of behavior and as a diagnostic category. However, there is a lack of studies using a genetically informative design combined with several different informants and different settings. OBJECTIVES: To examine genetic and environmental influences on conduct problems rated by parent and teacher reports and self-reports and to determine whether their ratings reflect a common underlying phenotype. DESIGN: A twin study design was used to examine conduct problem scores from ratings by teachers, parents, and twins themselves. SETTING: General community. PARTICIPANTS: Twins aged 5 to 17 years participating in the Cardiff Study of All Wales and North England Twins (CaStANET) project. MAIN OUTCOME MEASURES: Conduct problem scale from the Strengths and Difficulties Questionnaire. RESULTS: Conduct problem scores were significantly heritable based on parent and teacher reports and self-reports. Combining data from all 3 informants showed that they are rating a common underlying phenotype of pervasive conduct problems that is entirely genetic, while teacher ratings show separate genetic influences that are not shared with other raters. CONCLUSIONS: Conduct problems are significantly heritable based on parent and teacher reports and self-reports, and are also influenced by environmental effects that impinge uniquely on children from the same family. There is a cross-situational conduct problems' phenotype, underlying the behavior measured by all informants, that is wholly genetic in origin. No significant influence of shared environmental effects was found.

The genetic relationship between social cognition and conduct problems.

Studies of children and adolescents with conduct problems suggest both genetic and environmental influences on population variance. Any genetic influence is likely to be complex and to act via mediating attributes of personality or cognitive style. One potential mediating attribute is social cognitive ability, as conduct problems have been shown to be associated with deficient social cognitive skills. The current investigation has examined the correlation between conduct problems and social cognition and has investigated the genetic and environmental influences on these measures and their covariation using a twin design. A population-based sample of twins aged 5-17 was used to examine the genetic relationship between conduct problems and social cognition using parent-report questionnaires. Conduct problems and social cognition were found to be highly correlated and to share common genetic influences that accounted for about half the covariation in scores. Each phenotype was subject to its own environmental influences that were not shared.

Maternal smoking during pregnancy and attention deficit hyperactivity disorder symptoms in offspring.

OBJECTIVE: The aim of this study was to examine whether smoking during pregnancy is associated with symptoms of attention deficit hyperactivity disorder (ADHD) in offspring and whether these effects are additional to genetic influences. METHOD: Children's ADHD symptoms (parent- and teacher-rated), maternal smoking during pregnancy, conduct disorder symptoms, and family adversity were assessed with questionnaires for a population-based sample of twins (1,452 twin pairs 5-16 years of age). RESULTS: Although genetic influences accounted for most of the variance in offspring ADHD, maternal smoking during pregnancy was still found to show a significant environmentally mediated association. Maternal smoking remained a significant influence when other potential confounds were taken into account. CONCLUSIONS: Maternal smoking during pregnancy appears to show an association with offspring ADHD symptoms that is additional to the effects of genes and not attributable to shared rater effects, clinical referral biases, or covariation with antisocial behavior.

Depressive symptoms in children and adolescents: changing aetiological influences with development.

BACKGROUND: Evidence suggests that depressive symptoms become increasingly heritable as children grow into adolescence. However, the literature is not entirely consistent in this respect and existing longitudinal twin studies have examined changes within adolescence only. METHOD: Parent and self-report questionnaire data were used to examine the genetic and environmental influences on depressive symptoms in a UK sample of 670 twin pairs aged 5-17. Age effects were examined cross-sectionally and longitudinally using data collected over a 3-year period. RESULTS: Cross-sectional analyses showed that shared environmental effects had significant influence in younger children but not in adolescence, when depression scores were significantly more heritable. The results of these cross-sectional analyses were supported when two waves of parent-report data collected over three years were analysed. Significant new genetic influences emerged in adolescence but no new shared environmental influences. Some sex differences were found, with girls showing greater genetic influence than boys, but only from parent-report data. CONCLUSIONS: These findings support and extend earlier work which has shown increasing genetic influence on depressive symptoms as children grow into adolescence.

The Aberfan disaster: 33-year follow-up of survivors.

BACKGROUND: Experiencing life-threatening events often contributes to the onset of such psychiatric conditions as post-traumatic stress disorder (PTSD). Children can develop PTSD; however, there is controversy over whether PTSD symptoms decrease or persist over time. AIMS: To examine the long-term effects of surviving the 1966 Aberfan disaster in childhood. METHOD: Survivors (n=41) were compared with controls (n=72) matched for age and background. All were interviewed using the Composite International Diagnostic Interview, measures of current health and social satisfaction, and the General Health Questionnaire. The survivor group also completed the Impact of Event Scale to assess current levels of PTSD. RESULTS: Nineteen (46%; 95% CI 31-61) survivors had had PTSD at some point since the disaster, compared with 12 (20%; 95% CI 10-30) controls (OR=3.38 (95% CI 1.40-8.47)). Of the survivors,12 (29%; 95% CI 15-43) met diagnostic criteria for current PTSD. Survivors were not at a significantly increased risk of anxiety, depression or substance misuse. CONCLUSIONS: Trauma in childhood can lead to PTSD, and PTSD symptoms can persist for as long as 33 years into adult life. Rates of other psychopathological disorders are not necessarily raised after life-threatening childhood trauma.

Attitudes towards future testing for bipolar disorder susceptibility genes: a preliminary investigation.

The discovery of susceptibility genes for the major psychiatric illnesses may lead to the development of presymptomatic and prenatal tests. In a preliminary study we assessed the attitudes of 147 bipolar patients, 90 attendees at their family doctor (GP) and 32 psychiatrists to the possible development of genetic tests for bipolar disorder susceptibility genes. Our results suggest that patients and the public will look favourably on the development of presymptomatic (but not prenatal) testing for bipolar disorder susceptibility genes. Psychiatrists, who will have to administer such tests, appear significantly more cautious.

Observer effects and heritability of childhood attention-deficit hyperactivity disorder symptoms.

BACKGROUND: Twin studies have found that childhood attention-deficit hyperactivity disorder (ADHD) has a strong genetic component. Estimates of heritability, the extent of non-additive genetic effects and of 'sibling contrast' effects vary between different studies. AIMS: To use multiple informants to assess the extent to which observer effects influence such estimates in an epidemiological sample of twins. METHOD: Questionnaire packs were sent to the families and teachers of twins aged 5-16 years in the Bro Taf region of South Wales. The twins were ascertained from community paediatric registers. RESULTS: Both parent- and teacher- rated data showed a high degree of heritability for ADHD measured as a symptom dimension, but the correlation between the two types of rater was modest. Bivariate analyses suggested that parent and teacher ratings reflect the effects of different genes. Self-report data from twins aged 11-16 years showed no evidence of genetic effects. CONCLUSIONS: Although ADHD is shown to be highly heritable by both parent- and teacher-rated data, the underlying genotypes may be substantially different. This has implications for study designs aiming to find genes that contribute to the disorder.