123 research outputs found
The relations between DISC-IV DSM diagnoses of ADHD and multi-informant CBCL-AP syndrome scores
Background: Previous studies have examined the relation between attention problems (APs) obtained with the Child Behavior Checklist (CBCL) and attention deficit hyperactivity disorder (ADHD) assessed with the Diagnostic and Statistical Manual of Mental Disorders (DSM). We will examine this relation across sex using multi-informant data. Methods: Parents of 12 538 twins, aged 7, 10, and 12 years, and teachers of twins, aged 10 years, completed the questionnaires. The mothers of a sample of 283 boys and 291 girls who scored either low or high on longitudinal maternal CBCL-AP were interviewed. Results: Children with a low AP score obtained a negative ADHD diagnosis in 96% of cases. Children with a high AP score obtained a positive diagnosis in 36% (girls) and 59% (boys) of cases. The association between paternal and maternal AP ratings and ADHD was the same, whereas the association between teacher AP ratings and ADHD was low. Conclusions: The association between AP and ADHD is higher in boys than girls, possibly because of a bias toward the male manifestation of ADHD. Ā© 2006 Elsevier Inc. All rights reserved
Prenatal and postnatal psychological symptoms of parents and family functioning: the impact on child emotional and behavioural problems
Although relations of various parental psychological problems and family functioning with child development are well documented, it remains unclear whether specific prenatal or specific postnatal risk factors are independently associated with child emotional and behavioural problems, or whether observed associations can be explained by general parental psychopathology. Using a stepwise approach, we examined the effects of prenatal and postnatal parental depressive symptoms, prenatal and postnatal hostility of the parents, as well as prenatal family functioning on the risk of child emotional and behavioural problems. This study was embedded in Generation R: a population-based cohort from foetal life onwards. Mothers and fathers of 2,698 children provided information about depressive symptoms, symptoms of hostility and family functioning during pregnancy and 3Ā years after birth. Mother and father each reported on child behaviour when the child was 3Ā years old. Parental depressive symptoms increased the risk of child emotional and behavioural problems, but this increase was explained by postnatal parental hostile behaviour. Postnatal symptoms of hostility of mothers (ORĀ =Ā 1.34, p valueĀ <0.001) and postnatal symptoms of hostility of fathers (ORĀ =Ā 1.30, p value <0.001) each contributed independently to the risk of child emotional and behavioural problems. Postnatal parental hostility is associated with an increased risk of child emotional and behavioural problems, independent of parental depressive symptoms. These findings suggest that prevention and intervention strategies should focus on psychological symptoms of both mothers and fathers, in particular on hostile behaviour, in families with young children
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Genetic analyses of maternal and teacher ratings on attention problems in 7-year-old Dutch twins
The goal of the present study is to examine genetic and environmental influences on maternal and teacher ratings of Attention Problems (AP) in 7-year-old children. Teachers completed the Teacher Report Form (N=2259 pairs), and mothers the Child Behavior Checklist (N=2057 pairs). Higher correlations were found in twins rated by the same teacher than in twins rated by different teachers. This can be explained by rater bias or by a greater environmental sharing in twins, who are in the same classroom. We further found that 41% of the variation in maternal and teacher ratings is explained by a common factor. The heritability of this common factor is 78%. The heritabilities of the rater specific factors of mothers and teachers are 76% and 39%, respectively. Because Attention Problems that are persistent over situations may indicate more serious behavior problems than context dependent Attention Problems, we believe that gene finding strategies should focus on this common phenotype
Genetic and environmental influences on the relation between attention problems and Attention Deficit Hyperactivity Disorder.
Objective: The assessment of symptoms of ADHD in children is usually based on a clinical interview or a behavior checklist. The aim of the present study is to investigate the extent to which these instruments measure an underlying construct and to estimate the genetic and environmental influences on individual differences in ADHD. Methods: Maternal ratings were collected on 10,916 twins from 5,458 families. Child Behavior Checklist (CBCL) ratings were available for 10,018, 6,565, and 5,780 twins at the ages 7, 10, and 12, respectively. The Conners Rating Scale (4,887 twins) and the DSM interview (1,006 twins) were completed at age 12. The magnitude of genetic and environmental influences on the variance of the three measures of ADHD and the covariance among the three measures of ADHD was obtained. Results: Phenotypic correlations range between .45 and .77. Variances and covariances of the measurements were explained mainly by genetic influences. The model that provided the best account of the data included an independent pathway for additive and dominant genetic effects. The genetic correlations among the measures collected at age 12 varied between .63 and 1.00. Conclusions: The genetic overlap between questionnaire ratings and the DSM-IV diagnosis of ADHD is high. Clinical and research implications of these findings are presented
Assessment and Etiology of Attention Deficit Hyperactivity Disorder and Oppositional Defiant Disorder in Boys and Girls
Attention deficit hyperactivity disorder (ADHD) and oppositional defiant disorder (ODD) are more common in boys than girls. In this paper, we investigated whether the prevalence differences are attributable to measurement bias. In addition, we examined sex differences in the genetic and environmental influences on variation in these behaviors. Teachers completed the Conners Teacher Rating Scale-Revised:Short version (CTRS-R:S) in a sample of 800 male and 851 female 7-year-old Dutch twins. No sex differences in the factor structure of the CTRS-R:S were found, implying the absence of measurement bias. The heritabilities for both ADHD and ODD were high and were the same in boys and girls. However, partly different genes are expressed in boys and girls
A study of genetic and environmental influences on maternal and paternal CBCL syndrome scores in a large sample of 3-year-old Dutch twins.
Background. There is increasing evidence that behavioral problems are common in very young children, yet little is known about the etiology of individual differences in these problems. It is unclear to what degree environmental and genetic factors influence the development of early child psychopathology. In this paper, we focus on the following issues. Firstly, to what degree do genetic and environmental factors influence variation in behavioral problems? Secondly, to what degree are these underlying etiological factors moderated by sex and informant? We investigate these issues by analyzing Child Behavior Checklist (CBCL) data on 9689 3-year-old twin pairs. Methods. Rater Bias and Psychometric Models were fitted to CBCL/2-3 data obtained from mothers and fathers to determine the genetic and environmental contributions to the five CBCL syndromes:aggressive, oppositional, overactive, withdrawn, and anxious/depressed behavior. Results. Parental ratings are influenced by aspects of the child's behavior that are experienced in the same way by both parents and by aspects of the child's behavior that are experienced uniquely by each parent. There is evidence for high genetic contributions to all CBCL syndromes. Shared and non-shared environmental influences play significant roles as well. One exception is overactive behavior, which is influenced by genetic and non-shared environmental influences only. Conclusions. Variation in behavior problems in the very young shows high heritability. Individual raters offer unique perspectives that can have an impact on estimates of problem behavior and genetic architecture. Therefore, multi-informant approaches in the assessment of the very young will be useful to clinicians and researchers alike
The Latent Class Structure of ADHD is stable across informants
Previous studies have looked at the structure of attention-deficit/ hyperactivity disorder (ADHD) using latent class analysis (LCA) of Child Behavior Checklist (CBCL) or Diagnostic and Statistical Manual of Mental Disorders (DSM) symptom structure. These studies have identified distinct classes of children with inattentive, hyperactive, or combined subtypes and have used these classes to refine genetic analyses. The objective of the current report is to determine if the latent class structure of ADHD subtypes is consistent across informant using the Conners' Rating Scales (CRS). LCA was applied to CRS forms from mother, father, and teacher reports of 1837, 1329 and 1048 latency aged Dutch twins, respectively. The optimal solution for boys was a 5-class solution for mothers, a 3-class solution for fathers, and a 4-class solution for teachers. For girls, a 4-class solution for mothers and a 3-class for fathers and teachers was optimal. Children placed into a class by one informant had markedly increased odds ratio of being placed into the same or similar class by the other informants. Results from LCA using Dutch twins with the CRS show stability across informants suggesting that more stable phenotypes may be accessible for genotyping using a multi-informant approach
Ex vivo correction of selenoprotein N deficiency in rigid spine muscular dystrophy caused by a mutation in the selenocysteine codon
Premature termination of translation due to nonsense mutations is a frequent cause of inherited diseases. Therefore, many efforts were invested in the development of strategies or compounds to selectively suppress this default. Selenoproteins are interesting candidates considering the idiosyncrasy of the amino acid selenocysteine (Sec) insertion mechanism. Here, we focused our studies on SEPN1, a selenoprotein gene whose mutations entail genetic disorders resulting in different forms of muscular diseases. Selective correction of a nonsense mutation at the Sec codon (UGA to UAA) was undertaken with a corrector tRNASec that was engineered to harbor a compensatory mutation in the anticodon. We demonstrated that its expression restored synthesis of a full-length selenoprotein N both in HeLa cells and in skin fibroblasts from a patient carrying the mutated Sec codon. Readthrough of the UAA codon was effectively dependent on the Sec insertion machinery, therefore being highly selective for this gene and unlikely to generate off-target effects. In addition, we observed that expression of the corrector tRNASec stabilized the mutated SEPN1 transcript that was otherwise more subject to degradation. In conclusion, our data provide interesting evidence that premature termination of translation due to nonsense mutations is amenable to correction, in the context of the specialized selenoprotein synthesis mechanism
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